Clinical Question: Is statin therapy effective in preventing cardiac events?

Bottom Line: In this analysis of patient data pooled from multiple studies, intensive statin therapy was more effective than less intensive statin therapy in reducing the rate of major cardiovascular events. Additionally, statins are more effective than controls in preventing major cardiovascular events. In spite of the authors' attempts to link these data to low-density lipoprotein (LDL) concentrations, none of the trials randomly assigned patients to specific LDL targets. (Level of Evidence: 1a)

Reference: Cholesterol Treatment Trialists' (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376(9753):1670-1681.

Study Design: Meta-analysis (randomized controlled trials)

Funding Source: Government

Allocation: Concealed

Setting: Outpatient (any)

Synopsis: These authors pooled the patient-level data from 26 studies each involving at least 1000 patients and having at least 2 years of follow-up. Five of the trials compared intensive statin therapy with less intensive statin therapy and 21 compared statins with controls. Of the 5 trials comparing statin intensity, 2 evaluated 8659 patients with acute coronary syndromes (2.1 years of follow-up) and 3 evaluated 30,953 patients with stable coronary artery disease (5.8 years of follow-up). After 1 year of treatment, the LDL cholesterol levels decreased by an average 0.51 mmol/L (20 mg/dL). The annual rate of major vascular events (cardiovascular death, nonfatal myocardial infarction, revascularization, or stroke) was 4.5% in the intensive therapy group and 5.3% in the less intense therapy group (number needed to treat [NNT] = 200 per year). Of the 14 trials comparing statin therapy with control (128,596 patients with 4.8 years of follow-up), 6 appear to be primary prevention studies and the remainder were for secondary prevention. In these 14 studies, after 1 year of treatment the LDL cholesterol levels decreased by 1.07 mmol/L (41 mg/dL). The annual rate of major vascular events was 2.8% in the patients taking statins compared with 3.6% in patients taking a control agent (NNT = 125 per year). Although they don't report the annual rate of death from any cause for each treatment group, the authors report the total death rate for the intensively treated patients plus the statin-treated patients (2.1%) compared with the rate of the less intensively treated patients plus control patients (2.3%). This works out to a number needed to treat of 500 per year.The authors also try to correlate the outcomes data with the LDL levels achieved by the various interventions. However, since none of the trials actually randomized patients to specific lipid targets, this information should be interpreted cautiously and is best used to generate hypotheses. If you subscribe to the lipid theory of atherogenesis, you will love this part of the study. If you subscribe to alternate theories (eg, inflammation, plaque stability, and so forth) or are a methodologic purist, you will be annoyed by the authors' extrapolations.