Clinical Question: Are statins effective in preventing coronary artery disease?

Setting: Outpatient (any)

Study Design: Meta-analysis (randomized controlled trials)

Synopsis: The investigators from 14 major trials of lipid-lowering medications that used statins pooled the data on 90,056 patients to provide more robust information on individual outcomes. Nine of the trials were secondary prevention studies. The median follow-up was 4.7 years (range = two to six years). Overall, the studies were composed mostly of men; approximately 21 percent had diabetes, and 54 percent had cardiovascular disease. In other words, about one out of five adults in the United States would have been eligible to participate in these studies. Statins decreased all-cause mortality (8.5 versus 9.6 percent; number needed to treat [NNT] = 86; 95% confidence interval [CI], 65 to 126). The authors report that this translated to a 12 percent relative reduction for every mmol per L of low-density lipoprotein cholesterol reduction. Similarly, statins reduced cardiovascular death (3.4 versus 4.4 percent; NNT = 109; 95% CI, 86 to 150). The rate of major coronary events was lower with statins (NNT = 42; 95% CI, 36 to 49), as were the rates of revascularizations (NNT = 56; 95% CI, 47 to 68) and strokes (NNT = 162; 95% CI, 118 to 259). Additionally, statins were beneficial regardless of age or sex, although the magnitude of benefit was greater for patients younger than 65 years (NNT = 68; 95% CI, 57 to 82). Patients 65 years or older had an NNT of 111 and a 95% CI of 86 to 155. Benefits also were greater for men (NNT= 48; 95% CI, 42 to 57). Women had an NNT of 326 and a 95% CI of 213 to 700.

Although reductions in major coronary events were reported within the first year, they were greater with longer use and were proportional to the absolute risk at baseline. In other words, the highest-risk patients derive the greatest benefit. These pooled data also did not find any association with developing in total or site-specific incident cancers. After five years, 0.01 percent more patients using statins will develop rhabdomyolysis (P = .4). The authors do not report on pooled dropout rates or how many patients experience liver failure, hepatic enzyme elevation, myalgias, or arthralgias.

Bottom Line: Statins reduce five-year overall mortality and specifically decrease cardiovascular mortality and morbidity. The patients at highest baseline risk derive the greatest benefit. A word of caution: most, if not all, of these trials used targeted doses of statins and did not randomize patients to specific lipid levels. Because the effects of statins may be independent of their lipid-lowering effect, using the lipid levels inferred from these trials should be done with caution. (Level of Evidence: 1a)