A cheap daily pill that combines four drugs cut the risk of heart attacks, strokes and heart failure in a large study, suggesting it could be a good way to help prevent heart problems especially in poor countries.
The pills contained two blood pressure drugs, a cholesterol medicine and aspirin. Many people can’t afford or don’t stick with taking so many medicines separately, so doctors think a polypill might help.
A previous study testing one in India found it lowered cholesterol and blood pressure.
The new study is much larger and gives stronger evidence because it tracked heart attacks, strokes and other problems—not just risk factors.
It involved about 6,800 people in Iran, ages 50-75, some with previous heart problems and others without them.
All got advice on healthy lifestyles and half also were given polypills.
After five years, 6% of those in the pill group had suffered a heart attack, stroke or heart failure versus 9% of the others.
That worked out to a 34% lower risk with the polypill, and a 22% lower risk after researchers took into account other heart drugs that participants were taking.
People who took the polypill most faithfully, at least 70% of the time, had even bigger reductions in heart risks.
The benefit mostly seemed to come from lowering cholesterol; blood pressure didn’t significantly change. Side effects were similar in both groups.
Some who developed a cough while on the polypill were switched to another version that substituted one of the four drugs. All of the drugs are cheap generic medicines now.
Results were published Thursday in the British journal Lancet. The study was paid for by Tehran University of Medical Sciences, a foundation and Alborz Darou, the company that makes the polypills.
“This is an important step in the right direction,” said Dr. Salim Yusuf of McMaster University in Canada, who leads another polypill study expected to finish next summer. “This could be used in every sensible country where we want to save lives.”
One study leader, Dr. Tom Marshall of Britain’s University of Birmingham, said the results show the polypill is a “viable strategy” to prevent heart disease in developing countries.
“It’s much simpler to give people one medication that manages a couple of risk factors at the same time,” he said.
Marshall said, however, that the benefits would be minimal for people who already have access to good health care.
“But if you’re in a system where people don’t have great access, then this is a significant advantage,” he said.
Dr. Amit Khera, director of preventive cardiology at Southwestern Medical School in Texas who had no role in the study, said he expected that polypills would start to be used more widely in the next few years if they’re shown to work in other groups besides the people of central Asian ancestry tested in the Lancet study.
“The biology is different in different populations, so before we apply it to all of India or all of North Africa, we need to know these polypills are actually safe in these populations,” he said.
More information: Gholamreza Roshandel et al. Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial, The Lancet (2019). DOI: 10.1016/S0140-6736(19)31791-X
Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide. Based on statistics from The World Health Organization (WHO), coronary heart disease (also known as ischaemic heart disease) and stroke are the top two causes of death globally .
Pharmacological therapy plays a key role in the secondary prevention of CVD. Large evidence supports drugs conferring mortality benefit from several different classes: antiplatelet agents, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), beta blockers and lipid-lowering drugs [2–4].
These are recommended by the WHO  and guideline bodies including the National Institute for Health and Care Excellence (NICE) [6,7], the European Society of Cariology (ECS) , the American College of Cardiology/American Heart Association (ACC/AHA)  and American Heart Association/American Stroke Association (AHA/ASA) .
In 2001, a fix-dose combination pill was proposed by the WHO and was specified as a combination of aspirin, beta-blocker, ACEI and statin. In 2003, Wald and Law proposed that a fixed-dose combination pill, called polypill, consisting of a statin, BP-lowering agents, aspirin and folic acid, could potentially reduce the risk of CVD by 80% in individuals from age 55.
Since the concept was presented, many research studies investigated the efficacy of different medication combinations. A recent systematic review and meta-analysis summarized 13 randomized controlled trials (RCTs) of different polypills with a total n = 9059, mainly conducted in individuals with pre-existing atherosclerotic cardiovascular disease.
The relatively short duration of follow-up meant that there were no definitive conclusions possible supporting mortality benefit of polypill from the RCT level evidence. . The current RCTs focused on comparison between polypill and usual care. There is still lack of RCT-level evidence on the effectiveness of individual drug combinations.
The existing evidence on individual drug combinations is from some previous observational studies, which have examined the impact of the combination of antiplatelet agents, ACEIs/ARBs, beta-blockers and lipid-modifiers, called evidence-based combination pharmacotherapy (EBCP) [13–17], but there has been no systematic review to synthesize these together.
Uncertainties surrounding EBCP that have not yet been systematically assessed include: (i) whether there is conclusive statistical evidence suggesting multi-drug treatments do better than single-drug treatments for mortality benefit (ii) whether increasing the number of components will confer additional benefits; and (iii) the role of each component of combination therapy, and whether certain combinations have more potent mortality lowering effects. This systematic review was conducted with a meta-analysis of existing observational studies that investigated the impact of the EBCP on mortality and cardiovascular events in the secondary prevention of CVD.