Reducing Cardiovascular Disease Risk in Women Beyond Statin Therapy: New Insights 2020

Abstract

Management of residual and persistent cardiovascular disease (CVD) risk among statin-treated individuals has emerged as an important preventive strategy. The purpose of this article is to review the unique landscape of CVD in women and relevant prior prevention trials, and to discuss how the recent results of the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) might apply to the contemporary management of CVD risk among statin-treated women. Women have unique risk factors that may impact CVD and its prevention. Historically, women have been underrepresented in CVD trials, posing a challenge to development of clinical recommendations for women. Low-density lipoprotein cholesterol-targeting treatments have demonstrated CVD risk reduction, with comparable effects in both sexes. In contrast, triglyceride-lowering treatments (niacin, fenofibrate, and omega-3 fatty acids) have reported mixed findings for CVD risk reduction. Recent clinical trials of combination omega-3 fatty acids (docosahexaenoic acid/eicosapentaenoic acid [EPA]) have not found significant CVD risk reduction. The recently published REDUCE-IT study found that icosapent ethyl, an EPA-only omega-3 fatty acid, in combination with statins, significantly reduced CVD events in high-risk patients. The icosapent ethyl group had a significantly lower occurrence of the primary composite CVD endpoint (17.2%) than the placebo group (22.0%; hazard ratio 0.75; 95% confidence interval 0.68-0.83; p < 0.001). CVD risk reduction with icosapent ethyl treatment was comparable between women and men (p for interaction, 0.33). Data from REDUCE-IT suggest women benefit similarly to men with respect to icosapent ethyl, a novel therapy for prevention of CVD.

Keywords: cardiovascular disease; eicosapentaenoic acid; icosapent ethyl; sex differences; women.

FIG. 1.

Change in cardiovascular deaths in men and women since 1979. Reprinted with permission, Benjamin et al., ©2019 American Heart Association, Inc.

FIG. 2.

Cumulative incidence of cardiovascular events in REDUCE-IT. Kaplan-Meier event curves for the primary efficacy endpoint, defined as a composite of CVD death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina in a time-to-event analysis (A); and the key secondary endpoint, defined as a composite of CVD death, nonfatal MI, or nonfatal stroke in a time-to-event analysis (B). In each panel, the inset shows the same data on an expanded y axis. The curves were visually truncated at 5.7 years because a limited number of events occurred beyond that time point; all patient data were included in the analyses. CVD, cardiovascular disease; MI, myocardial infarction; REDUCE-IT, Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial. From Bhatt et al., ©2019 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.