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.
Purpose: To review evidence about the benefits and harms of charged-particle radiation therapy for patients with cancer.
Data Sources: MEDLINE (inception to 11 July 2009) was searched for publications in English, German, French, Italian, and Japanese. Web sites of manufacturers, treatment centers, and professional organizations were searched for relevant information.
Study Selection: Four reviewers identified studies of any design that described clinical outcomes or adverse events in 10 or more patients with cancer treated with charged-particle radiation therapy.
Data Extraction: The 4 reviewers extracted study, patient, and treatment characteristics; clinical outcomes; and adverse events for nonoverlapping sets of articles. A fifth reviewer verified data on comparative studies.
Data Synthesis: Currently, 7 centers in the United States have facilities for particle (proton)–beam irradiation, and at least 4 are under construction, each costing between $100 and $225 million. In 243 eligible articles, charged-particle radiation therapy was used alone or in combination with other interventions for common (for example, lung, prostate, or breast) or uncommon (for example, skull-base tumors or uveal melanomas) types of cancer. Of 243 articles, 185 were single-group retrospective studies. Eight randomized and 9 nonrandomized clinical trials compared treatments with or without charged particles. No comparative study reported statistically significant or important differences in overall or cancer-specific survival or in total serious adverse events.
Limitation: Few studies directly compared treatments with or without particle irradiation.
Conclusion: Evidence on the comparative effectiveness and safety of charged-particle radiation therapy in cancer is needed to assess the benefits, risks, and costs of treatment alternatives.
Primary Funding Source: Agency for Healthcare Research and Quality.
]]>Purpose: To determine whether ventilation with low tidal volume (V
Data Sources: Multiple computerized databases (through March 2009), reference lists of identified articles, and queries of principal investigators. No language restrictions were applied.
Study Selection: Randomized, controlled trials (RCTs) reporting mortality and comparing lower versus higher V
Data Extraction: Using a standard protocol, 2 reviewer teams assessed trial eligibility and abstracted data on quality of study design and conduct, population characteristics, intervention, co-interventions, and confounding variables.
Data Synthesis: 4 RCTs tested lower versus higher V
Limitations: Pooling according to similar ventilatory strategies resulted in few RCTs analyzed in each group. The benefit of low V
Conclusion: Available evidence from a limited number of RCTs shows better outcomes with routine use of low V
Primary Funding Source: None.
]]>Purpose: To evaluate the safety and efficacy of extended-duration (>4 weeks) NAI chemoprophylaxis against influenza.
Data Sources: Studies published in any language through 11 June 2009 identified by searching 10 electronic databases and 3 trial registries.
Study Selection: Randomized, placebo-controlled, double-blind human trials of extended-duration NAI chemoprophylaxis that reported outcomes of laboratory-confirmed influenza or adverse events.
Data Extraction: 2 reviewers independently assessed study quality and abstracted information from eligible studies.
Data Synthesis: Of 1876 potentially relevant citations, 7 trials involving 7021 unique participants met inclusion criteria. Data were pooled by using random-effects models. Chemoprophylaxis with NAIs decreased the frequency of symptomatic influenza (relative risk [RR], 0.26 [95% CI, 0.18 to 0.37]; risk difference [RD], –3.9 percentage points [CI, –5.8 to –1.9 percentage points]) but not asymptomatic influenza (RR, 1.03 [CI, 0.81 to 1.30]; RD, –0.4 percentage point [CI, –1.6 to 0.9 percentage point]). Adverse effects were not increased overall among NAI recipients (RR, 1.01 [CI, 0.94 to 1.08]; RD, 0.1 percentage point [CI, –0.2 to 0.4 percentage point]), but nausea and vomiting were more common among those who took oseltamivir (RR, 1.48 [CI, 1.86 to 2.33]; RD, 1.7 percentage points [CI, 0.6 to 2.9 percentage points]). Prevention of influenza did not statistically significantly differ between zanamivir and oseltamivir.
