Getting to the heart of the polypill

The polypill is being preferred for its efficacy in preventing secondary adverse cardiovascular events in people who have previously had a heart attack, but does the single pill pack a punch? Dr C Raghu finds out

Often it is not uncommon for patients to wish that their list of medications be pruned by the doctor on their next visit to the clinic. But they are often left bewildered to see additional medicines in the new prescription. Every few months new medicines with additional benefits are introduced to 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 as Wald and Law coined the term Polypill in 2003 to denote a fixed-dose medication combination for preventing cardiovascular disease. They suggested that administering a polypill to all adults above age 55 years would reduce cardiovascular events by more than 80%. This concept was not accepted by cardiologists despite recommendations from the World Health Organisation. The concept of polypill is useful for the treatment of lifestyle diseases, heart attacks, and brain stroke, where a synergistic effect of multiple medicines is required. Polypill contains smaller doses of multiple medicines reducing the side effects. Apart from reducing the pill burden and improving drug compliance, it translates into cost benefits. This led to a rapid acceptance of a fixed-dose polypill concept in 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 generic”. 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 whereas Indian doctors practised it for the past two decades. The concept of disease prevention can be broadly categorised as primary prevention or measures taken to prevent the onset of the disease in vulnerable people. For example, people with diabetes or hypertension have a high probability of developing their first heart attack. Measures taken to prevent the first heart attack are termed primary prevention. Secondary prevention indicates the steps taken to prevent the recurrence of a heart attack in those with a previous heart problem.

For the primary prevention of heart disease, a 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 the primary prevention of heart attacks even in a high-risk population discouraging aspirin as a component of a 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 from individual medicines leading to the stopping of polypills. 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 a polypill would be an ideal solution here. The only limitation would be a risk of under medication, owing to the inability to adjust the dosage of the individual components of the 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 is — 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 need to be flexible with the availability of the polypill in multiple strengths. Fortunately, India has a wide choice of polypills for lifestyle diseases. Polypills are being widely used in low socio-economic countries as they were economical. Two recent Polypill trials — PolyIran and SECURE that studied polypill in primary and secondary prevention respectively, demonstrated superior outcomes.

(The author is a Hyderabad-based cardiologist.)