SECURE Polypill trial: New life for an old idea

By Dr. Oliver Jones, edited by Dr. Ahmed El-Medany

Key points:

  • A polypill containing aspirin, ramipril, and atorvastatin was effective in reducing a composite of death and major cardiovascular events in post-MI patients
  • The polypill outperformed usual ESC guideline-directed medical care – the presumed mechanism is increased adherence

Polypills have seen fluctuating support in the cardiology community over the modern era. As recently as 2019, the PolyIran trial showed a polypill containing aspirin, atorvastatin, and antihypertensives to be effective for primary and secondary prevention of major cardiovascular events in a lower-resource setting. Despite this, for the most part, combination medications have not been incorporated into guidelines.

At a hot line trial session at the European Society of Cardiology (ESC) Congress 2022, investigators presented the results of the SECURE trial, a phase 3, open-label, randomised controlled trial of a single polypill containing combination aspirin 100mg; ramipril 2.5mg, 5mg, or 10mg; and atorvastatin 20mg or 40mg versus separate pills as part of usual ESC guideline-directed care, at the discretion of the treating physician.

2,499 post type 1 myocardial infarction (MI) patients across 113 centres in seven European countries were randomised and followed-up over a median of three years. Mean age was 76 years, 31% were female, 78% had hypertension, 57% had diabetes, and 55% had a history of cigarette smoking.

Event rates were significantly lower in the treatment arm for the composite primary endpoint of cardiovascular death, nonfatal type 1 MI, ischaemic stroke, or urgent revascularisation, with contributions from all components – event adjudicators were unaware of trial-group assignments.

The composite outcome occurred in 9.5% of the treatment group, and 12.7% of the usual care group (hazard ratio 0.76, 95% confidence interval 0.6-0.96, p=0.02 for superiority). For the key secondary endpoint of cardiovascular death, nonfatal MI, or stroke, rates were 8.2% and 11.7% respectively (hazard ratio 0.7, 95 confidence interval 0.54-0.90, p=0.005 for superiority). The frequency of cardiovascular death was 3.9% in the polypill group and 5.8% in the control arm.

The discrepancy was mostly attributed to adherence, with the investigators presenting data showing higher satisfaction scores, and 8-11% more patients achieving high adherence in the polypill arm. “Pill-burden” for post-MI patients has long been recognised as an unfortunate side-effect of the ever-growing armamentarium of prognostic drugs available to physicians and patients. The associated effects on medication adherence are well-documented – adherence to secondary prevention medication is estimated to be approximately 50%.

Reception was broadly positive. In conversation with ESC TV, lead investigator Professor Valentin Fuster, described the results as “striking”, and compared the treatment effect (a 33% relative risk reduction in cardiovascular death), to the original trials introducing the component drugs found in the polypill. The investigators now plan to approach regulatory bodies to consider approval.

Read more:

SECURE trial in the New England Journal of Medicine:

PolyIran trial in The Lancet: