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.

Key points

  • Polypills containing aspirin, a statin and blood pressure (BP)-lowering drugs have received strong support for the secondary prevention of cardiovascular disease (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.

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Fig. 1: Effectiveness of antihypertensive fixed-dose pills.

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Acknowledgements

C.K.C. is supported by a National Health and Medical Research Council of Australia Career Development Fellowship Level 2, co-funded by a Heart Foundation Future Leaders research fellowship. Comments on a draft of the manuscript and assistance with Fig. 1 were provided by A. Rodgers (The George Institute for Global Health, University of New South Wales and Westmead Applied Research Centre, University of Sydney, Australia).

Review criteria

The authors searched EMBASE, MEDLINE and the Cochrane Central Registry of Controlled Trials for relevant papers from inception of the database to August 2018. Selected papers were either randomized clinical trials of polypills containing a combination of LDL-cholesterol-lowering and blood pressure-lowering drugs and aspirin in primary prevention populations or randomized trials of fixed-dose combination drugs containing three or more low-dose blood pressure-lowering agents. The authors also identified studies from the reference lists of important clinical trials and published reviews. The papers were identified by Q.M. and supplemented by knowledge of the literature from C.K.C.

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Nature Reviews Cardiology thanks J. Castellano and other anonymous reviewer(s) for their contribution to the peer review of this work.

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Both authors researched data for the article, discussed its content, wrote the manuscript and revised and edited it before submission.

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Correspondence to Clara K. Chow.

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The authors declare no competing interests. George Health Enterprises, the social enterprise arm of the George Institute for Global Health, has received investment to develop polypills containing aspirin, a statin and blood pressure-lowering drugs.

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Chow, C.K., Meng, Q. Polypills for primary prevention of cardiovascular disease. Nat Rev Cardiol 16, 602–611 (2019). https://doi.org/10.1038/s41569-019-0209-y

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