Clinical Question: Does statin therapy for primary and secondary prevention of cardiovascular disease among patients with elevated low-density lipoprotein levels reduce all-cause mortality?

Bottom Line: Statins reduce all-cause mortality among patients with hyperlipidemia, whether used for primary or secondary prevention of cardiovascular disease. This is a class effect. (Level of Evidence: 1a)

Reference: Mills EJ, Wu P, Chong G, et al. Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. QJM 2011;104(2):109-124.

Study Design: Meta-analysis (randomized controlled trials)

Funding Source: Unknown/not stated

Setting: Various (meta-analysis)

Synopsis: This is a methodologically thorough meta-analysis of 76 randomized trials, including 170,255 patients, in which a statin was compared with placebo, standard therapy, or no treatment for primary or secondary prevention of cardiovascular disease (CVD). The authors included all identified randomized controlled trials of atorvastatin, fluvastatin, lovastatin, pitavastatin, rosuvastatin, and simvastatin. Head-to-head trials of statins were excluded. Women comprised 26% of study participants. The mean low-density lipoprotein (LDL) level at baseline was 180 mg/dL. Trials ranged in duration from 6 months to 6.1 years (mean = 2.7 years). The all-cause mortality rate was 8.1% in the statin groups and 9.5% in the control groups (relative risk [RR] = 0.90; 95% CI, 0.86-0.94; P < .0001; number needed to treat [NNT] = 67). A dose-response relationship was found with change in absolute LDL levels and did not differ between statins in univariate analysis; however, this effect was not observed in the multiple regression analysis. The reduction in all-cause mortality was largely attributable to a reduction in CVD deaths (4.1% vs 5.1%; RR = 0.80; 0.74-0.87; P < .001; NNT = 100). There were significant reductions in death due to myocardial infarction, and nonsignificant reductions in deaths due to stroke and non-CVD causes. Incident cancers and rhabdomyolosis were not significantly increased in statin groups. There was a slight increase in new incident diabetes (3.8% vs 3.5%; odds ratio = 1.09; 1.02-1.16; P = .008. Although relative risk reduction was consistent among primary prevention and secondary prevention populations, the absolute risk reduction would not be similar (absolute risk reduction was not reported).