Should There Be a Different Cardiovascular Prevention Polypill Strategy for Women and Men? Mark D. Huffman & Mohammed K. Ali & K. M. Venkat Narayan Published online: 12 February 2011 # Springer Science+Business Media, LLC 2011 Abstract The concept of a polypill for cardiovascular disease prevention has attracted widespread attention since Wald and Law’s seminal paper in 2003. The authors estimated > 80% reduction in coronary heart disease and stroke deaths through mass application of a polypill in people aged 55 years and older. Although their proposition has been subject to criticisms and heated debate regarding side effects, efficacy, and appropriateness of the interven- tion, few have discussed the differential risks and benefits of a polypill for women and men and whether sex-specific polypill strategies should be developed. In this review, we discuss the benefits and drawbacks of sex-specific polypill strategies by evaluating the published literature regarding 1) sex differences in cardiovascular risk and risk reduction, 2) risks and benefits of a polypill in women compared to men, 3) anticipated hurdles to implementing a polypill strategy, 4) special considerations related to low- and middle-income country settings, and 5) potential sex-specific polypill strategies. Keywords Polypill . Women . Cardiovascular disease . Prevention Introduction Wald and Law [1] projected that a fixed-dose combination, or polypill, strategy could reduce incidence of cardiovas- cular disease (CVD) by > 80% based on a meta-analysis of observational and clinical trials data for aspirin, statins, blood pressure–lowering medications, and folic acid in the primary and secondary prevention of ischemic heart disease and stroke. Several authors independently proposed the broad concept of a prevention polypill, composed of a combination of risk-reducing medications (aspirin and generic drugs to reduce cholesterol and blood pressure) [2, 3], but Wald and Law’s[1] explicit synthesis of the benefits from a fixed-dose combination (which they termed the “polypill”) generated much debate and discussion. Some have argued that Wald and Law underestimated the side effects (primarily associated with combining three antihypertensive therapies) and overestimated the benefits of this combination therapy strategy. In particular, less emphasis was placed on aspirin’s limited efficacy for primary CVD prevention in women. Also, there is concern regarding the appropriateness of using a single, standard medical intervention for heterogeneous global populations at risk for cardiovascular disease [4]. Others have noted that deriving conclusions from the combination of clinical trial and observational study data was not appropriate, citing the lack of efficacy of folic acid to reduce vascular events as a M. D. Huffman (*) Departments of Preventive Medicine and Medicine (Cardiology), Northwestern University Feinberg School of Medicine, 680 North Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA e-mail: m-huffman@northwestern.edu M. K. Ali Hubert Department of Global Health, Emory University Rollins School of Public Health, 1518 Clifton Road NE, Room 7051, Atlanta, GA 30322, USA e-mail: mkali@emory.edu K. M. Venkat Narayan Hubert Department of Global Health, Emory University Rollins School of Public Health, 1518 Clifton Road NE, Room 7030, Atlanta, GA 30322, USA e-mail: knaraya@emory.edu Curr Cardiovasc Risk Rep (2011) 5:280–286 DOI 10.1007/s12170-011-0161-9