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Recent work by WHO and others has shown that non-optimal levels of blood pressure and cholesterol are leading causes of this CVD burden in the U.S., other industrialized countries and, increasingly, in developing countries as well. Blood pressure and cholesterol are continuously related to CVD risk at least down to a SBP of 115 mmHg and to a total cholesterol level of 135 mg/dl. There is a large and growing evidence base which demonstrates that individuals with preexisting cardiovascular disease benefit from lowering BP and LDL-cholesterol and from antiplatelet therapy largely irrespective of how elevated their risk factors are. A major question which emerges is: can the potential for the primary prevention of CVD be achieved with one pill containing aspirin, BP lowering and lipid lowering treatment for those who are at higher absolute risk considering the cumulative effects of several risk factors even though they fall short of established guideline levels for treating either BP or lipids? The percentage of the general population which has high overall absolute risk but do not have a BP or cholesterol level that is typically treated with medications is quite large. About 50% of the population that develops CVD comes from this group. Thus, the impact on CVD of a simple, effective intervention for this population would be substantial . At present, such individuals are rarely medically treated because physicians and guidelines still focus almost exclusively on individual risk factors rather than on cumulative risk. Current guidelines (JNC VII, ATP III, ADA) all advise lifestyle intervention for these patients even though lifestyle alone has never been examined in a study with mortality/morbidity CVD endpoints. In addition most intensive lifestyle approaches have limited or no reimbursements by third-party payers. It is important to document the benefits on risk level changes and cost-effectiveness of intensive lifestyle versus limited lifestyle with and without the “polypill”. Studies are ongoing that aim to provide initial evidence for a new paradigm which will add the treatment of cumulative risks to the current practice of treating individual risk factors as an accepted model for preventing CVD throughout the world. The net benefits of polypill, combining a public health approach with the standard medical treat-to-goal approach could be enormous. Yusuf S,The Indian Polycap Study (TIPS) Lancet 2009 374:781 Wald NJ, LawMR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003; 326: 14-19.