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Review Article |

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

Jose Gutierrez, MD, MPH; Gilbert Ramirez, PhD; Tatjana Rundek, MD, PhD; Ralph L. Sacco, MD, MS
Arch Intern Med. 2012;172(12):909-919. doi:10.1001/archinternmed.2012.2145.
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Published online

Background  The effect of statins on the prevention of cardiovascular events is well demonstrated. Whether this protective effect is equal for women and men remains less well established. Our objective was to evaluate if statin therapy is equally effective in decreasing recurrent cardiovascular events in women and men.

Data Sources  Randomized clinical trials were searched in PubMed using as indexing terms (statins OR cholesterol lowering medications) AND (cardiovascular events OR stroke OR myocardial infarction OR cardiovascular death).

Study Selection  We included randomized, double-blinded, placebo-controlled trials evaluating statins for secondary prevention of cardiovascular events. Studies with an open-label design and observational studies were excluded.

Data Extraction  The earliest citation was used to determine the characteristic of the studied population and the methodology. All subsequent citations corresponding to the trial were evaluated for outcome rates by sex.

Data Synthesis  Eleven trials representing 43 193 patients were included in the analysis. Overall, statin therapy was associated with a reduced risk of cardiovascular events in all outcomes for women (relative risk [RR], 0.81 [95% CI, 0.74-0.89]) and men (RR, 0.82 [95% CI, 0.78-0.85]). However, they did not reduce all-cause mortality in women vs men (RR, 0.92 [95% CI, 0.76-1.13] vs RR, 0.79 [95% CI, 0.720.87]) or stroke (RR, 0.92 [95% CI, 0.76-1.10] vs RR, 0.81 [95% CI, 0.72-0.92]).

Conclusions  Statin therapy is an effective intervention in the secondary prevention of cardiovascular events in both sexes, but there is no benefit on stroke and all-cause mortality in women.

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Figures

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Figure 1. Study flowchart. Please note, there is no conflict between the 68 citations noted in the figure to be included in the analysis and the fewer citations present in this article. All pertinent information from the relevant trials was obtained from the articles cited herein.

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Figure 2. Any cardiovascular event (cardiac and/or cerebrovascular). Risk ratios are based on the fixed Mantel-Haentzl test analysis. ASCOT-LLA indicates Anglo-Scandinavian Cardiac Outcomes Trial–lipid-lowering arm2427; CARE, Cholesterol and Recurrent Events trial50; CCAIT, Canadian Coronary Atherosclerosis Intervention Trial3738; FLORIDA, Fluvastatin on Risk Diminishment After Acute Myocardial Infarction trial23; Fluvastatin on CE, Fluvastatin on Cardiac Events52; LIPID, Long-Term Intervention with Pravastatin in Ischaemic Disease2836; M-H, Mantel-Haentzl test; MIRACL, Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering study1319; PLAC-I, Pravastatin Limitation of Atherosclerosis in the Coronary Arteries trial51; PROSPER, Prospective Study of Pravastatin in the Elderly at Risk4849; SPARCL, Stroke Prevention by Aggressive Reduction in Cholesterol Levels Study712; 4S, Scandinavian Simvastatin Survival Study.28,3947

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Figure 3. All-cause mortality. For all abbreviations, data explanation, and study references, see legend to Figure 2.

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Figure 4. Any stroke (fatal or nonfatal). For all abbreviations, data explanation, and study references, see legend to Figure 2.

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