Statin Therapy in the Prevention of Recurrent Cardiovascular Events: A Sex-Based Meta-Analysis

Study Questions:

Does statin-associated protection against recurrent cardiovascular events differ by gender?


This meta-analysis included randomized clinical trials, identified through PubMed, including only trials that focused on secondary prevention. Previous cardiovascular disease was defined as prior myocardial infarction (MI), angina (stable or unstable), any cardiac intervention, any stroke or transient ischemic attack, peripheral arterial disease, or more than three cardiovascular risk factors. Only clinical trials were included and only if they met the following criteria: random allocation to the groups, double-blinding, placebo-control, follow-up of at least 16 weeks, sample size of at least 100 total participants, and outcomes reported by sex in both active and control groups. Studies with an open-label design and observational studies were excluded. From 878 citations identified, 609 were excluded, leaving 269 reviewed, from which 11 separate studies were identified and included.


From these 11 studies, a total of 43,193 patients were included in this analysis. Follow-up of these studies ranged from 16 weeks to 6.1 years, with 2 or more years for eight of the studies. All the studies demonstrated reductions in rates of any cardiovascular events with statin therapy; however, the results were less consistent for women than for men. Overall, statin therapy was associated with a reduced risk of cardiovascular events in all outcomes for women (relative risk [RR], 0.81; 95% confidence interval [CI], 0.74-0.89) and men (RR, 0.82; 95% CI, 0.78-0.85). No statin-related benefit was observed for women for all-cause mortality (RR, 0.92; 95% CI, 0.76-1.13), while a benefit was observed for men (RR, 0.79; 95% CI, 0.72-0.87). A similar pattern was observed for stroke, with no benefit noted for women (RR, 0.92; 95% CI, 0.76-1.10) and a significant benefit noted for men (RR, 0.81; 95% CI, 0.72-0.92). For the outcomes of MI, coronary mortality, and cardiac interventions, statin therapy was similarly protective for women compared to men. Mean differences in lipid profiles were pooled across studies, which demonstrated similar statin-associated changes in lipid profiles for men and women.


The authors concluded that statin therapy is an effective intervention for secondary prevention of cardiovascular events in both men and women; however, no benefit of statins was observed for stroke and all-cause mortality among women.


This meta-analysis supports current recommendations for statin therapy in secondary prevention for women. Further research specifically on the long-term use of statins, and with long-term follow-up, may provide data regarding the specific outcomes in women that may occur later in life.

Clinical Topics: Dyslipidemia, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Nonstatins, Novel Agents, Statins

Keywords: Myocardial Infarction, Stroke, Follow-Up Studies, PubMed, Ischemic Attack, Transient, Secondary Prevention, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiovascular Diseases, Peripheral Arterial Disease, Risk Factors, Confidence Intervals

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