A once daily polypill cuts the risk of major cardiovascular events such as heart attack, stroke, and heart failure by more than 20%, compared with lifestyle advice alone, finds the first large clinical trial* of its kind, published in The Lancet.
The findings show that the combination polypill — containing two commonly used blood pressure lowering drugs, a cholesterol-lowering medicine, and aspirin — is effective for both the primary and secondary prevention of cardiovascular disease in the general population, and that the pros of widespread use outweigh any cons.
The PolyIran study recruited 6838 people aged 50 to 75 from the Golestan Cohort — a study tracking the health of over 50,000 adults from Golestan, a province in Iran ─ between 2011 and 2013.
Around one in 10 had a history of cardiovascular disease (CVD) (737 participants), and over three-quarters of these (588) were taking other cardiovascular drugs at the start of the study .
Villagers were either randomly assigned to lifestyle advice (116 villages; 3417 participants) or a once-daily polypill plus lifestyle advice (120 villages; 3421). Participants’ heart health was tracked over the next five years. Around 63% of those taking the polypill took it as recommended at least 70% of the time.
Compared with lifestyle advice, taking the polypill cut the risk of major cardiovascular events by 34%, overall — and by around 40% in those without a history of CVD over five years (136/3,033;4.5% vs 229/3068;7.5%), and by around 20% in those with previous CVD (66/388;17%) vs 72/349; 21%).
The effects were similar in both sexes and across the age bands. After adjusting for participants taking other cardiovascular drugs, the overall protective effect of the polypill fell to 22% from 34%, but remained statistically significant.
Systolic and diastolic blood pressure didn’t differ significantly between the groups, but LDL cholesterol was significantly lower among those taking the polypill.
The findings suggest that 35 people would need to take the polypill to prevent one serious cardiovascular event. In participants who took the polypill as directed at least 70% of the time, the number needed to treat would be 21. The polypill wasn’t associated with a significant reduction in the overall risk of death.
Crucially, the strongest protective effect was seen among participants who took the polypill as directed at least 70% of the time. Their risk was cut by more than half (57%) compared with those given lifestyle advice alone (86/2,144 ;4% vs 301/3417; 9%). But there was no corresponding improvement in blood pressure.
“Because the risks of side-effects from the components are very low, and the potential benefits are very high, the polypill is very safe. But the polypill is not an alternative to a healthy lifestyle and should be combined with physical activity, a healthy diet, and smoking cessation,” cautions lead study author Professor Reza Malekzadeh from Tehran University of Medical Sciences.
“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,” says co-author Professor Tom Marshall from University of Birmingham. “Because they have most to gain, the most efficient strategy would be to offer the polypill to those at highest risk of heart disease.”
Overall, the polypill was well tolerated and the incidence of side effects was similar between the groups. In total, 13% (440/3,421) of participants discontinued the polypill during the monitoring period — 60% of them (267/440) for reasons related to the treatment.
“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,” says co-author Dr Nizal Sarrafzadegan, Isfahan University of Medical Sciences, Iran.
Commenting on the findings, Professor Kausik Ray, chair in public health, Imperial College London, said: “Overall, this study reinforces the health benefits of even small reductions in blood pressure and cholesterol. However, I do not agree that aspirin should be used in the polypill. Instead, perhaps a more potent once-daily, long-acting blood pressure-lowering agent could provide more benefit to patients.”
Professor Jeremy Pearson, associate medical director at the British Heart Foundation, added: “The findings are not transferable to high-income countries where baseline preventive medical care to reduce heart and circulatory disease risk is common.
“In the UK, as many as a third of people with high blood pressure are undiagnosed and many of those who are diagnosed aren’t managing their condition properly, even though we already have several effective medicines.
“This means that the biggest priority in the UK is to identify more people who do not realise they have high blood cholesterol or high blood pressure, and to help people prescribed medications to take them as prescribed.”
Gholamreza R, Khoshnia M, Poustchi H, et al. Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial.