Professors Wald and Law claim that the Polypill - consisting of aspirin, ACE inhibitor, β-blocker, statin, diuretic, and folic acid - has the potential to prevent “more than 80% of cardiovascular disease”.1However, the Polypill approach has many shortcomings.
Data supporting the effects of a Polypill were from trials of single risk factor intervention, from which theoretical estimates for the additive effects of its individual components were extrapolated, and not from simultaneous intervention for several risk factors. The claims touted for the Polypill in a series of BMJ papers1,2 are therefore unlikely to translate into clinical practice.3
Evidence for the use of folic acid to decrease the risk of coronary disease is weak, and its inclusion in a Polypill is premature.
Drug safety is an important factor, and there is no direct empirical evidence of the side effect profile of a Polypill with six components but only the suggestion that 8-15% people would have side effects. Evaluating side effects becomes much harder with more components in a pill. Aspirin is associated with the highest risk of serious effects including gastrointestinal bleeding. β-blockers can also cause serious side effects, and research has shown no advantage of β-blockers in people without known ischaemic heart disease.
There is also the potential of drug-drug interactions if patients taking the Polypill are on other medications. Furthermore, Polypills are unlikely to be stable and formulating a Polypill with a good shelf life is likely to require time and money.Pharmaceutical cost of development and registration is unlikely to be cheap; and each additional component can cause an exponential increase in the work load required to prove safety and efficacy with resultant reductions in cost-effectiveness.
Many of the disadvantages of the Polypill may be overcome by the development of a Single-pill combination of a calcium-channel blocker and a statin, targeting the major cardiovascular risk factors: hypertension and dyslipidemia.Both calcium-channel blockers and statins have additional anti-atherosclerotic properties and numerous clinical trials have demonstrated their efficacy in reducing blood pressure, LDL-cholesterol, and cardiovascular events.4 Such a combination is likely to retain the safety and efficacy of its parent compounds and could, by varying dose levels, be used to target a wide variety of hypertensive patients with additional risk factors. And considering the fact that hypertensive patients with dyslipidemia represent a large proportion of those at risk for cardiovascular events,5 the preventive potential of a Single-pill becomes apparent.
1. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more
than 80%. BMJ 2003; 326:1419-24.
2. Rodgers A. A cure for cardiovascular disease? Combination treatment has
enormous potential, especially in developing countries. BMJ 2003;
3. Mayor S. Polypill will not change prevention of heart disease. BMJ 2004;
4. Blank R. A single-pill combination of amlodipine besylate and atorvastatin
calcium. Drugs Today 2006; 42:157-75.
5. Kannel WB. Blood pressure as a cardiovascular risk factor. JAMA