Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers for Treating Essential Hypertension

  1. David B. Matchar, MD;
  2. Douglas C. McCrory, MD, MHS;
  3. Lori A. Orlando, MD, MHS;
  4. Manesh R. Patel, MD;
  5. Uptal D. Patel, MD;
  6. Meenal B. Patwardhan, MD, MHSA;
  7. Benjamin Powers, MD;
  8. Gregory P. Samsa, PhD; and
  9. Rebecca N. Gray, DPhil
  1. From Duke Center for Clinical Health Policy Research, Duke Clinical Research Institute, Duke University, and the Center for Health Services Research in Primary Care, Durham U.S. Department of Veterans Affairs Medical Center, Durham, North Carolina.
     
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    Abstract

    Background: The relative effectiveness of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) for lowering blood pressure is unknown.

    Purpose: To compare the benefits and harms of ACE inhibitors versus ARBs for treating essential hypertension in adults.

    Data Sources: MEDLINE (1966 to May 2006), the Cochrane Central Register of Controlled Trials (Issue 2, 2006), and selected reference lists were searched for relevant English-language trials. The MEDLINE search was updated to August 2007 to identify head-to-head trials that reported blood pressure outcomes and major cardiovascular events.

    Study Selection: 61 clinical studies that directly compared ACE inhibitors versus ARBs in adult patients with essential hypertension, reported an outcome of interest, lasted at least 12 weeks, and included at least 20 patients.

    Data Extraction: A standardized protocol with predefined criteria was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality and applicability; and assess the strength of the body of evidence for key outcomes.

    Data Synthesis: ACE inhibitors and ARBs had similar long-term effects on blood pressure (50 studies; strength of evidence, high). No consistent differential effects were observed for other outcomes (few studies reported long-term outcomes), including death, cardiovascular events, quality of life, rate of single antihypertensive agent use, lipid levels, progression to diabetes, left ventricular mass or function, and kidney disease. Consistent fair- to good-quality evidence showed that ACE inhibitors were associated with a greater risk for cough. There were fewer withdrawals due to adverse events and greater persistence with therapy for ARBs than for ACE inhibitors, although this evidence was not definitive. Patient subgroups for whom ACE inhibitors or ARBs were more effective, associated with fewer adverse events, or better tolerated were not identified.

    Limitations: Few studies involved a representative sample treated in a typical clinical setting over a long duration, treatment protocols had marked heterogeneity, and substantive amounts of data about important outcomes and patient subgroups were missing.

    Conclusion: Available evidence shows that ACE inhibitors and ARBs have similar effects on blood pressure control, and that ACE inhibitors have higher rates of cough than ARBs. Data regarding other outcomes are limited.

    Editors' Notes

    Context

    • Are angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) more effective for treating essential hypertension?

    Contribution

    • This systematic review of trials that directly compared ACE inhibitors and ARBs in adults with essential hypertension found good evidence that the agents had similar long-term effects on blood pressure. There were no consistent differential effects for mortality, cardiovascular events, progression to diabetes, left ventricular function, or kidney disease. Cough was more frequent with ACE inhibitors than ARBs.

    Implication

    • Both ACE inhibitors and ARBs have similar effects on blood pressure and may not have differential effects on other clinical outcomes, although ACE inhibitors do cause cough more often than ARBs.

    —The Editors

    More than 65 million U.S. adults—approximately one third—have hypertension. In addition to being the leading attributable risk factor for death throughout the world (1), hypertension results in substantial illness due to its effect on several target organs, including the brain, eyes, heart, arteries, and kidneys.

    Despite the high rate of morbidity and mortality attributable to hypertension, control remains suboptimal (2). In addition to several effective nonpharmacologic interventions, many individuals require antihypertensive medication to lower blood pressure and often require several medications together (2). Among the most common of the many choices in antihypertensive therapy are those aimed at inhibiting the renin–angiotensin–aldosterone (renin) system. Currently, renin system inhibitors include angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs).

    Although clinicians regard ACE inhibitors and ARBs as effectively equivalent, it is not clear whether this is appropriate. For example, ACE inhibitors do not entirely block production of angiotensin II because of other, unaffected converting enzymes. Also, ACE inhibitors are associated with well-known adverse events not shared by ARBs, including cough (estimated incidence, 5% to 20%) and the possibly related phenomenon of angioedema (estimated incidence, 0.1% to 0.2%) (3). Although both ACE inhibitors and ARBs are highly effective in lowering blood pressure among patients with essential hypertension (4, 5), their comparative effectiveness and the relative advantages and disadvantages of ACE inhibitors versus ARBs are unknown.

    This review summarizes the evidence on the comparative long-term benefits and harms of ACE inhibitors versus ARBs for treating essential hypertension in adults. The full technical report was commissioned by the Agency for Healthcare Research and Quality (6).

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    Methods

    We developed and followed a standardized protocol for all steps of the review.

    Data Sources and Searches

    We searched MEDLINE (1966 to week 3 of May 2006) and the Cochrane Central Register of Controlled Trials (Issue 2, 2006) for studies published in English after 1988, using terms for drug interventions, hypertension, and study design. We also reviewed bibliographies submitted by pharmaceutical companies to the Scientific Resource Center for the Agency for Healthcare Research and Quality's Effective Health Care Program, reference lists of relevant review articles, and citations identified by reviewers of the draft report. For the current review, we updated our MEDLINE search to August 2007 to identify new head-to-head trials that reported blood pressure outcomes and major cardiovascular events. Results from the newly identified studies (7–21) were consistent with the evidence described in the full technical report and are not presented here.

    Study Selection

    We included comparative clinical studies of any design (including randomized, controlled trials and nonrandomized, controlled trials; cohort studies; and case–control studies) that provided direct comparisons of ACE inhibitors versus ARBs at 12 weeks or more after the initial intervention. In addition to simple comparisons of a single ACE inhibitor versus a single ARB, we included studies with “grouped” comparisons (such as a specific ARB versus “ACE inhibitors” or unspecified “ARBs” versus unspecified “ACE inhibitors”) and comparisons in which the same drug was administered with an ACE inhibitor versus that drug with an ARB (for example, losartan and hydrochlorothiazide vs. enalapril and hydrochlorothiazide). We excluded studies with comparisons in which the drugs administered with an ACE inhibitor differed from those administered with an ARB (for example, enalapril and manidipine vs. irbesartan and hydrochlorothiazide). We included studies with treatment protocols that permitted the addition of other antihypertensive medications during the trial, provided that the co-intervention protocols were the same in the ACE inhibitor and ARB treatment groups. Outcomes we considered included blood pressure control, adherence, quality of life, several intermediate outcomes, and harms. We excluded studies with fewer than 20 total patients in the ACE inhibitor and ARB treatment groups and focused on studies of adults (≥18 years of age) with essential hypertension, as defined by the study authors.

    We also evaluated studies of ARBs versus other (non–ACE inhibitor) comparators and ACE inhibitors versus other (non-ARB) comparators, which were to be considered in case too few direct head-to-head trials were identified for outcomes of interest. Appendix 1 contains the details of how we identified and reviewed indirect comparison studies.

    Data Extraction and Quality, Applicability, and Strength of Evidence Assessments

    One author extracted data from each study, which were confirmed by another author. Extracted information included study design; interventions; population characteristics; recruitment setting; inclusion and exclusion criteria; numbers of participants screened, eligible, enrolled, and lost to follow-up; and results for each outcome.

    We used predefined criteria adapted from those developed by the U.S. Preventive Services Task Force (22) and the Centre for Reviews and Dissemination in the United Kingdom (23) to assess the quality of individual studies as good, fair, or poor, and we noted important limitations on internal validity for studies rated as fair or poor. The applicability of individual studies was assessed by noting the most important potential limitations (up to 3) in a study's applicability from among the list described by Rothwell (24), as adapted by the Scientific Resource Center (Appendix 2). Quality and applicability assessments are detailed for individual studies in the evidence tables included in the full report (6). Finally, we assessed the strength of the body of evidence for each key question as high, moderate, low, or very low by using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework (25).

    Data Synthesis and Analysis

    Given that many studies did not have the statistical power to determine equivalence for relevant outcomes, we considered pooling (without regard to the specific drug within the ACE inhibitor or ARB class) to overcome a type II error. In evaluating direct comparison studies for potential data synthesis, we primarily considered clinical homogeneity. In general, we considered groups of studies as suitable for quantitative synthesis when we identified at least 4 clinically and relatively similar studies that assessed the same outcome. We used additional and more detailed criteria to determine suitability for pooling of indirect comparisons, as such comparisons are tenuous (Appendix 1). We did not attempt to pool direct and indirect comparison studies in a single analysis, primarily because we did not identify a sufficient number of clinically similar indirect comparison studies to analyze.

    When we pooled studies, we used the random-effects model for the primary analysis and the fixed-effect model for sensitivity analysis. We stratified analyses by study design, separating randomized, controlled trials from observational studies. We performed all analyses by using Comprehensive Meta-analysis, version 2 (Biostat, Englewood, New Jersey). For count outcomes, we calculated summaries of the relative effect (odds ratios) and absolute effect (risk difference). We chose the Peto method for analyzing data on cough and withdrawals due to adverse events because event rates were low and treatment groups were not substantially imbalanced, conditions under which this method is the least biased and most powerful (26). This method also allows inclusion of studies with zero events in 1 group with no continuity correction. For data on rates of successful monotherapy, we used risk differences because event rates were high, which makes the assumption of a constant odds ratio unreasonable.

    Role of the Funding Source

    The Agency for Healthcare Research and Quality formulated the initial study questions and reviewed and commented on planned methods, data analysis, and the draft report. The funding source did not participate in the search of the literature, determination of study eligibility, or evaluation of individual studies.

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    Results

    Of 1185 citations, 69 reports (61 distinct studies) directly compared ACE inhibitors with ARBs (Figure 1). Forty-seven studies were randomized, controlled trials; 1 was a nonrandomized, controlled trial; 9 were retrospective cohort studies; 2 were prospective cohort studies; 1 was a cross-sectional cohort study; and 1 was a case–control study. Table 1 shows the numbers of studies that compared different agents. Enalapril was the most frequently studied ACE inhibitor (24 studies), and losartan the most frequently studied ARB (19 studies). Most studies were relatively short-term; 19 followed patients for 12 weeks, and 21 followed patients between 12 weeks and 6 months. Most studies excluded patients with secondary causes of hypertension, as well as patients with recent acute events, such as myocardial infarction or stroke. Table 2 summarizes the number and quality scores of reviewed studies, by outcome assessed.

    Figure 1.
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      Figure 1. Study flow diagram.

      *See Appendix 1. ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker.

      View this table:
      Table 1. Number of Included Studies and Publications Evaluating Various Treatment Comparisons*
      View this table:
      Table 2. Summary of Reviewed Studies*

      Comparative Effectiveness for Controlling Blood Pressure and Improving Cardiovascular Outcomes and Risk

      Angiotensin-converting enzyme inhibitors and ARBs seem to have similar long-term effects on blood pressure in individuals with essential hypertension.

      Because there were too few deaths or major cardiovascular events in the included studies, we could not discern any differential effect of ACE inhibitors versus ARBs for these critical outcomes. Likewise, ACE inhibitors and ARBs exhibited no consistent differential effects on several potentially important risk factors, including lipid levels, progression to type 2 diabetes mellitus, markers of carbohydrate metabolism or diabetes control, measures of left ventricular mass or function, and progression of renal disease (based on creatinine level, glomerular filtration rate, or proteinuria). Relatively few studies assessed these outcomes over the long term.

