Sex-Specific Benefits to Statin Therapy in Preventing CV Events

Statin therapy is commonly used to lower serum cholesterol levels and aid in the prevention of cardiovascular events. Previous statin trials have predominately enrolled men, according to researchers, and there have been conflicting results on the benefits of statin therapy for women with cardiovascular disease compared with men in preventing secondary cardiovascular events. The American Heart Association recently released guidelines recommending statin therapy to achieve the same low-density lipoprotein goals for women and men.

The researchers recently conducted a sex-based meta-analysis to determine if statin therapy is equally effective in preventing the recurrence of cardiovascular events and all-cause mortality in men and women; the researchers also aimed to determine the sex-specific effects of statins on the risk of recurrent cardiac and cerebrovascular events. Results were reported in Archives of Internal Medicine [2012;172(12):909-919].

The researchers searched PubMed for randomized clinical trials using the search terms statins or cholesterol lowering medications and cardiovascular events or stroke or myocardial infarction or cardiovascular death. Search results were limited to humans, male, female, clinical trials, English language, and all adults >19 years of age from date of inception until September 15, 2010.

The initial search revealed 878 PubMed citations. After applying inclusion and exclusion criteria, the researchers excluded 609 of the 878. Following text reading of the 269 remaining citations, 201 were excluded (111 studies), resulting in 68 citations (11 studies) in the final analysis.

The 11 trials included in the analysis represented 43,193 patients; 20.6% were female. All of the studies demonstrated efficacy of statins in the reduction of the rate of any cardiovascular events. The results were less consistent for women than for men, however, when stratified by sex.

None of the trials (n=5) evaluating all-cause mortality found statistically significant risk reduction in women who were taking statins; for men, 2 of the 5 trials found significant risk reduction in mortality rate.

There were 3 trials that identified coronary mortality; all 3 found significant risk reduction for men, but only the CARE (Cholesterol and Recurrent Events) trial showed a risk reduction for women.

Overall, the trials found that statins were effective in preventing any cardiovascular event compared with placebo (relative risk [RR], 0.81; 95% confidence interval [CI], 0.78-0.85). The sex-specific analysis did not change the direction or significance of the risk reduction: for women, RR, 0.81; 95% CI, 0.74-0.89 versus RR, 0.82; 95% CI, 0.78-0.85 for men.

Statins were superior to placebo in reducing all-cause mortality (RR, 0.81; 95% CI, 0.75-0.88); however, the statin benefit in women was not statistically significant (RR, 0.92; 95% CI, 0.76-1.13). The benefit did reach statistical significance in men (RR, 0.79; 95% CI, 0.72-0.87).

Overall, statins were effective in preventing recurrence of stroke compared with placebo (RR, 0.84; 95% CI, 0.76-0.93). Sex-specific stratification showed a similar statistically significant benefit in men (RR, 0.81; 95% CI, 0.72-0.92), but not in women (RR, 0.92; 95% CI, 0.76-1.10).

Limitations to the analysis cited by the authors included possible bias due to use of only 1 database and the small percentage of women represented in the analyzed trials.

In summary, the researchers stated, “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.”