Polypill Strategies in Secondary Prevention: Adherence Gains Against the Loss of Individual Titration

Abstract

The SECURE trial randomised 2,499 post-myocardial-infarction patients to a fixed-dose cardiovascular polypill (aspirin,
ramipril, and atorvastatin combined in one pill) or usual care, and found a 24% relative reduction in a composite of
cardiovascular death, myocardial infarction, stroke, or urgent revascularisation (hazard ratio 0.76), alongside a higher rate
of patient-reported adherence at both 6 months (70.6% vs 62.7%) and 2 years (74.1% vs 63.2%). A systematic review of 13
further studies confirmed the adherence benefit is not specific to one trial, replicating across five independent cohorts with
individual adherence gains ranging from roughly 10 to 35 percentage points. This adherence advantage has an
underappreciated cost, however: a fixed-dose polypill can only be titrated among the specific dose combinations the
manufacturer offers, not continuously to an individual patient's response. In SECURE itself, fewer than half of patients
(40.9%) ended up on the single most common combination, and the remaining majority required one of the trial's other pre-set
combinations -- meaning even a successful polypill strategy is, for most patients, already a compromise between the dose
flexibility of separate prescribing and the adherence convenience of one pill. This review sets out both halves of that trade-off
using the same trial and the same supporting literature.