Polypills for primary prevention of cardiovascular disease

Abstract

Polypills can contain multiple pharmaceutical agents targeting the cardiovascular system. The use of polypills in the secondary prevention of cardiovascular disease (CVD) has received broad support; however, the use of polypills in the primary prevention of CVD is more controversial. This controversy stems from an inherent resistance to the medicalization of primary prevention, and the lower CVD event rate in this population means that smaller absolute benefits are derived. Indeed, drug-related adverse effects, such as from aspirin, might even outweigh the benefits. The role of fixed-dose combination (FDC) therapy for blood pressure (BP) lowering in combatting the widespread undertreatment of high BP — the leading modifiable risk factor contributing to the global burden of CVD — has gained momentum. Increasing evidence suggests that FDC pills containing multiple low doses of BP-lowering drugs produce more effective BP lowering than the use of fewer separate BP-lowering drugs at higher doses, without an increase in adverse effects. Trials of FDC pills comprising three half-dose or four quarter-dose BP-lowering drugs have shown substantial efficacy. In this Review, we summarize the current evidence on low-dose BP-lowering FDC pills and the justification for this approach in the context of polypills in the primary prevention of CVD.The use of polypills containing multiple pharmaceutical agents targeting the cardiovascular system in the primary prevention of cardiovascular disease is controversial. In this Review, Chow and Meng discuss the barriers to the use of polypills and focus in detail on the use of fixed-dose combination pills containing low doses of multiple blood pressure-lowering drugs.Key pointsPolypills containing aspirin, a statin and blood pressure (BP)-lowering drugs have received strong support for the secondary prevention of cardiovascular disease\xa0(CVD).Polypills improve adherence to medication and decrease the levels of cardiovascular risk factors, including BP and blood lipids, in small studies with surrogate end points.Barriers to the implementation of polypills in the primary prevention of CVD include patient factors, clinician factors, the evidence base and regulatory and commercialization factors.Fixed-dose combination pills containing multiple BP-lowering drugs at low doses are more effective at lowering BP and have a better adverse event profile than individual drugs taken at full doses.Further evidence is needed on the effectiveness and tolerability of fixed, low-dose, triple-agent or quadruple-agent combination pills compared with usual-care strategies in various populations.