Polypill for prevention of heart attacks

On a rainy afternoon, Narayana visited Dr Venkatesh his personal Cardiologist who has been treating him for high blood pressure, elevated cholesterol and diabetes. Vigilantly he observed his prescription and asked “Can you cut off some medicines? It is bothersome to track the multiple medicines and timings”. Doctor replied “we have a new drug for diabetes that reduces heart attack which I added”.

It is not uncommon for patients to wish that the medication list be pruned at every visit. But they are bewildered to see additional medicines in the new prescription. Every few months new medicines with additional benefits are introduced into medical science leading to prescription elongation.

Polypill is one of the solutions for long prescriptions where multiple fixed-dose medicines for various diseases are combined in a single pill. This combination is to prevent future heart attacks. This concept is not new; Wald and Law coined the term Polypill in 2003 to denote a fixed-dose medication combination for preventing cardiovascular disease. They suggested administering a polypill to all adults above age 55years would reduce cardiovascular events by more than 80%. This concept was not accepted by the Cardiologists despite the World Health Organisation recommendations.

The concept of polypill is useful for treatment of life style diseases, heart attack, brain stroke, where synergistic effect of multiple medicines is required. Polypill contains smaller doses of multiple medicines reducing the side effects than when given at a higher doses. Apart from reducing pill burden and improving drug compliance, it translates into cost benefit. This led to rapid acceptance of a fixed-dose polypill concept in the lower socio-economic countries.

In the West, medicines are dispensed individually, and the concept of polypill was not encouraged as the fixed dose combination is rigid not accommodating dose adjustment. In addition, individual medicines are manufactured by different companies and there was no possibility of a polypill incorporating medicines from two manufacturers. But in India it is a common practice to see combination pills as most medicines are “branded generics”. Manufacturers combine different medicines within a single pill mainly to reduce the pill burden and improve medication compliance. The West was late to embrace the concept of polypill where as Indian doctors practised for the past two decades.

The concept of disease prevention can be broadly categorised as – Primary prevention – measures taken to prevent the onset of disease in vulnerable people. For example people with diabetes or hypertension have a high probability for developing their first heart attack. Measures taken to prevent first heart attack are termed primary prevention. Secondary prevention indicates the steps taken to prevent recurrence of heart attack in those with previous heart problem.

For the primary prevention of heart disease, standard polypill usually has a fixed-dose of Atorvastatin, Ramipril and Aspirin. But the role of these medicines is still under intense research. Recent trials showed that aspirin is not useful for primary prevention of heart attacks even in high risk population discouraging aspirin as a component of polypill for primary prevention. However, the PolyIran study showed a 30% reduction of events with polypill compared to individual medicines for primary prevention which contained aspirin. It is also not uncommon for patients to develop side-effects to individual medicines leading to stopping of polypill.

A combination of Aspirin, Ramipril, Beta blocker and statin is a standard secondary prevention polypill. Everyone with established cardiovascular disease requires life-long medical treatment and polypill would be an ideal solution here. The only limitation would be a risk of undermedication, owing to the inability to adjust dosage of the individual components of polypill. However, in the latest SECURE study published by Castellano and others in the New England Journal of Medicine, a fixed-dose polypill reduced repeat heart attacks in comparison with the same medicines given separately at similar doses.

So what has evolved over the past 20 years - polypill remains an attractive concept for both primary and secondary prevention of heart attacks. There is no single ideal polypill, instead the composition and dosage of individual components needs to be flexible with the availability of polypill in multiple strengths. Fortunately India has a wide choice of polypill for various life-style diseases. Polypill are being widely used in low socio economic countries as they were economical. Two recent Polypill trials - PolyIran and SECURE studied polypill in primary and secondary prevention respectively demonstrated superior outcomes.