Cardiovascular disease (CVD) causes more mortality and morbidity than any other disease in both rich countries and poor countries [1]. The risk factors have been well-known for 50 years, but the optimal prevention strategy is still elusive. Primary prevention treats individuals before they have a heart attack, whereas secondary prevention focuses on individuals who have had a heart attack. Several classes of drugs treat cardiovascular risk factors, demonstrating benefits in both primary and secondary prevention [2]. Many of these drugs are off-patent, and therefore cheap. Six years ago, Wald and Law hypothesised that a “Polypill”, containing three anti-hypertensives, folic acid, simvastatin and aspirin, could reduce the rates of CVD by over 80%, if all adults over the age of 55 years took it [3]. This week the Lancet published the first ever trial of such a Polypill [4, 5]. The “Polycap” used in the study excluded folic acid, but included the other five agents. 400 individuals were randomly assigned the Polycap and 200 individuals were assigned to each of eight other treatment groups. At 12 weeks, the risk factor profile of participants was assessed. Using the changes in risk factor levels in the different arms of the trial, they estimated the reduction in CVD due to the Polycap. The Polycap could potentially reduce cardiovascular heart disease by 62% and stroke by 48% (compared with 88% and 80% in the Wald and Law model). Importantly, side-effects and discontinuation were no more likely with the Polycap than its constituent parts. The authors conclude that the Polycap cannot be assumed to be the “sum of its component parts” and longer trials are necessary. Cholesterol reductions were greater when simvastatin was used alone than in the Polycap, illustrating how drug interactions need to be identified. Cholesterol reductions were also greater in diabetics than non-diabetics, suggesting that it may have greater effects in high-risk populations than a “population-wide” approach. This trial is exciting for three reasons. Firstly, it shows the feasibility of combining agents in a single dose combination pill for CVD prevention. Secondly, it points to the benefit of multiple risk factor modification over treatment of risk factors in isolation. Thirdly, the Polycap is produced by an Indian generic pharmaceutical company and the trial was conducted across 50 centres in India. Clinical trials of treatments for CVD in developing countries have been lacking, compared with trials in infectious diseases. In this trial, the Polycap was tested in the population that may eventually gain the most benefit from it.

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1. Mortality by cause for eight regions of the world: Global Burden of Disease Study Lancet 1997; 349:1269-76. Murray CJ, Lopez AD.
2. Two decades of progress in preventing cardiovascular disease Lancet 2002; 360: 2–3. Yusuf S.
3. A strategy to reduce cardiovascular disease by more than 80% BMJ 2003. 326: 1419–1424. Wald NJ and Law MR.
4. Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial Lancet 2009. 10.1016/S0140-6736(09)60611-5 published online March 30. The Indian Polycap Study (TIPS).
5. Polypill 'could become a reality' BBC News