      Blood Pressure Control

      Of the 50 identified studies that reported blood pressure control, 47 were randomized, controlled trials. These studies had substantial protocol differences, including maximal medication dose, whether additional blood pressure medications were permitted, whether adjustments were by algorithm or physician discretion, whether nonresponders were withdrawn, and whether blood pressure was reported as a change or only as final blood pressure. Thirty-seven studies (42 articles) reported no statistically significant differences in blood pressure control (27–68), 2 studies (3 articles) favored ACE inhibitors (69–71), 8 studies favored ARBs (72–79), and 3 studies did not report the comparison between the agents (80–82). Both studies favoring ACE inhibitors compared 50 mg of losartan with 20 mg of enalapril, in contrast to other studies showing no difference between these 2 agents, which compared 100 mg of losartan with 10 or 20 mg of enalapril. For studies that favored ARBs, we found no salient features of the study design that might explain the difference. Notably, across studies, the modal difference in systolic or diastolic blood pressure was 0 mm Hg and generally did not exceed 4 mm Hg.

      Success as a Single Antihypertensive Agent

      We identified 22 studies (27, 34, 37, 42–44, 46, 47, 49, 53, 55, 58–60, 66–69, 73, 80, 82, 83) that reported successful monotherapy. The definition of “successful” differed across studies. Definitions included various systolic or diastolic blood pressure cutoffs or lack of additional antihypertensive medication at the end of the study. The rates of successful monotherapy ranged between 6% and 93% (median, 61%). The average proportion of patients who achieved successful monotherapy across all studies was about 55% for both ACE inhibitors and ARBs.

      Figure 2 shows estimates for the differences between ACE inhibitors and ARBs in the proportion of patients achieving successful blood pressure control with a single agent. We found no important statistical heterogeneity for these estimates (Q statistic = 25.8; I2 = 18%; P = 0.22). The summary estimate using a random-effects model was 1.3% (95% CI, −1.0% to 3.5%; P = 0.26). Results based on odds ratios and median incidence were similar.

      Figure 2.
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        Figure 2. Successful monotherapy: angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs).

        The first group is observational studies and the second group is randomized, controlled trials.

        Because the definition of successful control of blood pressure with a single agent requires that a patient continue the originally prescribed drug regimen and receive no additional antihypertensive agent, successful monotherapy reflects both the efficacy of the medication and tolerability and adherence to the prescribed therapy. The tendency in favoring ARBs for this outcome seemed driven primarily by differences in tolerability and adherence. The observed benefit of ARBs seemed heavily influenced by retrospective cohort studies, in which medication discontinuation rates were higher in ACE inhibitor–treated patients, and by randomized, controlled trials that had loosely defined protocols for medication titration and switching.

        Death and Major Cardiovascular Events

        Only 9 studies, described in 13 publications (27, 29, 31, 38, 41, 44, 46, 48, 49, 59, 62, 65, 79), reported how many patients died or had myocardial infarction or stroke (Table 2). Most of these studies excluded patients with clinically significant cardiovascular disease and other comorbid conditions. Of 3322 patients who received an ACE inhibitor or an ARB in these studies, 16 died; 12 of these were from a study by Barnett and colleagues (29). That study provided the most and the longest-term data on cardiovascular events, evaluating telmisartan (n = 120) versus enalapril (n = 130) in patients with type 2 diabetes and early nephropathy over a 5-year treatment period. Event rates were similar in this higher-risk sample, with stroke, congestive heart failure, nonfatal myocardial infarction, or death occurring in 31 patients receiving telmisartan (25.8% [CI, 18.3% to 34.6%]) and 25 patients receiving enalapril (19.2% [CI, 12.9% to 27.1%]). In none of the studies did investigators attribute any observed events directly to therapy.

        Lipid Levels and Glucose Control

        Eleven randomized, controlled trials (36, 38–40, 42, 44, 46, 58, 62, 67, 70) and 1 observational case–control study (68) reported lipid levels. We rated most of these studies as fair quality. None addressed the use of lipid-lowering agents during the study. Nine studies found no change either between or within groups in total cholesterol, low-density lipoprotein, high-density lipoprotein, or triglyceride levels during the study. The remaining 3 studies detected a small but statistically significant change within the groups in total cholesterol (44, 46), low-density lipoprotein (36), and triglyceride levels (44). The magnitude of these changes was equivalent for the compared medications except for 1 of the total cholesterol studies (44), which favored the ARB, and the low-density lipoprotein study (36), which favored the ACE inhibitor.

        Thirteen studies measured glucose or hemoglobin A1c. All but 2 (28, 68) were randomized, controlled trials. We rated 2 as good quality (36, 62), 7 as fair quality (38–40, 46, 53, 67, 70), and 4 as poor quality (28, 42, 44, 68). None addressed hypoglycemic therapy during the study. No change occurred in hemoglobin A1c either between or within groups in 11 studies. One reported a small decrease in glucose that was statistically greater in the ACE inhibitor group (36), and 1 reported a statistically significant but clinically unimportant increase in hemoglobin A1c for both groups (46). Results were similar between the 6 studies that specifically included diabetic patients and the studies that did not.

        Left Ventricular Mass or Function

        Eight studies presented results on left ventricular mass or function assessed by left ventricular mass index (28, 35, 68), left ventricular ejection fraction (32, 61), or both (34, 57, 65). Half of these studies had fewer than 50 patients (28, 35, 61, 65), whereas the other half had 100 or more patients (32, 34, 57, 68). All but 2 (28, 68) were randomized, controlled trials. Two had relatively long-term follow-up (≥3 years) (35, 68), 5 had between 6 and 12 months of follow-up (28, 32, 34, 57, 65), and 1 had only 3 months of follow-up (61). Despite differences in sample size, study design, length of follow-up, study quality, therapeutic agents, and outcome measure, most of the studies demonstrated either similar differences in improvements in left ventricular mass or function, with an approximately 2% difference between the ACE inhibitor and ARB groups (28, 34, 65, 68), or no change in these measures for either group (35, 57).

        Serum Creatinine Level, Glomerular Filtration Rate, and Proteinuria

        Twenty studies identified renal outcomes. We excluded 1 of these studies (65) from our analysis because no changes would be expected in the outcome assessed (serum creatinine) in the sample studied (patients with end-stage renal disease who had been receiving maintenance hemodialysis for ≥1 month). Of the remaining 19 studies, 9 assessed either serum creatinine or glomerular filtration rate (28, 35, 38, 39, 52, 63, 67, 68, 78), 4 assessed proteinuria (36, 53, 62, 84), and 6 assessed both (29, 44, 46, 50, 58, 70).

        The 15 studies that described changes in creatinine level or glomerular filtration rate did not consistently demonstrate differential effects related to renal function with the use of ACE inhibitors versus ARBs. Among the 9 studies that reported data on renal function, none was rated as good quality, 4 were of poor quality (28, 44, 63, 68), 2 were not randomized, controlled trials (28, 68), and only 2 had more than 100 patients (29, 52). All but 2 (29, 52) compared losartan with a specific ACE inhibitor. The most frequently studied ACE inhibitor was enalapril (28, 29, 35, 63, 68). The 10 studies that described changes in urine albumin level or protein excretion consistently were of fair quality and demonstrated no differential effects between ACE inhibitors and ARBs related to the reduction of urinary protein or albumin excretion among patients with essential hypertension.

        Quality of Life, Adverse Events, Persistence, and Adherence

        On the basis of 4 studies, 2 of which did not provide quantitative data, we found no differences in measures of general quality of life. Angiotensin-converting enzyme inhibitors have been consistently shown to be associated with a greater risk for cough than ARBs (Peto pooled odds ratio, 0.32). For randomized, controlled trials, this translates to a difference in rates of cough of 6.7%; however, for cohort studies with lower rates of cough, this translates to a difference of 1.1%. We found no evidence of differences in rates of other commonly reported specific adverse events. Angioedema was reported only in patients treated with ACE inhibitors; however, because angioedema was rarely explicitly reported in the included studies, we could not estimate its frequency in this population. Pill counts indicated that rates of adherence to ACE inhibitors and ARBs were similar; this result may not be applicable outside the clinical trial setting. Rates of continuation with therapy seem to be somewhat better with ARBs than with ACE inhibitors; however, the precise magnitude of this effect is difficult to quantify.

        Quality of Life

        Four fair-quality studies described in 8 papers reported quality-of-life outcomes (27, 31, 35, 38, 41, 43, 48, 76). They used a variety of quality-of-life scales. None demonstrated a differential effect on quality of life between ACE inhibitors and ARBs.

        Serious and Overall Adverse Events

        Seven studies of either fair or good quality (43, 49, 52, 58, 74, 78, 79) reported overall rates of serious adverse events. The biggest issues in evaluating these studies were inconsistent reporting and a low rate of serious adverse events (0% to 6%). A potentially salient and serious adverse event, angioedema, was reported in only 3 of the 61 included studies (43, 51, 55). All reported cases occurred in patients treated with an ACE inhibitor. Because angioedema was rarely explicitly reported in the included studies, we could not estimate its frequency.

        Of the 29 studies that reported overall adverse event rates (29, 30, 33, 34, 36–38, 43, 45, 47, 49, 51, 52, 55, 58, 59, 63, 66, 69, 70, 72–79, 81), 20 were assessed as being fair quality and 5 as poor quality. The manner in which adverse events were reported substantially varied. Depending on the definition used, adverse event rates ranged from 0% to 100% (median, 32%) for ACE inhibitors and 0% to 96% (median, 28%) for ARBs.

        Specific Adverse Events

        Thirty studies reported rates of 1 or more specific adverse events (30, 33–36, 38, 43, 45–47, 49, 51, 52, 54, 55, 59, 66, 69, 70, 72–79, 84–86), including cough (29 studies); headache (21 studies); dizziness (18 studies); fatigue (10 studies); upper respiratory infection (6 studies); nausea (6 studies); viral infection, ankle edema, and back pain (3 studies each); and palpitations, myalgia, diarrhea, malaise, and hypotension (2 studies each). Several other adverse events were reported in 1 study, including pharyngitis, rhinitis, dyspnea, abdominal pain, urinary tract infection, constipation, dry mouth, feeling sick, pyrosis, insomnia, musculoskeletal pain, flatulence, epigastric discomfort, increased sweating, and erythematous rash.

        Given the large number of commonly reported specific adverse events, we focused on 3 that had the largest difference in absolute rates across studies: headache, dizziness, and cough.

        Headache.

        Twenty-one studies compared headache in patients treated with ACE inhibitors and ARBs. Rates of headache ranged from 1% to 22% for ARB-treated groups (overall rate, 6.3%) and from 0% to 34% in ACE inhibitor–treated groups (overall rate, 7.9%). Meta-analyses did not reveal evidence of a differential effect of ACE inhibitors and ARBs on headache.

        Dizziness.

        Eighteen studies compared dizziness in patients treated with ACE inhibitors and ARBs. Rates of dizziness ranged from 1% to 20% for ARB-treated groups (overall rate, 4.3%) and from 0% to 18% in ACE inhibitor–treated groups (overall rate, 5.4%). Meta-analyses did not reveal evidence of a differential effect of ACE inhibitors and ARBs on dizziness.

        Cough.

        Twenty-nine studies compared cough in patients treated with ACE inhibitors and ARBs (30, 33–36, 38, 43, 45–47, 49, 51, 52, 54, 55, 59, 66, 69, 70, 72–74, 76–79, 84–86). We rated 4 of these studies as good, 20 as fair, and 5 as poor in quality. Rates of cough ranged from 0% to 13% for ARB-treated groups (mean, 3%; median, 1%) and from 0% to 23% in ACE inhibitor–treated groups (mean, 10%, median, 9%). All 29 studies demonstrated higher rates of cough in ACE inhibitor–treated participants. For the meta-analysis of studies reporting cough as an adverse event, we included all 29 studies that reported cough rates (Figure 3). The Cochran Q test and the I2 between studies demonstrated statistical heterogeneity among the studies (Q statistic = 57.5; I2 = 51.3%). The observed rates of cough were much higher in randomized, controlled trials, in which patients were queried systematically for the symptom, than those in cohort studies. The rates of cough in randomized, controlled trials were 9.9% for the ACE inhibitor group and 3.2% for the ARB group (absolute risk difference, 6.7 percentage points), whereas the rates of cough in cohort studies were 1.7% for the ACE inhibitor group and 0.6% for the ARB group (absolute risk difference, 1.1 percentage points).

