Statins for primary cardiovascular prevention

Background: Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in persons with and without a history of coronary heart disease (CHD), is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in persons with coronary artery disease. The case for primary prevention, however, is less clear. SA Objectives: To assess the effects, both harms and benefits, of statins in persons with no history of CVD. Search Strategy: To avoid duplication of effort, we checked reference lists of previous systematic reviews. We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2007), Medline (2001 to March 2007), and EMBASE (2003 to March 2007). There were no language restrictions. Selection Criteria: Randomized controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total low-density lipoprotein or high-density lipoprotein cholesterol levels, and where 10 percent or less had a history of CVD, were included. Data Collection and Analysis: Two authors independently selected studies for inclusion and extracted data. Outcomes included all-cause mortality, fatal and nonfatal CHD, CVD and stroke events, combined end points (fatal and nonfatal CHD, CVD, and stroke events), change in blood total cholesterol concentration, revascularization, adverse events, quality of life, and costs. Relative risk (RR) was calculated for dichotomous data, and for continuous data pooled weighted mean differences (with 95% confidence intervals [CIs]) were calculated. Main Results: Fourteen randomized controlled trials (16 trial arms; 34,272 participants) were included. Eleven trials recruited patients with specific conditions (raised lipids, diabetes mellitus, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR = 0.83; 95% CI, 0.73 to 0.95), as were combined fatal and nonfatal CVD end points (RR = 0.70; 95% CI, 0.61 to 0.79). Benefits were also seen in the reduction of revascularization rates (RR = 0.66; 95% CI, 0.53 to 0.83). Total cholesterol and low-density lipoprotein cholesterol levels were reduced in all trials but there was evidence of heterogeneity of effects. There was no clear evidence of any significant harm caused by statin prescription or of effects on patient quality of life. Authors' Conclusions: Although reductions in all-cause mortality, composite end points, and revascularizations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events, and inclusion of persons with CVD. Only limited evidence showed that primary prevention with statins may be cost-effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention in persons at low cardiovascular risk.