Patients with ischemic heart disease and preserved ventricular function experience considerable morbidity and mortality despite standard medical therapy.
To compare benefits and harms of using angiotensin-converting enzyme (ACE) inhibitors, angiotensin II–receptor blockers (ARBs), or combination therapy in adults with stable ischemic heart disease and preserved ventricular function.
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (earliest date, July 2009) were searched without language restrictions.
Two independent investigators screened citations for trials of at least 6 months' duration that compared ACE inhibitors, ARBs, or combination therapy with placebo or active control and reported any of several clinical outcomes.
Using standardized protocols, 2 independent investigators extracted information about study characteristics and rated the quality and strength of evidence. Disagreement was resolved by consensus.
41 studies met eligibility criteria. Moderate- to high-strength evidence (7 trials; 32 559 participants) showed that ACE inhibitors reduce the relative risk (RR) for total mortality (RR, 0.87 [95% CI, 0.81 to 0.94]) and nonfatal myocardial infarction (RR, 0.83 [CI, 0.73 to 0.94]) but increase the RR for syncope (RR, 1.24 [CI, 1.02 to 1.52]) and cough (RR, 1.67 [CI, 1.22 to 2.29]) compared with placebo. Low-strength evidence (1 trial; 5926 participants) suggested that ARBs reduce the RR for the composite end point of cardiovascular mortality, nonfatal myocardial infarction, or stroke (RR, 0.88 [CI, 0.77 to 1.00]) but not for the individual components. Moderate-strength evidence (1 trial; 25 620 participants) showed similar effects on total mortality (RR, 1.07 [CI, 0.98 to 1.16]) and myocardial infarction (RR, 1.08 [CI, 0.94 to 1.23]) but an increased risk for discontinuations because of hypotension (P < 0.001) and syncope (P = 0.035) with combination therapy compared with ACE inhibitors alone.
Many studies either did not assess or did not report harms in a systematic manner. Many studies did not adequately report benefits or harms by various patient subgroups.
Adding an ACE inhibitor to standard medical therapy improves outcomes, including reduced risk for mortality and myocardial infarctions, in some patients with stable ischemic heart disease and preserved ventricular function. Less evidence supports a benefit of ARB therapy, and combination therapy seems no better than ACE inhibitor therapy alone and increases harms.
Agency for Healthcare Research and Quality.
Trials demonstrate the efficacy of medications to reduce the risk for invasive breast cancer.
To summarize benefits and harms of tamoxifen citrate, raloxifene, and tibolone to reduce the risk for primary breast cancer.
MEDLINE and Cochrane databases from inception to January 2009, Web of Science, trial registries, and manufacturer information.
Predefined eligibility criteria were used to select articles. English-language reports of randomized, controlled trials (RCTs) for benefits and RCTs and observational studies for harms were included.
Two reviewers assessed study data, quality, and applicability.
Seven placebo-controlled RCTs and 1 head-to-head trial provide results for main outcomes. Tamoxifen (risk ratio, 0.70 [95% CI, 0.59 to 0.82]; 4 trials), raloxifene (risk ratio, 0.44 [CI, 0.27 to 0.71]; 2 trials), and tibolone (risk ratio, 0.32 [CI, 0.13 to 0.80]; 1 trial) reduce risk for invasive breast cancer compared with placebo by 7 to 10 per 1000 women per year. Tamoxifen and raloxifene reduce estrogen receptor–positive breast cancer but not estrogen receptor–negative breast cancer, noninvasive breast cancer, or mortality. All medications reduce fractures. Tamoxifen (risk ratio, 1.93 [CI, 1.41 to 2.64]; 4 trials) and raloxifene (risk ratio, 1.60 [CI, 1.15 to 2.23]; 2 trials) increase thromboembolic events by 4 to 7 per 1000 women per year; raloxifene causes fewer events than tamoxifen. Tamoxifen increases risk for endometrial cancer (risk ratio, 2.13 [CI, 1.36 to 3.32]; 3 trials) compared with placebo by 4 per 1000 women per year and causes cataracts compared with raloxifene. Tibolone causes strokes in older women.