        Figure 3.
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          Figure 3. Cough as an adverse event: angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs).

          The first group is observational studies and the second group is randomized, controlled trials.

          Withdrawals Due to Adverse Events

          Twenty-four studies (28–30, 33–35, 38, 43, 45, 46, 49, 51–55, 62, 63, 66, 68, 70, 72, 75, 78) reported withdrawals due to adverse events. We rated 2 as good in methodological quality, 18 as fair, and 4 as poor. Rates of withdrawal due to adverse events ranged from 1% to 41% (mean, 10%; median, 3%) for patients who received ARBs and 1% to 41% (mean, 19%; median, 8%) for patients who received ACE inhibitors. Sixteen studies demonstrated higher withdrawal rates in ACE inhibitor–treated participants, 3 demonstrated higher rates in ARB-treated participants, and 5 showed no difference in rates (Figure 4). The differences in rates of adverse events (such as cough) and the duration of the trials probably explain this heterogeneity. We found modest statistical heterogeneity between studies (Q statistic = 36.0; I2 = 36.2%). The Peto summary odds ratio favored ARBs (0.51 [CI, 0.38 to 0.70]; random-effects model). Given this odds ratio and a median withdrawal rate of 8% for ACE inhibitors, the expected withdrawal rate for ARBs is 3.7%.

          Figure 4.
          View larger version:
            Figure 4. Withdrawals due to adverse events: angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs).

            The first group is observational studies and the second group is randomized, controlled trials.

            Caveats regarding these data are that only 1 study was of good methodological quality and reporting of withdrawal data varied greatly.

            Adherence and Persistence

            Seventeen studies described in 19 papers (33, 45, 51, 58, 60, 72, 76, 79, 80, 83, 87–95) reported quantitative information on persistence or adherence. We operationally defined adherence as the consistency with which medication was taken, measured by such direct evidence as pill counts. Collecting such evidence typically requires an experimental setting; this limits the ability to generalize because patients who participate in trials and are aware that they are being observed will probably demonstrate better adherence than those in usual practice. Adherence for both ACE inhibitors and ARBs was high (>90%).

            We operationally defined persistence as the percentage of patients continuing a particular therapy after a certain period (for example, patients continuing ARB therapy 12 months after the initial prescription), where the patient's treatment status was determined by the pattern of filled prescriptions. Thus, persistence could be measured in nonexperimental settings (for example, by using administrative databases).

            Studies addressing persistence included 2 randomized, controlled trials and 9 longitudinal cohort studies. These studies consistently showed that persistence with ARBs was somewhat better than persistence with ACE inhibitors (Table 3); for example, the median absolute difference in persistence rates for the longitudinal cohort studies was in the range of 6% to 7%.

            View this table:
            Table 3. Studies of Persistence*

            Certain caveats apply to these results. The longitudinal cohort studies typically used administrative databases. Although investigators in these studies often presented analyses that statistically controlled for differences in characteristics between patients receiving ACE inhibitors and those receiving ARBs, the absence of randomization means that similarity in unmeasured patient characteristics within the groups cannot be guaranteed. Consequently, the consistency of results reported in Table 3 (across experimental vs. nonexperimental studies, among the various longitudinal cohort studies, and over time within a study) is crucial. In addition, several longitudinal cohort studies, such as those by Marentette and colleagues (93), Bourgault and colleagues (88), Burke and colleagues (95), Wogen and colleagues (94), and Degli Esposti and colleagues (90, 91), corresponded in time to the introduction of ARBs and thus have relatively small sample sizes for this medication class. Persistence estimates are less precise in these studies than might be desired.

            Effects in Subgroups of Patients

            We found inadequate evidence regarding comparative effectiveness, adverse events, or tolerability of ACE inhibitors and ARBs for any particular patient subgroup (6).

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            Discussion

            With the exception of rates of cough, the available evidence does not strongly support the hypothesis that ACE inhibitors and ARBs have clinically meaningful differences in benefits or harms for individuals with essential hypertension. In particular, both classes of therapy provide similar levels of blood pressure control and seem to have an equivalent effect on death and cardiovascular events; major adverse events; quality of life; and risk factors, such as lipid levels, diabetes mellitus, and left ventricular mass and function. Evidence suggests that ARBs are associated with higher rates of persistence with initial therapy than are ACE inhibitors, although the magnitude of this difference is difficult to quantify.

            The literature had important limitations. Assessment of the long-term effect of treatment is restricted by the dearth of truly long-term studies; follow-up exceeded 6 months in only one third of head-to-head studies. Many of the studies reported limited data on patient characteristics, did not report results by subpopulation, and underrepresented black patients. Study protocols had substantial differences, including maximal medication dose, whether additional blood pressure medications were permitted, whether adjustments were by algorithm or physician discretion, and whether nonresponders were withdrawn at some point in the study.

            Assessment of outcomes was not uniform. Blood pressure was reported in some studies only as final blood pressure and in other studies as change in blood pressure. Important outcomes, such as death, vascular events, and angioedema, were often not mentioned.

            This review highlights several issues that should be addressed by further research. In addition to examining the effect of therapy over several years, studies should incorporate pragmatic designs, such as clinical trials in which treatment is consistent with typical clinical practice, or randomization by organizationally meaningful clusters, such as practice organizations or health plans. Assessments should consider subgroups of special importance, such as individuals with essential hypertension and diabetes mellitus, congestive heart failure, chronic kidney disease, and dyslipidemia, and should have broader representation of such groups as elderly persons and ethnic and racial minorities. Given the demonstrated higher incidence of cough with ACE inhibitors, it would also be valuable to gain a more precise understanding of the effect of cough on quality of life, care patterns (for example, use of therapeutic agents for cough symptoms or conditions associated with cough), and health outcomes, particularly for individuals who continue to use ACE inhibitors.

            Although a strong clinical motivation exists to differentiate among therapies to achieve optimal outcomes and to tailor treatment to the individual patient, this review indicates that, for the relatively low-risk individual with essential hypertension, any differences between ACE inhibitors and ARBs in major events or changes in risk factors are likely to be small. Identifying such small differences is a substantial challenge requiring large, prolonged studies in generalizable populations and settings. However, in the face of the considerable effect of marginal differences in treatment efficacy for common conditions, such an effort may well be justified.

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            Appendix 1: Methods for Reviewing Indirect Comparison StudiesGraphic

            Our review of the literature on the comparative long-term benefits and harms of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs) for treating hypertension focused, in the first instance, on direct head-to-head comparisons of drugs in the 2 classes. Because we were uncertain that these direct comparisons would adequately address all aspects of the key questions, we also sought to identify and screen potentially relevant indirect comparison studies—studies in which ACE inhibitors and ARBs were compared, in distinct trials, with a common comparator. This Appendix describes the methods we used to identify and review indirect comparison studies.

             
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            Search and Abstract Screening

            We began by searching MEDLINE for studies of ARBs versus other (non–ACE inhibitor) comparators, including placebo. We screened these abstracts along with the head-to-head trials. For indirect comparisons, we considered only randomized, controlled trials. We coded each included abstract for duration of treatment or follow-up (for example, “12 weeks” or “1 year”).

            Because a primary objective for evaluating non–head-to-head studies was to expand the pool of evidence regarding long-term results, we restricted the pool of abstracts for further evaluation to those with a duration of treatment or follow-up of at least 24 weeks. Further, because the credibility of any meta-analysis—particularly for non–head-to-head trials—depends on consistency among studies, we considered only comparators studied in at least 3 trials. The comparators thus identified were atenolol, amlodipine, and placebo.

            Next, we searched MEDLINE for studies of ACE inhibitors versus atenolol or amlodipine. To identify potentially relevant trials of ACE inhibitor versus placebo, we began by searching the references of the June 2005 Drug Class Review on ACE inhibitors (4) and supplemented this with a search of MEDLINE for articles published after that review. Finally, the abstracts for all ACE inhibitor versus other studies of treatments were screened for inclusion and evaluated further to identify trials with the right treatment duration or length of follow-up (≥24 weeks) and the right comparators (atenolol, amlodipine, or placebo).

            From this process, we identified 76 randomized, controlled trial publications comparing ARBs with atenolol, amlodipine, or placebo over at least 24 weeks, and 136 randomized, controlled trial publications comparing ACE inhibitors with the same group of comparators over the same period. We could not obtain 4 articles (2 each for ACE inhibitors and ARBs), so the final counts were 74 potentially relevant ARB articles and 134 potentially relevant ACE inhibitor articles.

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            Identifying Publications Reporting Outcomes of Interest

            Once data from the direct comparator trials had been abstracted, we identified 3 categories of outcomes that we thought were underreported in these trials: death and major events (myocardial infarction, stroke), measures of carbohydrate metabolism or diabetes control (progression to type 2 diabetes, hemoglobin A1c, insulin or other diabetes medication dosage, fasting plasma glucose, or aggregated measures of serial glucose measurements), and measures of kidney disease (creatinine level, glomerular filtration rate, and proteinuria). We then screened the indirect comparison literature identified through the process described above in full-text form to identify publications that reported on 1 or more of these outcomes. Thirty-two articles on ARBs versus other therapies and 42 articles on ACE inhibitors versus other therapies reported 1 or more of the outcomes of interest and were evaluated further.

            Previous Section
             

            Analysis of Comparability of Trials

            Because of the challenges of using indirect (non–head-to-head) comparison studies to infer relative efficacy regarding any particular health outcome, we established minimal criteria before considering any indirect comparison. Our goal was to achieve a reasonable degree of clinical homogeneity without being excessively restrictive at this stage.

            We defined 3 criteria for considering performing an indirect comparison. The first criterion was that the studies must have a common comparator (amlodipine, atenolol, or placebo), because comparators cannot be considered equivalent with regard to any particular health outcome. The second criterion was that study populations must be generally comparable, at least with regard to key characteristics relevant to the outcome being assessed. For studies examining event rates (mortality, stroke, or myocardial infarction), the key characteristic was the mean age of the population. For studies of laboratory measures (hemoglobin A1c, glucose, or creatinine level; glomerular filtration rate; or proteinuria), the key characteristic was the mean of the corresponding laboratory measure at baseline. The value for the key characteristic could be different by as much as 10% and still be considered comparable (for example, comparable studies for mortality rates in which the study with the highest mean age for patients was 70 years could have mean patient ages as low as 63 years). The third criterion was that among studies satisfying the preceding criteria, there must be more than 1 study of an ACE inhibitor versus the comparator and more than 1 study of an ARB versus the comparator. That is, indirect comparisons for a particular outcome were considered only if we could find at least 4 comparable studies to evaluate, 2 for an ACE inhibitor and 2 for an ARB. Notably, we did not restrict studies to the same ACE inhibitor or ARB, or any other protocol characteristics.

            Despite these relatively liberal criteria for considering indirect comparisons between ACE inhibitors and ARBs, we did not identify any appropriate candidate studies related to an outcome of special interest, and thus we did not attempt to use indirect evidence to infer relative effect of ACE inhibitors versus ARBs.

            Previous SectionNext Section

            Appendix 2: Applicability CriteriaGraphic

            We did not provide a global rating of applicability (such as “high” or “low”) because applicability may differ substantially depending on the user of the review. However, applicability of research studies was assessed by noting the most important potential limitations in a study's applicability from among the list described by Rothwell (24). These criteria, slightly adapted by the Scientific Resource Center, are reproduced below. Assessors were instructed to list the most important (up to 3) limitations affecting applicability, if any, on the basis of this list.

            Instructions to abstractors/assessors: Do not assign an overall applicability score. Instead, list the most important (up to 3) limitations affecting applicability, if any, based on the following list.

