A low-cost polypill that combines four cardiovascular drugs in a single pill can cut the risk of major cardiovascular events by a third over five years, according to a large five-year randomised trial.

The study involving almost 7,000 individuals aged 50–75 years in Iran found that the once-daily polypill safely reduces the risk of major cardiovascular events (CVD) such as heart attack, stroke, and heart failure compared with lifestyle advice alone.

The effects were seen in a wide range of individuals, including those with and without a history of CVD. This might substantially reduce the burden of cardiovascular disease if adopted widely, especially in low- and middle-income countries.

The findings, published in The Lancet demonstrate for the first time the effectiveness of a fixed-dose combination polypill—containing two commonly used blood pressure lowering drugs, a cholesterol-lowering medicine, and aspirin—for both the primary and secondary prevention of CVD in the general population, and indicate that the benefits of widespread polypill use outweigh any known side effects.

Crucially, participants who took the polypill as directed (at least 70% of the time) saw the strongest protective effect against future cardiovascular events—cutting their risk by more than half (57%) compared with those given lifestyle advice only (86/2,144 [4%] vs 301/3,417 [9%]). Nevertheless, the authors did not observe a corresponding improvement in blood pressure.

Study confirms the value of the polypill in CVD primary prevention

This study is the first to have a sufficient sample size and follow-up time to assess the effect of the polypill on long-term fatal and non-fatal cardiovascular events in primary prevention.

“The idea of the polypill has always been appealing, and now we know that a fixed-dose polypill can achieve clinical benefits in practice,” said Professor Reza Malekzadeh from Tehran University of Medical Sciences in Iran who led the research. “Because the risks of side-effects from the components are very low, and the potential benefits are very high, the polypill is very safe. In terms of risk reduction, we can see the people who benefit most are those with high adherence. But the polypill is not an alternative to a healthy lifestyle and should be combined with physical activity, a healthy diet, and smoking cessation.” 

“Polypills are commercially available in a number of countries for secondary prevention, but this is the largest trial confirming the value of the polypill and showing it is effective in primary prevention,” said co-author Professor Tom Marshall from University of Birmingham in the UK. “Because they have most to gain, the most efficient strategy would be to offer the polypill to those at highest risk of heart disease.” 

Poor medication adherence is particularly common among patients with cardiovascular disease, with research suggesting that around a third of patients stop taking their medication as early as 90 days after having a heart attack. The polypill concept was first proposed almost 20 years ago as a simpler, cost-saving approach to improve medication adherence and reduce the cardiovascular disease burden. But evidence of the long-term effects of the polypill is lacking, particularly in primary prevention settings, and the polypill is still not widely used.