Limitations: All trials were industry-sponsored. No study was powered to detect rare adverse events, and none included diverse racial groups, children, immunocompromised patients, or individuals who received live attenuated influenza virus vaccine.
Conclusion: Extended-duration zanamivir and oseltamivir chemoprophylaxis seems to be highly efficacious for preventing symptomatic influenza among immunocompetent white and Japanese adults. Extended-duration oseltamivir is associated with increased nausea and vomiting. Safety and efficacy in several subpopulations that might receive extended-duration influenza chemoprophylaxis are unknown.
]]>Purpose: To summarize clinical benefits and harms of intensive versus conventional glucose control for adults with type 2 diabetes.
Data Sources: Studies were retrieved by systematically searching the MEDLINE database (January 1950 to April 2009) with no language restrictions.
Study Selection: Two independent reviewers screened abstracts or full-text articles to identify randomized trials that compared clinical outcomes in patients with type 2 diabetes receiving intensive glucose control and those receiving conventional glucose control.
Data Extraction: Two investigators independently abstracted data on study variables and outcomes, including severe hypoglycemia, cardiovascular disease, and all-cause mortality.
Data Synthesis: 5 trials involving 27 802 adults were included. Intensive glucose targets were lower in the 3 most recent trials. Summary analyses showed that compared with conventional control, intensive glucose control reduced the risk for cardiovascular disease (relative risk [RR], 0.90 [95% CI, 0.83 to 0.98]; risk difference per 1000 patients per 5 years [RD], –15 [CI, –24 to –5]) but not cardiovascular death (RR, 0.97 [CI, 0.76 to 1.24]; RD, –3 [CI, –14 to 7]) or all-cause mortality (RR, 0.98 [CI, 0.84 to 1.15]; RD, –4 [CI, –17 to 10]). Intensive glucose control increased the risk for severe hypoglycemia (RR, 2.03 [CI, 1.46 to 2.81]; RD, 39 [CI, 7 to 71]). As was seen in the overall analyses, pooled findings from the early and more recent trials showed that intensive glucose control reduced the risk for cardiovascular disease and increased the risk for severe hypoglycemia.
Limitation: Summary rather than individual data were pooled across trials.
Conclusion: Intensive glucose control reduced the risk for some cardiovascular disease outcomes (such as nonfatal myocardial infarction), did not reduce the risk for cardiovascular death or all-cause mortality, and increased the risk for severe hypoglycemia.
]]>Purpose: To determine the association between retinal vessel caliber and risk for CHD.
Data Sources: Relevant studies in any language identified through MEDLINE (1950 to June 2009) and EMBASE (1950 to June 2009) databases.
Study Selection: Studies were included if they examined a general population, measured retinal vessel caliber from retinal photographs, and documented CHD risk factors and incident CHD events.
Data Extraction: 6 population-based prospective cohort studies provided data for individual participant meta-analysis.
Data Synthesis: Proportional hazards models, adjusted for traditional CHD risk factors, were constructed for retinal vessel caliber and incident CHD in women and men. Among 22 159 participants who were free of CHD and followed for 5 to 14 years, 2219 (10.0%) incident CHD events occurred. Retinal vessel caliber changes (wider venules and narrower arterioles) were each associated with an increased risk for CHD in women (pooled multivariable-adjusted hazard ratios, 1.16 [95% CI, 1.06 to 1.26] per 20-µm increase in venular caliber and 1.17 [CI, 1.07 to 1.28] per 20-µm decrease in arteriolar caliber) but not in men (1.02 [CI, 0.94 to 1.10] per 20-µm increase in venular caliber and 1.02 [CI, 0.95 to 1.10] per 20-µm decrease in arteriolar caliber). Women without hypertension or diabetes had higher hazard ratios.
Limitation: Error in the measurement of retinal vessel caliber and Framingham variables was not taken into account.
Conclusion: Retinal vessel caliber changes were independently associated with an increased risk for CHD events in women.
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