             
            Next Section

            Setting of the Study

            1. In which country (or countries) was the study conducted?

            2. In what health care system (or systems) was the study conducted?

            3. Were patients recruited from the primary, secondary, or tertiary care settings?

            4. How were study centers selected for participation?

            5. How were study clinicians selected for participation?

            Previous SectionNext Section

            Selection of Participants

            6. How were participants diagnosed and identified for eligibility screening before random allocation?

            7. What were the study eligibility criteria?

            8. What were the study exclusion criteria?

            9. Did the study require a run-in period with the control or placebo intervention?

            10. Did the study require a run-in period with the active intervention?

            11. Did the study selectively recruit participants who demonstrated a history of favorable or unfavorable response to drug or other interventions for the condition?

            12. Did the study report the ratio of randomly allocated participants to nonallocated participants (who were eligible)?

            13. Did the study report the proportion of eligible participants who declined random allocation?

            Previous SectionNext Section

            Characteristics of Study Participants

            14. Did the study report participants' baseline characteristics?

            15. Did the study report participants' race?

            16. Did the study report participants' underlying pathology?

            17. Did the study report participants' stage in the natural history of the disease?

            18. Did the study report participants' severity of disease?

            19. Did the study report participants' comorbid conditions?

            20. Did the study report participants' absolute risk of a poor outcome in the control arm?

            Previous SectionNext Section

            Differences between the Study Protocol and Routine Clinical Practice

            21. Were the study interventions (active arm) similar to interventions used in routine clinical practice?

            22. Was the timing of the intervention similar to the timing in routine clinical practice?

            23. Was the study's control arm appropriate and relevant in relation to routine clinical practice?

            24. Were the study's co-interventions—which were not randomly allocated—adequate to reflect routine clinical practice?

            25. Were any interventions prohibited by the study that are routinely used in clinical practice?

            26. Have there been diagnostic or therapeutic advances used in routine practice since the study was conducted?

            Previous SectionNext Section

            Outcome Measures and Follow-up

            27. If applicable, did the study use a clinically relevant surrogate outcome?

            28. If applicable, did the study use a scale that is clinically relevant, valid, and reproducible?

            29. If applicable, was the intervention beneficial on the most relevant components of the composite outcome?

            30. Which clinician measured the outcome (e.g., treating physician or surgeon)?

            31. Did the study use patient-centered outcomes?

            32. How frequently were participants followed in the study?

            33. Was the duration of participant follow-up adequate?

            Previous Section
             

            Adverse Effects of Treatment

            34. How completely did the study report the occurrence of relevant adverse effects?

            35. Did the study report the rates of treatment discontinuations?

            36. Were the study centers and/or clinicians selected on the basis of their skill or experience?

            37. Did the study exclude participants at elevated risk of intervention complications?

            38. Did the study exclude participants who suffered adverse effects during the run-in period?

            39. Did the study monitor participants intensively for early signs of adverse effects?

            Previous SectionNext Section

            Article and Author Information

            • Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be construed as endorsements by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

            • Grant Support: This project was funded under contract no. 290-02-0025 from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.

            • Potential Financial Conflicts of Interest: Honoraria: D.C. McCrory (AstraZeneca). Stock ownership or options (other than mutual funds): G.P. Samsa (Pfizer).

            • Requests for Single Reprints: David B. Matchar, MD, Duke Center for Clinical Health Policy Research, 2200 West Main Street, Suite 220, Durham, NC 27705; e-mail, david.matchar{at}duke.edu.

            • Current Author Addresses: Drs. Matchar, McCrory, Orlando, Patwardhan, Samsa, and Gray: Duke Center for Clinical Health Policy Research, 2200 West Main Street, Suite 220, Durham, NC 27705.

            • Dr. M.R. Patel: Duke Clinical Research Institute, North Pavilion, 2400 Pratt Street, Room 0311, Durham, NC 27705.

            • Dr. U.D. Patel: Department of Nephrology, Duke University Medical Center, DUMC Box 3646, Durham, NC 27710.

            • Dr. Powers: Duke University and Durham Veterans Affairs Medical Center, 2424 Erwin Road, Suite 1105, Durham, NC 27705.

