Participants without cardiovascular disease but who were at increased risk were randomly assigned to receive a polypill (i.e. 1 statin with 3 drugs to lower blood pressure) or placebo and to receive aspirin or placebo. With 4.6 years follow-up, the incidence of cardiovascular events was lower among participants receiving both the polypill and aspirin than among those receiving both placebos.
Prof. Salim Yusuf (Population Health Research Institute, Canada) presented the results of the TIPS-3 trial. TIPS-3 randomised 5,713 people, mostly of South Asian ancestry, who did not have cardiovascular disease but were classified as being at intermediate or high risk as measured by the INTERHEART Risk Score. The polypill contains 40 milligrams of simvastatin, 100 milligrams of atenolol, 25 milligrams of hydrochlorothiazide, and 10 milligrams of ramipril. One arm of the TIPS-3 trial tested the polypill versus placebo, another arm tested the polypill in combination with aspirin (75 mg daily) versus placebo, and a third arm tested just aspirin. The primary outcome of the trial was a composite score that included death from cardiovascular causes (stroke, heart attack) and heart failure, resuscitation from cardiac arrest, and revascularisation. The results were simultaneously published in the New England Journal of Medicine .
The mean follow-up was 4.6 years. Levels of low-density lipoprotein cholesterol level were lower by approximately 19 mg per decilitre and systolic blood pressure was lower by approximately 5.8 mmHg in the groups taking the polypill with or without aspirin when compared with placebo. The primary outcome showed a 21% difference in events in the polypill group (4.4%) versus the placebo group (5.5%; HR 0.79; 95% CI 0.63-1.00). Primary outcome events occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (HR 0.86; 95% CI 0.67-1.10).
The difference in the primary outcome was slightly better when aspirin was added, showing a 31% difference for the polypill + aspirin; events occurred in 59 participants (4.1%) in the combined-treatment group and 83 (5.8%) in the double-placebo group (HR 0.69; 95% CI 0.50-0.97).
All treatments had good safety profiles, although hypotension and dizziness were more common among those in the group taking the polypill and aspirin.
- Yusuf S, et al. Aspirin Alone and in Combination With a Polypill in Cardiovascular Disease Primary Prevention: Results From the International Polycap Study (TIPS)-3. LBS.02, Late-Breaking Clinical Science Virtual AHA Scientific Sessions 2020, 13-17 Nov.
- Yusuf S et al. Polypill with or without Aspirin in Persons without Cardiovascular Disease. New Engl J Med, Nov 13, 2020.DOI: 10.1056/NEJMoa2028220.