Polypill-friend or foe?

Sir,

Cardiovascular disease (CVD) is the most common cause of death in developed countries and will continue to be so in coming years.[1] There is a close association between CVD, stroke, ischemic heart disease, renal failure, and a number of other modifiable risk factors.[1] Since cardiovascular mortality rates are rising in both industrialized nations as well as developing economies like India, there is an urgent need to develop new strategies to overcome this global burden. Newly diagnosed hypertensive patients are now usually prescribed more than one drug. Polypill is a fixed-dose combination of three or more cardiovascular drugs. The idea of polypill was coined by Wald and Law, and as expected, it triggered the debate among the scientists, researchers, and healthcare professionals.[2] It was proposed that a combination of drugs acting by distrait mechanisms would have a synergistic effect in order to increase the life expectancy.[2] Since combination of drugs from different classes cancel out each others′ untoward effects, their use as first-line therapy for the treatment of newly diagnosed hypertensive patients is gaining popularity.[3] Wald and Law[2] concluded that a combined pharmacological intervention should reduce ischemic heart disease events by 88% and strokes by 80% in persons at risk. After demonstrating the short-term safety and efficacy in reducing the risk levels, several multidrug formulations have been approved in India for the treatment of cardiovascular disorders [Table 1]. Fixed-dose combination therapy can offer potential advantages over individual drugs, including increased efficacy, reduced incidence of adverse effects, lower healthcare costs, and improved patient compliance through the use of a single dosage form administered once daily.[1] However, there are issues and challenges ahead for the polypill before it gets firmly established in a clinical setting. Some of them include long-term safety and tolerability, long-term efficacy in reducing risk factor levels and cardiovascular events, physician, patient, and societal acceptability, adherence, regulatory requirements, cost, and impact on lifestyle habits.[4] Although more and more combinations are coming out in the market after proving their effectiveness in randomized controlled trials and in large multicenter studies, it is obvious that availability of these polypills would not only create confusion among the practicing cardiologists, but it may also lead to medication errors. This is because of the fact that it is not possible to remember the compositions of all these polypills. It is also difficult to tailor the therapeutic regimen for an individual in terms of number of drugs and their doses. In case of polypill, one is supposed to take a single pill which is supposedly designed to “fit in all sizes.” The less number of drugs in a single pill (a statin, nicotinic acid, and aspirin) has been suggested (mini-polypill) for the treatment of combined hyperlipidemia.[5] So, many polypills and so called mini-polypills may create “clinical chaos” in the coming years if they are not dealt with properly. The polypill concept is more spoken and less researched by the medical community. Only time will tell if the polypill is a friend or foe. Till then, it is suggested that a focused postmarketing surveillance is required for the polypill formulations presently marketed in the country. These studies may be well beyond the regulatory requirements so as to establish the safety and efficacy of polypills in the long run.

Table 1

Polypill formulations approved by Central Drugs Standard Control Orgenigetion (CDSCO)