The Polypill Revisited: Why We Still Need Population-Based Approaches in the Precision Medicine Era

Nearly 2 decades ago, Wald and Law proposed “a strategy to reduce cardiovascular disease by more than 80%” by administering a polypill to everyone 55 years of age and older. Their bold proposal had its roots in the debate surrounding risk-based versus population-based approaches to prevention, as described by Rose. In risk-based approaches, preventive measures are targeted specifically at higher risk individuals, with medication therapy tailored to each patient’s risk factor profile. The identification of higher risk patients typically relies on clinical and laboratory-based prediction algorithms, the traditional approach endorsed in most practice guidelines. In contrast, population-based approaches aim to shift the entire risk distribution, even modestly, with measures implemented at the population level. The latter necessitates interventions that are low in cost and have a low incidence of side effects. These are among the proposed advantages of the polypill, a fixed-dose combination of cardiovascular medications, usually including a statin and several antihypertensive drugs.

One of the objections to the Wald and Law proposal was that large numbers of low-risk individuals would end up receiving unneeded and/or unindicated drug therapy. Thus, despite randomized trials supporting the tolerability of various polypill formulations and regulatory approval in multiple countries outside the United States, momentum in the field shifted toward viewing the polypill primarily as a strategy for high-risk individuals with established cardiovascular disease. The problem is that a one-size-fits-all approach to pharmacotherapy may not be optimal for patients with established disease, for whom aggressive cholesterol and blood pressure targets often require titration of multiple medications. Furthermore, secondary prevention patients often have comorbidities such as diabetes that influence the choice of therapy.

Thus, several decades since Wald and Law’s original proposal, there remains little clarity regarding the role of the polypill in cardiovascular care. This has coincided with the rising interest in precision medicine, a contemporary embodiment of the risk-based approach in the Rose framework. A natural question, then, is whether there is any place for a population-based strategy using the polypill in the present era with so much focus on precision medicine.

The full perspective article can be downloaded below.