Last week, in a major policy change, the WHO included three fixed dose combinations of cardiovascular medicines or polypills on its revised Model Lists of Essential Medicines (EML) 2023 for use in primary and secondary prevention of atherosclerotic cardiovascular diseases.
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The WHO Expert Committee on Selection and Use of Essential Medicines noted the evidence from large randomised-controlled trials that the use of the polypill is associated with reduced risks of cardiovascular events, including fatal and non-fatal myocardial infarction and stroke, and the need for revascularisation in primary and secondary prevention settings.
Endorsement of effort
For Salim Yusuf, a cardiologist and researcher at McMaster University, Canada, and a Keralite, this endorsement from the WHO is the culmination of the two decades or more that he spent on building clinical evidence that polypills are a safe and effective strategy to reduce the future risk of heart attacks and strokes.
Dr. Yusuf and his co-researchers, N.J. Wald and M.R. Law, both from the U.K., had proposed in early 2000 that a polypill which combined two or more blood pressure lowering drugs plus a statin and aspirin could significantly reduce the risk of future heart attacks and strokes.
Since then, many other researchers — V. Fuster in Spain and Malekzadeh in Iran — have independently worked with different pharmaceutical companies to formulate different polypills and conduct large trials, involving over 25,000 people. They demonstrated that the polypill reduced the risk of future heart attacks and strokes by about 40% to 50%.
In fact, one of the polypills that has been included in the EML is Polycap (manufactured by Cadila in India). This four-drug combination (simvastatin + ramipril + atenolol + hydrochlorothiazide), along with acetylsalicylic acid or aspirin, is what Dr. Yusuf and his co-researchers from India had been studying since 2005.
“Our data from three versions of the Indian Polycap Study (TIPS) between 2005 and 2019 established the safety and efficacy of the polypill and that it reduces heart attack, strokes and deaths from heart attacks by 40%. This was despite the fact that 20% to 30% of the people stopped the medicine midway during the trial. The real effect is thus larger — may be about 60% reduction in future heart attacks — in those who consistently take the medicine.
Low-cost pill
The polypill is thus an important low-cost public health intervention which can prevent over millions of cardiovascular events and deaths every year,” says Dr. Yusuf.
It is a simple treatment that can be administered with very little monitoring to a majority of people, with backup from physicians. The polypill is not a new drug but a drug delivery mechanism, which improves medication adherence (because it is a single pill) and saves money by preventing hospitalisations.
It has, however, taken more international research as well as several applications before the WHO was willing to include the polypill in the EML.
“Though we had data about how the polypill improved medication adherence and lowered blood pressure and cholesterol, the WHO wanted data from multiple studies that the pill can reduce serious cardiac events like heart attacks and strokes and that it can also reduce the need for angioplasty or cardiac surgery. Understandably, the WHO was taking a cautious approach because their decisions apply to many countries,” Dr. Yusuf points out.
Despite the positive data and the availability of the polypill (Polycap) in India, the idea did not catch on in the country earlier. Dr. Yusuf thinks that this was because the clinical studies were all in the area of primary prevention and the cardiologists were not willing to go along with that.The data that the polypill actually reduced cardiac events was not available then.
Impressive results
But now that there are impressive results from various studies and the polypill has been endorsed by the WHO, there could be a sea of difference in the way cardiology clinicians practice.
Now that the polypill has made it to the EML, it is hoped that governments would purchase the drug and provide it through public hospitals at low or no cost.
“We hope that once the polypill becomes part of the government’s drug formulary, private practitioners will also start prescribing it. The change will be gradual but the results of the studies are too impressive to ignore. It is my feeling that there will be many polypills in the market soon and for people who are at high risk (elevated cholesterol levels and blood pressure and diabetes), the polypill can help prevent the first heart attack,” Dr. Yusuf says.