            Previous Section
             

            References

            1. 1.↵
              World Health Organization. World health report 2002: reducing risks, promoting healthy life. Geneva: World Health Organization; 2002. Accessed at http://www.who.int/whr/2002 on 14 December 2006.
            2. 2.↵
              1. ChobanianAV,
              2. BakrisGL,
              3. BlackHR,
              4. CushmanWC,
              5. GreenLA,
              6. IzzoJL, Jr
              et al.National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood PressureThe Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.JAMA20032892560-72pmid:12748199
              Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al.; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-72. [PMID: 12748199]
              Abstract/FREE Full Text
            3. 3.↵
              1. IsrailiZH,
              2. HallWD
              Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology.Ann Intern Med1992117234-42pmid:1616218
              Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology. Ann Intern Med. 1992;117:234-42. [PMID: 1616218]
              Abstract/FREE Full Text
            4. 4.↵
              Chou R, Helfand M, Carson S. Drug Class Review on Angiotensin Converting Enzyme Inhibitors. Final Report. Portland, OR: Oregon Health & Science Univ; 2005. Accessed at http://www.ohsu.edu/drugeffectiveness/reports/final.cfm on 17 August 2006.
            5. 5.↵
              Furmaga E, Glassman P, Rhodes S, Suttorp M, Mojica W. Drug Class Review on Angiotensin II Receptor Antagonists. Final Report. Portland, OR: Oregon Health & Science Univ; 2006. Accessed at http://www.ohsu.edu/drugeffectiveness/reports/final.cfm on 17 August 2006.
            6. 6.↵
              Matchar DB, McCrory DC, Orlando LA, Patel MR, Patel UD, Patwardhan MB, et al. Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin II Receptor Antagonists (ARBs) for Treating Essential Hypertension. Comparative Effectiveness Review No. 10. (Prepared by Duke Evidence-based Practice Center under Contract No. 290-02-0025.) Rockville, MD: Agency for Healthcare Research and Quality; November 2007. Available at: http://www.effectivehealthcare.ahrq.gov/reports/final.cfm.
            7. 7.↵
              1. AnanF,
              2. TakahashiN,
              3. OoieT,
              4. YufuK,
              5. HaraM,
              6. NakagawaM
              et al.Effects of valsartan and perindopril combination therapy on left ventricular hypertrophy and aortic arterial stiffness in patients with essential hypertension.Eur J Clin Pharmacol200561353-9pmid:15918057
              Anan F, Takahashi N, Ooie T, Yufu K, Hara M, Nakagawa M, et al. Effects of valsartan and perindopril combination therapy on left ventricular hypertrophy and aortic arterial stiffness in patients with essential hypertension. Eur J Clin Pharmacol. 2005;61:353-9. [PMID: 15918057]
              CrossRefMedlineWeb of Science
            8. 8.↵
              1. AndersenNH,
              2. PoulsenSH,
              3. PoulsenPL,
              4. KnudsenST,
              5. HellebergK,
              6. HansenKW
              et al.Effects of blood pressure lowering and metabolic control on systolic left ventricular function in type II diabetes mellitus.Clin Sci (Lond)200611153-9pmid:16512787
              Andersen NH, Poulsen SH, Poulsen PL, Knudsen ST, Helleberg K, Hansen KW, et al. Effects of blood pressure lowering and metabolic control on systolic left ventricular function in type II diabetes mellitus. Clin Sci (Lond). 2006;111:53-9. [PMID: 16512787]
              Medline
            9. 9.↵
              1. FogariR,
              2. MugelliniA,
              3. ZoppiA,
              4. LazzariP,
              5. DestroM,
              6. RinaldiA
              et al.Effect of telmisartan/hydrochlorothiazide vs lisinopril/hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients.J Hum Hypertens200620177-85pmid:16306998
              Fogari R, Mugellini A, Zoppi A, Lazzari P, Destro M, Rinaldi A, et al. Effect of telmisartan/hydrochlorothiazide vs lisinopril/hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients. J Hum Hypertens. 2006;20:177-85. [PMID: 16306998]
              CrossRefMedlineWeb of Science
            10. 10.↵
              1. HosohataK,
              2. SaitoS,
              3. AsayamaK,
              4. OhkuboT,
              5. KikuyaM,
              6. MetokiH
              et al.Progress report on The Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study: status at February 2004.Clin Exp Hypertens20072969-81pmid:17190733
              Hosohata K, Saito S, Asayama K, Ohkubo T, Kikuya M, Metoki H, et al. Progress report on The Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study: status at February 2004. Clin Exp Hypertens. 2007;29:69-81. [PMID: 17190733]
              CrossRefMedline
            11. 11.↵
              1. KyvelouSM,
              2. VyssoulisGP,
              3. KarpanouEA,
              4. AdamopoulosDN,
              5. ZervoudakiAI,
              6. PietriPG
              et al.Effects of antihypertensive treatment with angiotensin II receptor blockers on lipid profile: an open multi-drug comparison trial.Hellenic J Cardiol20064721-8pmid:16532712
              Kyvelou SM, Vyssoulis GP, Karpanou EA, Adamopoulos DN, Zervoudaki AI, Pietri PG, et al. Effects of antihypertensive treatment with angiotensin II receptor blockers on lipid profile: an open multi-drug comparison trial. Hellenic J Cardiol. 2006;47:21-8. [PMID: 16532712]
              Medline
            12. 12.↵
              1. MochizukiS,
              2. DahlofB,
              3. ShimizuM,
              4. IkewakiK,
              5. YoshikawaM,
              6. TaniguchiI
              et al.Jikei Heart Study GroupValsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study.Lancet20073691431-9pmid:17467513
              Mochizuki S, Dahlof B, Shimizu M, Ikewaki K, Yoshikawa M, Taniguchi I, et al.; Jikei Heart Study Group. Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study. Lancet. 2007;369:1431-9. [PMID: 17467513]
              CrossRefMedlineWeb of Science
            13. 13.↵
              1. OgawaS,
              2. TakeuchiK,
              3. MoriT,
              4. NakoK,
              5. TsubonoY,
              6. ItoS
              Effects of monotherapy of temocapril or candesartan with dose increments or combination therapy with both drugs on the suppression of diabetic nephropathy.Hypertens Res200730325-34pmid:17541211
              Ogawa S, Takeuchi K, Mori T, Nako K, Tsubono Y, Ito S. Effects of monotherapy of temocapril or candesartan with dose increments or combination therapy with both drugs on the suppression of diabetic nephropathy. Hypertens Res. 2007;30:325-34. [PMID: 17541211]
              CrossRefMedlineWeb of Science
            14. 14.↵
              1. Palma-GámizJL,
              2. PêgoM,
              3. ContrerasEM,
              4. AngladaMP,
              5. MartínezJO,
              6. EsquerraEA
              et al.Iberian Multicenter Imidapril Study on HypertensionA twelve-week, multicenter, randomized, double-blind, parallel-group, noninferiority trial of the antihypertensive efficacy and tolerability of imidapril and candesartan in adult patients with mild to moderate essential hypertension: the Iberian Multicenter Imidapril Study on Hypertension (IMISH).Clin Ther2006282040-51pmid:17296460
              Palma-Gámiz JL, Pêgo M, Contreras EM, Anglada MP, Martínez JO, Esquerra EA, et al.; Iberian Multicenter Imidapril Study on Hypertension. A twelve-week, multicenter, randomized, double-blind, parallel-group, noninferiority trial of the antihypertensive efficacy and tolerability of imidapril and candesartan in adult patients with mild to moderate essential hypertension: the Iberian Multicenter Imidapril Study on Hypertension (IMISH). Clin Ther. 2006;28:2040-51. [PMID: 17296460]
              CrossRefMedline
            15. 15.↵
              1. Palma-GamizJL,
              2. PêgoM,
              3. MarquezE,
              4. PujolM,
              5. OlivanJ,
              6. AlegríaE
              et al.A multicentre, 12-week study of imidapril and candesartan cilexetil in patients with mild to moderate hypertension using ambulatory blood pressure monitoring.Clin Drug Investig200727407-17pmid:17506591
              Palma-Gamiz JL, Pêgo M, Marquez E, Pujol M, Olivan J, Alegría E, et al. A multicentre, 12-week study of imidapril and candesartan cilexetil in patients with mild to moderate hypertension using ambulatory blood pressure monitoring. Clin Drug Investig. 2007;27:407-17. [PMID: 17506591]
              Medline
            16. 16.↵
              1. PalmasW,
              2. MaS,
              3. PsatyB,
              4. GoffDC, Jr,
              5. DarwinC,
              6. BarrRG
              Antihypertensive medications and C-reactive protein in the multi-ethnic study of atherosclerosis.Am J Hypertens200720233-41pmid:17324732
              Palmas W, Ma S, Psaty B, Goff DC Jr, Darwin C, Barr RG. Antihypertensive medications and C-reactive protein in the multi-ethnic study of atherosclerosis. Am J Hypertens. 2007;20:233-41. [PMID: 17324732]
              CrossRefMedlineWeb of Science
            17. 17.↵
              1. RehmanA,
              2. IsmailSB,
              3. NaingL,
              4. RoshanTM,
              5. RahmanAR
              Reduction in arterial stiffness with angiotensin II antagonism and converting enzyme inhibition. A comparative study among Malay hypertensive subjects with a known genetic profile.Am J Hypertens200720184-9pmid:17261465
              Rehman A, Ismail SB, Naing L, Roshan TM, Rahman AR. Reduction in arterial stiffness with angiotensin II antagonism and converting enzyme inhibition. A comparative study among Malay hypertensive subjects with a known genetic profile. Am J Hypertens. 2007;20:184-9. [PMID: 17261465]
              Medline
            18. 18.↵
              1. ScaglioneR,
              2. ArganoC,
              3. Di ChiaraT,
              4. ParrinelloG,
              5. ColombaD,
              6. AvelloneG
              et al.Effect of dual blockade of renin-angiotensin system on TGFbeta1 and left ventricular structure and function in hypertensive patients.J Hum Hypertens200721307-15pmid:17301824
              Scaglione R, Argano C, Di Chiara T, Parrinello G, Colomba D, Avellone G, et al. Effect of dual blockade of renin-angiotensin system on TGFbeta1 and left ventricular structure and function in hypertensive patients. J Hum Hypertens. 2007;21:307-15. [PMID: 17301824]
              MedlineWeb of Science
            19. 19.↵
              1. SengulAM,
              2. AltuntasY,
              3. KürklüA,
              4. AydinL
              Beneficial effect of lisinopril plus telmisartan in patients with type 2 diabetes, microalbuminuria and hypertension.Diabetes Res Clin Pract200671210-9pmid:16112244
              Sengul AM, Altuntas Y, Kürklü A, Aydin L. Beneficial effect of lisinopril plus telmisartan in patients with type 2 diabetes, microalbuminuria and hypertension. Diabetes Res Clin Pract. 2006;71:210-9. [PMID: 16112244]
              CrossRefMedlineWeb of Science
            20. 20.↵
              1. Spoelstra-de ManAM,
              2. van IttersumFJ,
              3. SchramMT,
              4. KampO,
              5. van DijkRA,
              6. IjzermanRG
              et al.Aggressive antihypertensive strategies based on hydrochlorothiazide, candesartan or lisinopril decrease left ventricular mass and improve arterial compliance in patients with type II diabetes mellitus and hypertension.J Hum Hypertens200620599-611pmid:16673014
              Spoelstra-de Man AM, van Ittersum FJ, Schram MT, Kamp O, van Dijk RA, Ijzerman RG, et al. Aggressive antihypertensive strategies based on hydrochlorothiazide, candesartan or lisinopril decrease left ventricular mass and improve arterial compliance in patients with type II diabetes mellitus and hypertension. J Hum Hypertens. 2006;20:599-611. [PMID: 16673014]
              Medline
            21. 21.↵
              1. TedescoMA,
              2. NataleF,
              3. CalabròR
              Effects of monotherapy and combination therapy on blood pressure control and target organ damage: a randomized prospective intervention study in a large population of hypertensive patients.J Clin Hypertens (Greenwich)20068634-41pmid:16957425
              Tedesco MA, Natale F, Calabrò R. Effects of monotherapy and combination therapy on blood pressure control and target organ damage: a randomized prospective intervention study in a large population of hypertensive patients. J Clin Hypertens (Greenwich). 2006;8:634-41. [PMID: 16957425]
              Medline
            22. 22.↵
              1. HarrisRP,
              2. HelfandM,
              3. WoolfSH,
              4. LohrKN,
              5. MulrowCD,
              6. TeutschSM
              et al.Methods Work GroupThird US Preventive Services Task ForceCurrent methods of the US Preventive Services Task Force: a review of the process.Am J Prev Med20012021-35pmid:11306229
              Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, et al.; Methods Work Group, Third US Preventive Services Task Force. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med. 2001;20:21-35. [PMID: 11306229]
              Medline
            23. 23.↵
              Undertaking systematic reviews of research on effectiveness: CRD's guidance for those carrying out or commissioning reviews. CRD report no. 4. 2nd ed.York, United KingdomNHS Centre for Reviews and Dissemination2001
              Undertaking systematic reviews of research on effectiveness: CRD's guidance for those carrying out or commissioning reviews. CRD report no. 4. 2nd ed. York, United Kingdom: NHS Centre for Reviews and Dissemination; 2001.
            24. 24.↵
              1. RothwellPM
              External validity of randomised controlled trials: “to whom do the results of this trial apply?”.Lancet200536582-93pmid:15639683
              Rothwell PM. External validity of randomised controlled trials: “to whom do the results of this trial apply?”. Lancet. 2005;365:82-93. [PMID: 15639683]
              CrossRefMedlineWeb of Science
            25. 25.↵
              1. AtkinsD,
              2. BestD,
              3. BrissPA,
