Several different drugs are available to treat many of the cardiac risk factors, so combining them in one pill could reduce heart disease by 80% globally. This approach has obvious appeal because heart disease is the leading cause of death worldwide. The Indian Polycap Study (TIPS), reported in The Lancet today, moves us one step closer to realising this dream.

TIPS is a large phase II randomised trial that assessed the effects of nine different pills containing either single agents or combinations of two, three, four, or five (the polypill) drugs, to measure their effect on risk factors such as blood pressure and cholesterol concentrations, as well as the feasibility and tolerability of administering a single pill to a relatively unselected group of patients.

The results from TIPS show that each of the components of the polypill did what was intended: the statin reduced cholesterol, the three antihypertensives reduced blood pressure, and aspirin reduced the clotting ability of the blood. They found one unexpected issue with the Polycap: the degree of cholesterol lowering was slightly less with the Polycap than in patients who got simvastatin alone. This effect seems to be related to the rate of conversion of simvastatin in the Polycap.

What are the challenges?

First, we need a large phase III trial with longer follow-up to assess the true feasibility of this strategy. How can the use of a polypill be implemented in a broad population?

Second, we would also like to have a large outcomes trial, to document a reduction in death, myocardial infarction, and stroke with the polypill approach compared with current practice.

Third, there is the issue of dose, which is a fascinating difference from current practice. The Polycap had just one dose (generally a moderate dose) of each agent. It might be feasible to consider having two or three broad strengths with some different doses of some components or there could be versions with only some components of the polypill.

A final challenge: would the availability of a single magic bullet for the prevention of heart disease lead people to abandon exercise and appropriate diet? Would this make two of the major root causes of heart disease worse? Hopefully not, but the medical profession would need to help ensure that this would not happen.

A final consideration is where would this polypill fit into current medical practice? The major appeal is its simplicity and low cost, which could improve compliance. Such appeal could have broad applicability in areas of the world with less access to medical treatment, where just one or two interactions with medical professionals could be the start of treatment that could lead to long-term cardiovascular prevention. But the polypill could also fit well into more modern medical systems, in which large proportions of patients with risk factors are untreated. If all these patients knew they could simply take their polypill, they might be more receptive to it—and as such vastly broaden the number of patients who might benefit from drugs that had been proven in multiple trials to reduce cardiovascular disease and mortality. Although TIPS does not provide all the answers, the study does take a first and crucial step forward and raises hope that, in conjunction with other global efforts to improve diet and exercise, the polypill could one day substantially reduce the burden of cardiovascular disease in the world.

Summarized from the original article in The Lancet, Volume 373, Issue 9672, Pages 1313 - 1314, 18 April 2009