This multicentre, 2-by-2-by-2 factorial study randomised 5713 participants with medium cardiovascular disease (CVD) risk to receive a polypill (containing a statin and three blood pressure medications) or placebo daily, aspirin 75 mg daily or placebo and vitamin D or placebo monthly. The study took place between 2012 and 2017 and participants were followed up for a mean period of 4.6 years. The planned follow up period of 5 years was reduced due to supply issues and the Covid-19 pandemic.
The primary outcomes measures of death from cardiovascular cause or CVD event (defined as myocardial infarction, stroke, arterial revascularization, cardiac arrest or heart failure) was found to be lower in the polypill plus aspirin (4.1%) arm compared to the double placebo group (5.8%) with a hazard ratio of 0.69; CI, 0.50 to 0.97. Discontinuation due to side effects was similar between the two groups. Whilst there was a higher incidence of hypotension dizziness and cough in the polypill plus aspirin group there was no excess in bleeding events when compared with the double placebo group. The initial run-in period however excluded some patients due to side effects along with anyone not achieving over 80% concordance with the study medication. For the comparison of aspirin to placebo there was trend toward lower risk of CVD events including CVD death, MI, and stroke (0.86, 95%CI 0.67-1-10) which is consistent with the expected reduction in risk based on previous studies.
In summary, in the intention to treat analysis there was a 31% reduction in CVD events in the polypill plus aspirin group when compared to the double placebo group.
The authors conclude:
‘Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk.’
For further information please see:
Yusuf S, Joseph P, Dans P et al. Polypill with or without Aspirin in Persons without Cardiovascular Disease. NEJM 2020, Nov, 13. DOI: 10.1056/NEJMoa2028220.