              4. EcclesM,
              5. Falck-YtterY,
              6. FlottorpS
              et al.GRADE Working GroupGrading quality of evidence and strength of recommendations.BMJ20043281490pmid:15205295
              Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, et al.; GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ. 2004;328:1490. [PMID: 15205295]
              Abstract/FREE Full Text
            26. 26.↵
              1. BradburnMJ,
              2. DeeksJJ,
              3. BerlinJA,
              4. LocalioAR
              Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events.Stat Med20072653-77pmid:16596572
              Bradburn MJ, Deeks JJ, Berlin JA, Localio AR. Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med. 2007;26:53-77. [PMID: 16596572]
              CrossRefMedlineWeb of Science
            27. 27.↵
              1. ArgenzianoL,
              2. TrimarcoB
              Effect of eprosartan and enalapril in the treatment of elderly hypertensive patients: subgroup analysis of a 26-week, double-blind, multicentre study. Eprosartan Multinational Study Group.Curr Med Res Opin1999159-14pmid:10216806
              Argenziano L, Trimarco B. Effect of eprosartan and enalapril in the treatment of elderly hypertensive patients: subgroup analysis of a 26-week, double-blind, multicentre study. Eprosartan Multinational Study Group. Curr Med Res Opin. 1999;15:9-14. [PMID: 10216806]
              Medline
            28. 28.↵
              1. AvanzaAC, Jr,
              2. El AouarLM,
              3. MillJG
              Reduction in left ventricular hypertrophy in hypertensive patients treated with enalapril, losartan or the combination of enalapril and losartan.Arq Bras Cardiol200074103-17pmid:10904284
              Avanza AC Jr, El Aouar LM, Mill JG. Reduction in left ventricular hypertrophy in hypertensive patients treated with enalapril, losartan or the combination of enalapril and losartan. Arq Bras Cardiol. 2000;74:103-17. [PMID: 10904284]
              Medline
            29. 29.↵
              1. BarnettAH,
              2. BainSC,
              3. BouterP,
              4. KarlbergB,
              5. MadsbadS,
              6. JervellJ
              et al.Diabetics Exposed to Telmisartan and Enalapril Study GroupAngiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy.N Engl J Med20043511952-61pmid:15516696
              Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J, et al.; Diabetics Exposed to Telmisartan and Enalapril Study Group. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med. 2004;351:1952-61. [PMID: 15516696]
              Abstract/FREE Full Text
            30. 30.↵
              1. BlackHR,
              2. GraffA,
              3. ShuteD,
              4. StoltzR,
              5. RuffD,
              6. LevineJ
              et al.Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy, tolerability and safety compared to an angiotensin-converting enzyme inhibitor, lisinopril.J Hum Hypertens199711483-9pmid:9322828
              Black HR, Graff A, Shute D, Stoltz R, Ruff D, Levine J, et al. Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy, tolerability and safety compared to an angiotensin-converting enzyme inhibitor, lisinopril. J Hum Hypertens. 1997;11:483-9. [PMID: 9322828]
              CrossRefMedlineWeb of Science
            31. 31.↵
              1. BreezeE,
              2. RakeEC,
              3. DonoghueMD,
              4. FletcherAE
              Comparison of quality of life and cough on eprosartan and enalapril in people with moderate hypertension.J Hum Hypertens200115857-62pmid:11773988
              Breeze E, Rake EC, Donoghue MD, Fletcher AE. Comparison of quality of life and cough on eprosartan and enalapril in people with moderate hypertension. J Hum Hypertens. 2001;15:857-62. [PMID: 11773988]
              Medline
            32. 32.↵
              1. CelikT,
              2. IyisoyA,
              3. KursakliogluH,
              4. YilmazMI,
              5. KoseS,
              6. KilicS
              et al.The comparative effects of telmisartan and ramipril on P-wave dispersion in hypertensive patients: a randomized clinical study.Clin Cardiol200528298-302pmid:16028466
              Celik T, Iyisoy A, Kursaklioglu H, Yilmaz MI, Kose S, Kilic S, et al. The comparative effects of telmisartan and ramipril on P-wave dispersion in hypertensive patients: a randomized clinical study. Clin Cardiol. 2005;28:298-302. [PMID: 16028466]
              CrossRefMedlineWeb of Science
            33. 33.↵
              1. CocaA,
              2. CalvoC,
              3. Garcia-PuigJ,
              4. Gil-ExtremeraB,
              5. AguileraMT,
              6. de la SierraA
              et al.MAPAVEL Investigators (Monitorizacíon Ambulatoria Presión Arterial APROVEL)A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: the MAPAVEL Study (Monitorización Ambulatoria Presión Arterial APROVEL).Clin Ther200224126-38pmid:11833827
              Coca A, Calvo C, Garcia-Puig J, Gil-Extremera B, Aguilera MT, de la Sierra A, et al.; MAPAVEL Investigators (Monitorizacíon Ambulatoria Presión Arterial APROVEL). A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: the MAPAVEL Study (Monitorización Ambulatoria Presión Arterial APROVEL). Clin Ther. 2002;24:126-38. [PMID: 11833827]
              CrossRefMedline
            34. 34.↵
              1. CuspidiC,
              2. MuiesanML,
              3. ValagussaL,
              4. SalvettiM,
              5. Di BiagioC,
              6. Agabiti-RoseiE
              et al.CATCH investigatorsComparative effects of candesartan and enalapril on left ventricular hypertrophy in patients with essential hypertension: the candesartan assessment in the treatment of cardiac hypertrophy (CATCH) study.J Hypertens2002202293-300pmid:12409969
              Cuspidi C, Muiesan ML, Valagussa L, Salvetti M, Di Biagio C, Agabiti-Rosei E, et al.; CATCH investigators. Comparative effects of candesartan and enalapril on left ventricular hypertrophy in patients with essential hypertension: the candesartan assessment in the treatment of cardiac hypertrophy (CATCH) study. J Hypertens. 2002;20:2293-300. [PMID: 12409969]
              CrossRefMedlineWeb of Science
            35. 35.↵
              1. De RosaML,
              2. CardaceP,
              3. RossiM,
              4. BaianoA,
              5. de CristofaroA
              Comparative effects of chronic ACE inhibition and AT1 receptor blocked losartan on cardiac hypertrophy and renal function in hypertensive patients.J Hum Hypertens200216133-40pmid:11850771
              De Rosa ML, Cardace P, Rossi M, Baiano A, de Cristofaro A. Comparative effects of chronic ACE inhibition and AT1 receptor blocked losartan on cardiac hypertrophy and renal function in hypertensive patients. J Hum Hypertens. 2002;16:133-40. [PMID: 11850771]
              CrossRefMedline
            36. 36.↵
              1. DerosaG,
              2. CiceroAF,
              3. CiccarelliL,
              4. FogariR
              A randomized, double-blind, controlled, parallel-group comparison of perindopril and candesartan in hypertensive patients with type 2 diabetes mellitus.Clin Ther2003252006-21pmid:12946547
              Derosa G, Cicero AF, Ciccarelli L, Fogari R. A randomized, double-blind, controlled, parallel-group comparison of perindopril and candesartan in hypertensive patients with type 2 diabetes mellitus. Clin Ther. 2003;25:2006-21. [PMID: 12946547]
              CrossRefMedlineWeb of Science
            37. 37.↵
              1. EguchiK,
              2. KarioK,
              3. ShimadaK
              Comparison of candesartan with lisinopril on ambulatory blood pressure and morning surge in patients with systemic hypertension.Am J Cardiol200392621-4pmid:12943892
              Eguchi K, Kario K, Shimada K. Comparison of candesartan with lisinopril on ambulatory blood pressure and morning surge in patients with systemic hypertension. Am J Cardiol. 2003;92:621-4. [PMID: 12943892]
              CrossRefMedline
            38. 38.↵
              1. ElliottWJ
              Double-blind comparison of eprosartan and enalapril on cough and blood pressure in unselected hypertensive patients. Eprosartan Study Group.J Hum Hypertens199913413-7pmid:10408592
              Elliott WJ. Double-blind comparison of eprosartan and enalapril on cough and blood pressure in unselected hypertensive patients. Eprosartan Study Group. J Hum Hypertens. 1999;13:413-7. [PMID: 10408592]
              CrossRefMedlineWeb of Science
            39. 39.↵
              1. FogariR,
              2. MugelliniA,
              3. ZoppiA,
              4. CorradiL,
              5. PretiP,
              6. LazzariP
              et al.Losartan and perindopril effects on plasma plasminogen activator inhibitor-1 and fibrinogen in hypertensive type 2 diabetic patients.Am J Hypertens200215316-20pmid:11991216
              Fogari R, Mugellini A, Zoppi A, Corradi L, Preti P, Lazzari P, et al. Losartan and perindopril effects on plasma plasminogen activator inhibitor-1 and fibrinogen in hypertensive type 2 diabetic patients. Am J Hypertens. 2002;15:316-20. [PMID: 11991216]
              CrossRefMedlineWeb of Science
            40. 40.↵
              1. FogariR,
              2. ZoppiA,
              3. PretiP,
              4. FogariE,
              5. MalamaniG,
              6. MugelliniA
              Differential effects of ACE-inhibition and angiotensin II antagonism on fibrinolysis and insulin sensitivity in hypertensive postmenopausal women.Am J Hypertens200114921-6pmid:11587159
              Fogari R, Zoppi A, Preti P, Fogari E, Malamani G, Mugellini A. Differential effects of ACE-inhibition and angiotensin II antagonism on fibrinolysis and insulin sensitivity in hypertensive postmenopausal women. Am J Hypertens. 2001;14:921-6. [PMID: 11587159]
              CrossRefMedlineWeb of Science
            41. 41.↵
              1. GavrasI,
              2. GavrasH
              Effects of eprosartan versus enalapril in hypertensive patients on the renin-angiotensin-aldosterone system and safety parameters: results from a 26-week, double-blind, multicentre study. Eprosartan Multinational Study Group.Curr Med Res Opin19991515-24pmid:10216807
              Gavras I, Gavras H. Effects of eprosartan versus enalapril in hypertensive patients on the renin-angiotensin-aldosterone system and safety parameters: results from a 26-week, double-blind, multicentre study. Eprosartan Multinational Study Group. Curr Med Res Opin. 1999;15:15-24. [PMID: 10216807]
              Medline
            42. 42.↵
              1. GhiadoniL,
              2. MagagnaA,
              3. VersariD,
              4. KardaszI,
              5. HuangY,
              6. TaddeiS
              et al.Different effect of antihypertensive drugs on conduit artery endothelial function.Hypertension2003411281-6pmid:12719441
              Ghiadoni L, Magagna A, Versari D, Kardasz I, Huang Y, Taddei S, et al. Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension. 2003;41:1281-6. [PMID: 12719441]
              Abstract/FREE Full Text
            43. 43.↵
              1. KarlbergBE,
              2. LinsLE,
              3. HermanssonK
              Efficacy and safety of telmisartan, a selective AT1 receptor antagonist, compared with enalapril in elderly patients with primary hypertension. TEES Study Group.J Hypertens199917293-302pmid:10067800
              Karlberg BE, Lins LE, Hermansson K. Efficacy and safety of telmisartan, a selective AT1 receptor antagonist, compared with enalapril in elderly patients with primary hypertension. TEES Study Group. J Hypertens. 1999;17:293-302. [PMID: 10067800]
              MedlineWeb of Science
            44. 44.↵
              1. KavgaciH,
              2. SahinA,
              3. Onder ErsozH,
              4. EremC,
              5. OzdemirF
              The effects of losartan and fosinopril in hypertensive type 2 diabetic patients.Diabetes Res Clin Pract20025819-25pmid:12161053
              Kavgaci H, Sahin A, Onder Ersoz H, Erem C, Ozdemir F. The effects of losartan and fosinopril in hypertensive type 2 diabetic patients. Diabetes Res Clin Pract. 2002;58:19-25. [PMID: 12161053]
              Medline
            45. 45.↵
              1. KoylanN,
              2. AcarturkE,
              3. CanberkA,
              4. CaglarN,
              5. CaglarS,
              6. ErdineS
              et al.Turkish Irbesartan Study GroupEffect of irbesartan monotherapy compared with ACE inhibitors and calcium-channel blockers on patient compliance in essential hypertension patients: a multicenter, open-labeled, three-armed study.Blood Press Suppl2005123-31pmid:16060413
              Koylan N, Acarturk E, Canberk A, Caglar N, Caglar S, Erdine S, et al.; Turkish Irbesartan Study Group. Effect of irbesartan monotherapy compared with ACE inhibitors and calcium-channel blockers on patient compliance in essential hypertension patients: a multicenter, open-labeled, three-armed study. Blood Press Suppl. 2005;1:23-31. [PMID: 16060413]
              Medline
            46. 46.↵
              1. LacourcièreY,
              2. BélangerA,
              3. GodinC,
              4. HalléJP,
              5. RossS,
              6. WrightN
              et al.Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy.Kidney Int200058762-9pmid:10916100
              Lacourcière Y, Bélanger A, Godin C, Hallé JP, Ross S, Wright N, et al. Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy. Kidney Int. 2000;58:762-9. [PMID: 10916100]
              CrossRefMedlineWeb of Science
            47. 47.↵
              1. LarochelleP,
              2. FlackJM,
              3. MarburyTC,
              4. SareliP,
              5. KriegerEM,
              6. ReevesRA
              Effects and tolerability of irbesartan versus enalapril in patients with severe hypertension. Irbesartan Multicenter Investigators.Am J Cardiol1997801613-5pmid:9416950
              Larochelle P, Flack JM, Marbury TC, Sareli P, Krieger EM, Reeves RA. Effects and tolerability of irbesartan versus enalapril in patients with severe hypertension. Irbesartan Multicenter Investigators. Am J Cardiol. 1997;80:1613-5. [PMID: 9416950]
              CrossRefMedlineWeb of Science
            48. 48.↵
              1. LevineB