Bias, trial heterogeneity, and a dearth of head-to-head trials limit this review. Data are lacking on doses, duration, and timing of the medications; long-term effects; and nonwhite and premenopausal women.
Three medications reduce risk for primary breast cancer but increase risk for thromboembolic events (tamoxifen, raloxifene), endometrial cancer (tamoxifen), or stroke (tibolone).
Agency for Healthcare Research and Quality.
Statin therapy effectively prevents vascular disease, but treatment targets are often not achieved.
To compare the benefits and harms of high-dose statin monotherapy with those of combination therapy in adults at high risk for coronary disease.
English-language records from MEDLINE (1966 to 2009), EMBASE (1980 to 2009), and the Cochrane Library (third quarter of 2008).
A reviewer screened records, and a second reviewer verified selection of randomized, controlled trials in adult patients that compared combinations of statins and bile-acid sequestrants, fibrates, ezetimibe, niacin, or -3 fatty acids with statin monotherapy, as well as nonrandomized comparative studies that were longer than 24 weeks and reported clinical and harms outcomes.
Data were abstracted for studies by using standardized forms, and study quality was rated with a standardized scale and strength of evidence by using the Grading of Recommendations Assessment, Development, and Evaluation approach.
102 studies met eligibility criteria. The main analysis compared combination therapy with high-dose statin monotherapy in high-risk patients. Very-low-strength evidence showed that statin–ezetimibe (2 trials; n = 439) and statin–fibrate (1 trial; n = 166) combinations did not reduce mortality more than high-dose statin monotherapy. No trials compared the effect of combination therapy versus high-dose statin monotherapy on the incidence of myocardial infarction, stroke, or revascularization procedures. Two statin–ezetimibe trials (n = 295) demonstrated higher low-density lipoprotein cholesterol goal attainment with combination therapy (odds ratio, 7.21 [95% CI, 4.30 to 12.08]). Trials in lower-risk patients did not show a difference in mortality.
Studies were generally short, focused on surrogate outcomes, and were heterogeneous in the sample's risk for coronary disease. Few studies examined treatment combinations other than statin–ezetimibe.
Limited evidence suggests that combinations of lipid-lowering agents do not improve clinical outcomes more than high-dose statin monotherapy. Very-low-quality evidence favors statin–ezetimibe treatment for attainment of low-density lipoprotein cholesterol goals.
Agency for Healthcare Research and Quality.
Intravenous sodium bicarbonate has been proposed to reduce the risk for contrast-induced nephropathy (CIN).
To determine the effect of sodium bicarbonate on the risk for CIN.
MEDLINE, PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from 1950 to December 2008; conference proceedings; and ClinicalTrials.gov, without language restriction.
Randomized, controlled trials of intravenous sodium bicarbonate that prespecified the outcome of CIN as a 25% increase in baseline serum creatinine level or an absolute increase of 44 µmol/L (0.5 mg/dL) after radiocontrast administration.
Using standardized protocols, 2 reviewers serially abstracted data for each study.
23 published and unpublished trials with information on 3563 patients and 396 CIN events were included. The pooled relative risk was 0.62 (95% CI, 0.45 to 0.86), with evidence of significant heterogeneity across studies (I 2 = 49.1%; P = 0.004). Some heterogeneity was due to the difference in the estimates between published and unpublished studies: relative risk, 0.43 (CI, 0.25 to 0.75) versus 0.78 (CI, 0.52 to 1.17), respectively. Meta-regression showed that small, poor-quality studies that assessed outcomes soon after radiocontrast administration were more likely to suggest benefit (P < 0.05 for all). No clear effects of treatment on the risk for dialysis, heart failure, and total mortality were identified.
Power to assess clinical end points was limited.
The effectiveness of sodium bicarbonate treatment to prevent CIN in high-risk patients remains uncertain. Earlier reports probably overestimated the magnitude of any benefit, whereas larger, more recent trials have had neutral results. Large multicenter trials are required to clarify whether sodium bicarbonate has value for prevention of CIN before routine use can be recommended.
None.