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Polypill cuts major cardiovascular events by a third, study finds

BMJ 2019; 366 doi: (Published 22 August 2019) Cite this as: BMJ 2019;366:l5268
  1. Stijntje Dijk,
  2. Pat Lok
  1. The BMJ

A once daily, low cost polypill combining four cardiovascular drugs reduced the risk of major cardiovascular events by a third over a five year period when compared with lifestyle advice, a large study has found.1

Poor adherence is particularly common among patients with cardiovascular disease, as previous studies suggest that around a third of patients stop taking their medicine as early as 90 days after a myocardial infarction.2

The concept of a polypill was first proposed over 15 years ago as a simple, cost saving approach to improve medicine adherence and reduce the burden of cardiovascular disease.3 But evidence of the long term effects of a polypill is lacking, particularly in primary prevention settings, and the polypill is still not widely used.45

For the study, published in the Lancet,1 researchers randomly assigned almost 7000 people in Iran aged 50-70 to receive lifestyle advice combined with a polypill (containing aspirin 81 mg, atorvastatin 20 mg, hydrochlorothiazide 12.5 mg, and either enalapril 5mg or valsartan 40mg) or lifestyle advice alone.

Results showed that the polypill reduced the risk of major cardiovascular events such as myocardial infarction, stroke, and heart failure when compared with lifestyle advice alone (202/3421 (6%) v 301/3417 (9%)) and indicated that the benefits of polypill use outweighed recorded adverse effects such as internal haemorrhage (0.3% of polypill treated participants), peptic ulcer (1.1%), and upper gastrointestinal bleeding (0.4%).

Participants showed high adherence to the polypill, as around 63% took it at least 70% of the time. Those who took the polypill as directed showed the biggest protective effect against future cardiovascular events, cutting their risk by over half (57%) when compared with those given lifestyle advice only. Systolic and diastolic blood pressure did not differ significantly between the groups, but low density lipoprotein (LDL) cholesterol was significantly lower in the polypill arm.

Reducing premature mortality

The findings suggest that 35 people would need to be treated with the polypill to prevent one person from having a serious cardiovascular event. In participants with high adherence to treatment the number needed to treat was 21.

Nizal Sarrafzadegan, coauthor from the University of Medical Sciences in Isfahan, Iran, said, “Given the polypill’s affordability, there is considerable potential to improve cardiovascular health and to prevent the world’s leading cause of death. Over three quarters of the 18 million people who die from cardiovascular diseases each year live in low and middle income countries, and a fixed dose polypill strategy, if adopted widely, could play a key part in achieving the bold UN target to reduce premature mortality due to cardiovascular disease by at least a third by 2030.”

The authors noted several limitations to their study, including that they used only two fixed dose combination pills and that different dosages of each drug or different combinations might change efficacy. They also acknowledged that the study was done in a rural population in Iran with a population largely of central Asian ethnicity, which might limit how the findings could be generalised to other countries.