              Effect of eprosartan and enalapril in the treatment of black hypertensive patients: subgroup analysis of a 26-week, double-blind, multicentre study. Eprosartan Multinational Study Group.Curr Med Res Opin19991525-32pmid:10216808
              Levine B. Effect of eprosartan and enalapril in the treatment of black hypertensive patients: subgroup analysis of a 26-week, double-blind, multicentre study. Eprosartan Multinational Study Group. Curr Med Res Opin. 1999;15:25-32. [PMID: 10216808]
              Medline
            49. 49.↵
              1. MalaccoE,
              2. SantonastasoM,
              3. VariNA,
              4. GargiuloA,
              5. SpagnuoloV,
              6. BertocchiF
              et al.Blood Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril StudyComparison of valsartan 160 mg with lisinopril 20 mg, given as monotherapy or in combination with a diuretic, for the treatment of hypertension: the Blood Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril (PREVAIL) study.Clin Ther200426855-65pmid:15262456
              Malacco E, Santonastaso M, Vari NA, Gargiulo A, Spagnuolo V, Bertocchi F, et al.; Blood Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril Study. Comparison of valsartan 160 mg with lisinopril 20 mg, given as monotherapy or in combination with a diuretic, for the treatment of hypertension: the Blood Pressure Reduction and Tolerability of Valsartan in Comparison with Lisinopril (PREVAIL) study. Clin Ther. 2004;26:855-65. [PMID: 15262456]
              Medline
            50. 50.↵
              1. MatsudaH,
              2. HayashiK,
              3. SarutaT
              Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease.J Hum Hypertens200317271-6pmid:12692572
              Matsuda H, Hayashi K, Saruta T. Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease. J Hum Hypertens. 2003;17:271-6. [PMID: 12692572]
              Medline
            51. 51.↵
              1. McInnesGT,
              2. O'KaneKP,
              3. IstadH,
              4. Keinänen-KiukaanniemiS,
              5. Van MierloHF
              Comparison of the AT1-receptor blocker, candesartan cilexetil, and the ACE inhibitor, lisinopril, in fixed combination with low dose hydrochlorothiazide in hypertensive patients.J Hum Hypertens200014263-9pmid:10805052
              McInnes GT, O'Kane KP, Istad H, Keinänen-Kiukaanniemi S, Van Mierlo HF. Comparison of the AT1-receptor blocker, candesartan cilexetil, and the ACE inhibitor, lisinopril, in fixed combination with low dose hydrochlorothiazide in hypertensive patients. J Hum Hypertens. 2000;14:263-9. [PMID: 10805052]
              CrossRefMedlineWeb of Science
            52. 52.↵
              1. MimranA,
              2. RuilopeL,
              3. KerwinL,
              4. NysM,
              5. OwensD,
              6. Kassler-TaubK
              et al.A randomised, double-blind comparison of the angiotensin II receptor antagonist, irbesartan, with the full dose range of enalapril for the treatment of mild-to-moderate hypertension.J Hum Hypertens199812203-8pmid:9579771
              Mimran A, Ruilope L, Kerwin L, Nys M, Owens D, Kassler-Taub K, et al. A randomised, double-blind comparison of the angiotensin II receptor antagonist, irbesartan, with the full dose range of enalapril for the treatment of mild-to-moderate hypertension. J Hum Hypertens. 1998;12:203-8. [PMID: 9579771]
              CrossRefMedlineWeb of Science
            53. 53.↵
              1. MogensenCE,
              2. NeldamS,
              3. TikkanenI,
              4. OrenS,
              5. ViskoperR,
              6. WattsRW
              et al.Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study.BMJ20003211440-4pmid:11110735
              Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW, et al. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ. 2000;321:1440-4. [PMID: 11110735]
              Abstract/FREE Full Text
            54. 54.↵
              1. NaidooDP,
              2. SareliP,
              3. MarinF,
              4. Aroca-MartinezG,
              5. MaritzFJ,
              6. JardimPC
              et al.Increased efficacy and tolerability with losartan plus hydrochlorothiazide in patients with uncontrolled hypertension and therapy-related symptoms receiving two monotherapies.Adv Ther199916187-99pmid:10915394
              Naidoo DP, Sareli P, Marin F, Aroca-Martinez G, Maritz FJ, Jardim PC, et al. Increased efficacy and tolerability with losartan plus hydrochlorothiazide in patients with uncontrolled hypertension and therapy-related symptoms receiving two monotherapies. Adv Ther. 1999;16:187-99. [PMID: 10915394]
              MedlineWeb of Science
            55. 55.↵
              1. NeutelJM,
              2. FrishmanWH,
              3. OparilS,
              4. PapademitriouV,
              5. GuthrieG
              Comparison of telmisartan with lisinopril in patients with mild-to-moderate hypertension.Am J Ther19996161-6pmid:10423659
              Neutel JM, Frishman WH, Oparil S, Papademitriou V, Guthrie G. Comparison of telmisartan with lisinopril in patients with mild-to-moderate hypertension. Am J Ther. 1999;6:161-6. [PMID: 10423659]
              Medline
            56. 56.↵
              1. RabbiaF,
              2. SilkeB,
              3. CarraR,
              4. MilanA,
              5. Del ColleS,
              6. PugniC
              et al.Heart rate variability and baroreflex sensitivity during fosinopril, irbesartan and atenolol therapy in hypertension.Clin Drug Investig200424651-9pmid:17523728
              Rabbia F, Silke B, Carra R, Milan A, Del Colle S, Pugni C, et al. Heart rate variability and baroreflex sensitivity during fosinopril, irbesartan and atenolol therapy in hypertension. Clin Drug Investig. 2004;24:651-9. [PMID: 17523728]
              Medline
            57. 57.↵
              1. RajzerM,
              2. KlocekM,
              3. Kawecka-JaszczK
              Effect of amlodipine, quinapril, and losartan on pulse wave velocity and plasma collagen markers in patients with mild-to-moderate arterial hypertension.Am J Hypertens200316439-44pmid:12799091
              Rajzer M, Klocek M, Kawecka-Jaszcz K. Effect of amlodipine, quinapril, and losartan on pulse wave velocity and plasma collagen markers in patients with mild-to-moderate arterial hypertension. Am J Hypertens. 2003;16:439-44. [PMID: 12799091]
              CrossRefMedlineWeb of Science
            58. 58.↵
              1. RoseiEA,
              2. RizzoniD,
              3. MuiesanML,
              4. SleimanI,
              5. SalvettiM,
              6. MonteduroC
              et al.CENTRO (CandEsartaN on aTherosclerotic Risk factors) Study InvestigatorsEffects of candesartan cilexetil and enalapril on inflammatory markers of atherosclerosis in hypertensive patients with non-insulin-dependent diabetes mellitus.J Hypertens200523435-44pmid:15662233
              Rosei EA, Rizzoni D, Muiesan ML, Sleiman I, Salvetti M, Monteduro C, et al.; CENTRO (CandEsartaN on aTherosclerotic Risk factors) Study Investigators. Effects of candesartan cilexetil and enalapril on inflammatory markers of atherosclerosis in hypertensive patients with non-insulin-dependent diabetes mellitus. J Hypertens. 2005;23:435-44. [PMID: 15662233]
              CrossRefMedlineWeb of Science
            59. 59.↵
              1. RuilopeL,
              2. JägerB,
              3. PrichardB
              Eprosartan versus enalapril in elderly patients with hypertension: a double-blind, randomized trial.Blood Press200110223-9pmid:11800061
              Ruilope L, Jäger B, Prichard B. Eprosartan versus enalapril in elderly patients with hypertension: a double-blind, randomized trial. Blood Press. 2001;10:223-9. [PMID: 11800061]
              CrossRefMedlineWeb of Science
            60. 60.↵
              1. SaitoS,
              2. AsayamaK,
              3. OhkuboT,
              4. KikuyaM,
              5. MetokiH,
              6. ObaraT
              et al.HOMED-BP Study GroupThe second progress report on the Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study.Blood Press Monit20049243-7pmid:15472496
              Saito S, Asayama K, Ohkubo T, Kikuya M, Metoki H, Obara T, et al.; HOMED-BP Study Group. The second progress report on the Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study. Blood Press Monit. 2004;9:243-7. [PMID: 15472496]
              Medline
            61. 61.↵
              1. SchiefferB,
              2. BünteC,
              3. WitteJ,
              4. HoeperK,
              5. BögerRH,
              6. SchwedhelmE
              et al.Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease.J Am Coll Cardiol200444362-8pmid:15261932
              Schieffer B, Bünte C, Witte J, Hoeper K, Böger RH, Schwedhelm E, et al. Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease. J Am Coll Cardiol. 2004;44:362-8. [PMID: 15261932]
              Abstract/FREE Full Text
            62. 62.↵
              1. SchramMT,
              2. van IttersumFJ,
              3. Spoelstra-de ManA,
              4. van DijkRA,
              5. SchalkwijkCG,
              6. IjzermanRG
              et al.Aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril as initial choice in hypertensive type II diabetic individuals: effects on albumin excretion, endothelial function and inflammation in a double-blind, randomized clinical trial.J Hum Hypertens200519429-37pmid:15647778
              Schram MT, van Ittersum FJ, Spoelstra-de Man A, van Dijk RA, Schalkwijk CG, Ijzerman RG, et al. Aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril as initial choice in hypertensive type II diabetic individuals: effects on albumin excretion, endothelial function and inflammation in a double-blind, randomized clinical trial. J Hum Hypertens. 2005;19:429-37. [PMID: 15647778]
              CrossRefMedline
            63. 63.↵
              1. ShandBI
              Haemorheological effects of losartan and enalapril in patients with renal parenchymal disease and hypertension.J Hum Hypertens200014305-9pmid:10822316
              Shand BI. Haemorheological effects of losartan and enalapril in patients with renal parenchymal disease and hypertension. J Hum Hypertens. 2000;14:305-9. [PMID: 10822316]
              Medline
            64. 64.↵
              1. ShandBI,
              2. LynnKL
              A comparative study of losartan and enalapril on erythropoiesis and renal function in hypertensive patients with renal parenchymal disease [Letter].Clin Nephrol200054427-8pmid:11105808
              Shand BI, Lynn KL. A comparative study of losartan and enalapril on erythropoiesis and renal function in hypertensive patients with renal parenchymal disease [Letter]. Clin Nephrol. 2000;54:427-8. [PMID: 11105808]
              MedlineWeb of Science
            65. 65.↵
              1. ShibasakiY,
              2. MasakiH,
              3. NishiueT,
              4. NishikawaM,
              5. MatsubaraH,
              6. IwasakaT
              Angiotensin II type 1 receptor antagonist, losartan, causes regression of left ventricular hypertrophy in end-stage renal disease.Nephron200290256-61pmid:11867945
              Shibasaki Y, Masaki H, Nishiue T, Nishikawa M, Matsubara H, Iwasaka T. Angiotensin II type 1 receptor antagonist, losartan, causes regression of left ventricular hypertrophy in end-stage renal disease. Nephron. 2002;90:256-61. [PMID: 11867945]
              CrossRefMedlineWeb of Science
            66. 66.↵
              1. TownsendR,
              2. HaggertB,
              3. LissC,
              4. EdelmanJM
              Efficacy and tolerability of losartan versus enalapril alone or in combination with hydrochlorothiazide in patients with essential hypertension.Clin Ther199517911-23pmid:8595643
              Townsend R, Haggert B, Liss C, Edelman JM. Efficacy and tolerability of losartan versus enalapril alone or in combination with hydrochlorothiazide in patients with essential hypertension. Clin Ther. 1995;17:911-23. [PMID: 8595643]
              CrossRefMedlineWeb of Science
            67. 67.↵
              1. Uchiyama-TanakaY,
              2. MoriY,
              3. KishimotoN,
              4. FukuiM,
              5. NoseA,
              6. KijimaY
              et al.Comparison of the effects of quinapril and losartan on carotid artery intima-media thickness in patients with mild-to-moderate arterial hypertension.Kidney Blood Press Res200528111-6pmid:15741734
              Uchiyama-Tanaka Y, Mori Y, Kishimoto N, Fukui M, Nose A, Kijima Y, et al. Comparison of the effects of quinapril and losartan on carotid artery intima-media thickness in patients with mild-to-moderate arterial hypertension. Kidney Blood Press Res. 2005;28:111-6. [PMID: 15741734]
              Medline
            68. 68.↵
              1. VerdecchiaP,
              2. SchillaciG,
              3. ReboldiGP,
              4. SacchiN,
              5. BruniB,
              6. BenemioG
              et al.Long-term effects of losartan and enalapril, alone or with a diuretic, on ambulatory blood pressure and cardiac performance in hypertension: a case-control study.Blood Press Monit20005187-93pmid:10915233
              Verdecchia P, Schillaci G, Reboldi GP, Sacchi N, Bruni B, Benemio G, et al. Long-term effects of losartan and enalapril, alone or with a diuretic, on ambulatory blood pressure and cardiac performance in hypertension: a case-control study. Blood Press Monit. 2000;5:187-93. [PMID: 10915233]
              Medline
            69. 69.↵
              1. RuffD,
              2. GazdickLP,
              3. BermanR,
              4. GoldbergAI,
              5. SweetCS
              Comparative effects of combination drug therapy regimens commencing with either losartan potassium, an angiotensin II receptor antagonist, or enalapril maleate for the treatment of severe hypertension.J Hypertens199614263-70pmid:8728306
              Ruff D, Gazdick LP, Berman R, Goldberg AI, Sweet CS. Comparative effects of combination drug therapy regimens commencing with either losartan potassium, an angiotensin II receptor antagonist, or enalapril maleate for the treatment of severe hypertension. J Hypertens. 1996;14:263-70. [PMID: 8728306]
              CrossRefMedline
            70. 70.↵
              1. TikkanenI,
              2. OmvikP,
              3. JensenHA
              Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension.J Hypertens1995131343-51pmid:8984133
              Tikkanen I, Omvik P, Jensen HA. Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension. J Hypertens. 1995;13:1343-51. [PMID: 8984133]
              MedlineWeb of Science
            71. 71.↵
              1. NielsenS,
              2. DollerupJ,
              3. NielsenB,
              4. JensenHA,
              5. MogensenCE
              Losartan reduces albuminuria in patients with essential hypertension. An enalapril controlled 3 months study.Nephrol Dial Transplant199712SUPPL 219-23pmid:9269694
              Nielsen S, Dollerup J, Nielsen B, Jensen HA, Mogensen CE. Losartan reduces albuminuria in patients with essential hypertension. An enalapril controlled 3 months study. Nephrol Dial Transplant. 1997;12 Suppl 2:19-23. [PMID: 9269694]
              FREE Full Text
            72. 72.↵
              1. AmerenaJ,
              2. PappasS,
              3. OuelletJP,
              4. WilliamsL,
              5. O'ShaughnessyD
              ABPM comparison of the anti-hypertensive profiles of telmisartan and enalapril in patients with mild-to-moderate essential hypertension.J Int Med Res200230543-52pmid:12526280
              Amerena J, Pappas S, Ouellet JP, Williams L, O'Shaughnessy D. ABPM comparison of the anti-hypertensive profiles of telmisartan and enalapril in patients with mild-to-moderate essential hypertension. J Int Med Res. 2002;30:543-52. [PMID: 12526280]
              MedlineWeb of Science
            73. 73.↵
              1. FogariR,
              2. MugelliniA,
              3. ZoppiA,
              4. MarasiG,
              5. PasottiC,
              6. PolettiL
              et al.Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension.Eur J Clin Pharmacol200459863-8pmid:14747881
              Fogari R, Mugellini A, Zoppi A, Marasi G, Pasotti C, Poletti L, et al. Effects of valsartan compared with enalapril on blood pressure and cognitive function in elderly patients with essential hypertension. Eur J Clin Pharmacol. 2004;59:863-8. [PMID: 14747881]
              CrossRefMedlineWeb of Science
            74. 74.↵
              1. LacourcièreY,
              2. NeutelJM,
              3. DavidaiG,
              4. KovalS
              A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure monitoring.Am J Hypertens200619104-12pmid:16461201
              Lacourcière Y, Neutel JM, Davidai G, Koval S. A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure monitoring. Am J Hypertens. 2006;19:104-12. [PMID: 16461201]
              CrossRefMedlineWeb of Science
            75. 75.↵
              1. MallionJM,
              2. BradstreetDC,
              3. MakrisL,
              4. GoldbergAI,
              5. HalaszS,
              6. SweetCS
              et al.Antihypertensive efficacy and tolerability of once daily losartan potassium compared with captopril in patients with mild to moderate essential hypertension.J Hypertens Suppl199513S35-41
              Mallion JM, Bradstreet DC, Makris L, Goldberg AI, Halasz S, Sweet CS, et al. Antihypertensive efficacy and tolerability of once daily losartan potassium compared with captopril in patients with mild to moderate essential hypertension. J Hypertens Suppl. 1995;13:S35-41.
            76. 76.↵
              1. MalmqvistK,
              2. KahanT,
              3. DahlM
              Angiotensin II type 1 (AT1) receptor blockade in hypertensive women: benefits of candesartan cilexetil versus enalapril or hydrochlorothiazide.Am J Hypertens200013504-11pmid:10826401
              Malmqvist K, Kahan T, Dahl M. Angiotensin II type 1 (AT1) receptor blockade in hypertensive women: benefits of candesartan cilexetil versus enalapril or hydrochlorothiazide. Am J Hypertens. 2000;13:504-11. [PMID: 10826401]
              CrossRefMedlineWeb of Science
            77. 77.↵
              1. RagotS,
              2. EzzaherA,
              3. MeunierA,
              4. PoterreM,
              5. BourkaibR,
              6. HerpinD
              Comparison of trough effect of telmisartan vs perindopril using self blood pressure measurement: EVERESTE study.J Hum Hypertens200216865-73pmid:12522468
              Ragot S, Ezzaher A, Meunier A, Poterre M, Bourkaib R, Herpin D. Comparison of trough effect of telmisartan vs perindopril using self blood pressure measurement: EVERESTE study. J Hum Hypertens. 2002;16:865-73. [PMID: 12522468]
              CrossRefMedlineWeb of Science
            78. 78.↵
              1. Roca-CusachsA,
              2. OigmanW,
              3. LepeL,
              4. CifkovaR,
              5. KarpovYA,
              6. HarronDW
              A randomized, double-blind comparison of the antihypertensive efficacy and safety of once-daily losartan compared to twice-daily captopril in mild to moderate essential hypertension.Acta Cardiol199752495-506pmid:9542575
              Roca-Cusachs A, Oigman W, Lepe L, Cifkova R, Karpov YA, Harron DW. A randomized, double-blind comparison of the antihypertensive efficacy and safety of once-daily losartan compared to twice-daily captopril in mild to moderate essential hypertension. Acta Cardiol. 1997;52:495-506. [PMID: 9542575]
              Medline
            79. 79.↵
              1. WilliamsB,
              2. GosseP,
              3. LoweL,
              4. HarperR
              PRISMA I Study GroupThe prospective, randomized investigation of the safety and efficacy of telmisartan versus ramipril using ambulatory blood pressure monitoring (PRISMA I).J Hypertens200624193-200pmid:16331118
              Williams B, Gosse P, Lowe L, Harper R; PRISMA I Study Group. The prospective, randomized investigation of the safety and efficacy of telmisartan versus ramipril using ambulatory blood pressure monitoring (PRISMA I). J Hypertens. 2006;24:193-200. [PMID: 16331118]
              MedlineWeb of Science
            80. 80.↵
              1. HasfordJ,
              2. MimranA,
              3. SimonsWR
              A population-based European cohort study of persistence in newly diagnosed hypertensive patients.J Hum Hypertens200216569-75pmid:12149663
              Hasford J, Mimran A, Simons WR. A population-based European cohort study of persistence in newly diagnosed hypertensive patients. J Hum Hypertens. 2002;16:569-75. [PMID: 12149663]
              CrossRefMedlineWeb of Science
            81. 81.↵
              1. FrankeH
              Antihypertensive effects of candesartan cilexetil, enalapril and placebo.J Hum Hypertens199711SUPPL 2S61-2pmid:9331010
              Franke H. Antihypertensive effects of candesartan cilexetil, enalapril and placebo. J Hum Hypertens. 1997;11 Suppl 2:S61-2. [PMID: 9331010]
              MedlineWeb of Science
            82. 82.↵
              1. RoblesNR,
              2. AnguloE,
              3. GroisJ,
              4. BarqueroA
              Comparative effects of fosinopril and irbesartan on hematopoiesis in essential hypertensives.Ren Fail200426399-404pmid:15462108
              Robles NR, Angulo E, Grois J, Barquero A. Comparative effects of fosinopril and irbesartan on hematopoiesis in essential hypertensives. Ren Fail. 2004;26:399-404. [PMID: 15462108]
              Medline
            83. 83.↵
              1. MazzagliaG,
              2. MantovaniLG,
              3. SturkenboomMC,
              4. FilippiA,
              5. TrifiròG,
              6. CricelliC
              et al.Patterns of persistence with antihypertensive medications in newly diagnosed hypertensive patients in Italy: a retrospective cohort study in primary care.J Hypertens2005232093-100pmid:16208153
              Mazzaglia G, Mantovani LG, Sturkenboom MC, Filippi A, Trifirò G, Cricelli C, et al. Patterns of persistence with antihypertensive medications in newly diagnosed hypertensive patients in Italy: a retrospective cohort study in primary care. J Hypertens. 2005;23:2093-100. [PMID: 16208153]
              Medline
            84. 84.↵
              1. SatoA,
              2. TabataM,
              3. HayashiK,
              4. SarutaT
              Effects of the angiotensin II type 1 receptor antagonist candesartan, compared with angiotensin-converting enzyme inhibitors, on the urinary excretion of albumin and type IV collagen in patients with diabetic nephropathy.Clin Exp Nephrol20037215-20pmid:14586718
              Sato A, Tabata M, Hayashi K, Saruta T. Effects of the angiotensin II type 1 receptor antagonist candesartan, compared with angiotensin-converting enzyme inhibitors, on the urinary excretion of albumin and type IV collagen in patients with diabetic nephropathy. Clin Exp Nephrol. 2003;7:215-20. [PMID: 14586718]
              Medline
            85. 85.↵
              1. GrégoireJP,
              2. MoisanJ,
              3. GuibertR,
              4. CiampiA,
              5. MilotA,
              6. CôtéI
              et al.Tolerability of antihypertensive drugs in a community-based setting.Clin Ther200123715-26pmid:11394730
              Grégoire JP, Moisan J, Guibert R, Ciampi A, Milot A, Côté I, et al. Tolerability of antihypertensive drugs in a community-based setting. Clin Ther. 2001;23:715-26. [PMID: 11394730]
              Medline
            86. 86.↵
              1. MackayFJ,
              2. PearceGL,
              3. MannRD
              Cough and angiotensin II receptor antagonists: cause or confounding?Br J Clin Pharmacol199947111-4pmid:10073748
              Mackay FJ, Pearce GL, Mann RD. Cough and angiotensin II receptor antagonists: cause or confounding? Br J Clin Pharmacol. 1999;47:111-4. [PMID: 10073748]
              CrossRefMedlineWeb of Science
            87. 87.↵
              1. BloomBS
              Continuation of initial antihypertensive medication after 1 year of therapy.Clin Ther199820671-81pmid:9737827
              Bloom BS. Continuation of initial antihypertensive medication after 1 year of therapy. Clin Ther. 1998;20:671-81. [PMID: 9737827]
              CrossRefMedlineWeb of Science
            88. 88.↵
              1. BourgaultC,
              2. SénécalM,
              3. BrissonM,
              4. MarentetteMA,
              5. GrégoireJP
              Persistence and discontinuation patterns of antihypertensive therapy among newly treated patients: a population-based study.J Hum Hypertens200519607-13pmid:15920457
              Bourgault C, Sénécal M, Brisson M, Marentette MA, Grégoire JP. Persistence and discontinuation patterns of antihypertensive therapy among newly treated patients: a population-based study. J Hum Hypertens. 2005;19:607-13. [PMID: 15920457]
              CrossRefMedlineWeb of Science
            89. 89.↵
              1. ConlinPR,
              2. GerthWC,
              3. FoxJ,
              4. RoehmJB,
              5. BoccuzziSJ
              Four-Year persistence patterns among patients initiating therapy with the angiotensin II receptor antagonist losartan versus other artihypertensive drug classes.Clin Ther2001231999-2010pmid:11813934
              Conlin PR, Gerth WC, Fox J, Roehm JB, Boccuzzi SJ. Four-Year persistence patterns among patients initiating therapy with the angiotensin II receptor antagonist losartan versus other artihypertensive drug classes. Clin Ther. 2001;23:1999-2010. [PMID: 11813934]
              CrossRefMedlineWeb of Science
            90. 90.↵
              Degli Esposti L, Degli Esposti E, Valpiani G, Di Martino M, Saragoni S, Buda S, et al. A retrospective, population-based analysis of persistence with antihypertensive drug therapy in primary care practice in Italy. Clin Ther. 2002;24:1347-57; discussion 1346. [PMID: 12240784]
            91. 91.↵
              1. Degli EspostiE,
              2. SturaniA,
              3. Di MartinoM,
              4. FalascaP,
              5. NoviMV,
              6. BaioG
              et al.Long-term persistence with antihypertensive drugs in new patients.J Hum Hypertens200216439-44pmid:12037702
              Degli Esposti E, Sturani A, Di Martino M, Falasca P, Novi MV, Baio G, et al. Long-term persistence with antihypertensive drugs in new patients. J Hum Hypertens. 2002;16:439-44. [PMID: 12037702]
              CrossRefMedlineWeb of Science
            92. 92.↵
              1. ErkensJA,
              2. PannemanMM,
              3. KlungelOH,
              4. van den BoomG,
              5. PrescottMF,
              6. HeringsRM
              Differences in antihypertensive drug persistence associated with drug class and gender: a PHARMO study.Pharmacoepidemiol Drug Saf200514795-803pmid:16178043
              Erkens JA, Panneman MM, Klungel OH, van den Boom G, Prescott MF, Herings RM. Differences in antihypertensive drug persistence associated with drug class and gender: a PHARMO study. Pharmacoepidemiol Drug Saf. 2005;14:795-803. [PMID: 16178043]
              Medline
            93. 93.↵
              1. MarentetteMA,
              2. GerthWC,
              3. BillingsDK,
              4. ZarnkeKB
              Antihypertensive persistence and drug class.Can J Cardiol200218649-56pmid:12107422
              Marentette MA, Gerth WC, Billings DK, Zarnke KB. Antihypertensive persistence and drug class. Can J Cardiol. 2002;18:649-56. [PMID: 12107422]
              MedlineWeb of Science
            94. 94.↵
              1. WogenJ,
              2. KreilickCA,
              3. LivorneseRC,
              4. YokoyamaK,
              5. FrechF
              Patient adherence with amlodipine, lisinopril, or valsartan therapy in a usual-care setting.J Manag Care Pharm20039424-9pmid:14613440
              Wogen J, Kreilick CA, Livornese RC, Yokoyama K, Frech F. Patient adherence with amlodipine, lisinopril, or valsartan therapy in a usual-care setting. J Manag Care Pharm. 2003;9:424-9. [PMID: 14613440]
              Medline
            95. 95.↵
              1. BurkeTA,
              2. SturkenboomMC,
              3. LuSE,
              4. WentworthCE,
              5. LinY,
              6. RhoadsGG
              Discontinuation of antihypertensive drugs among newly diagnosed hypertensive patients in UK general practice.J Hypertens2006241193-200pmid:16685222
              Burke TA, Sturkenboom MC, Lu SE, Wentworth CE, Lin Y, Rhoads GG. Discontinuation of antihypertensive drugs among newly diagnosed hypertensive patients in UK general practice. J Hypertens. 2006;24:1193-200. [PMID: 16685222]
              MedlineWeb of Science
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