Polypill plus aspirin reduces cardiovascular events

In an intermediate-risk population without cardiovascular disease (CVD), a polypill reduced CVD by 21% compared with placebo over 4.6 years, according to findings from the TIPS-3 study [1]. A combination of a polypill and aspirin yielded an even greater reduction of 31%.

The TIPS-3 study (NCT01646437) is a randomised controlled trial with a 2x2x2 factorial design, conducted in 9, mainly South Asian countries. Prof. Salim Yusuf (Population Health Research Institute, Canada) presented the results, which were simultaneously published in the New England Journal of Medicine [1,2]. TIPS-3 randomised 5,713 people who did not have CVD but were classified as being at intermediate or high risk as measured by the INTERHEART Risk Score. Mean age of the participants was 64 years, and 53% were female. The polypill contained atenolol (100 mg), ramipril (10 mg), hydrochlorothiazide (25 mg), and simvastatin (40 mg). In a 2-by-2-by-2 factorial design, 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 double placebo, and a third arm tested aspirin versus placebo. Each intervention included a control group that received a matching placebo. The primary outcome was a composite of death from cardiovascular causes and heart failure, resuscitation from cardiac arrest, or arterial revascularisation.

After a mean follow-up of 4.6 years, the primary outcome was reached by 4.4% in the polypill group (n=2,861) compared with 5.5% in its placebo group (n=2,852): a difference of 21% (HR 0.79; 95% CI 0.63–1.00; P=0.05). Adding aspirin to the polypill resulted in an even greater treatment benefit versus placebo: events occurred in 4.1% of the polypill + aspirin group (n=1,429) versus 5.8% in the matching double-placebo group (n=1,421): a difference of 31% (HR 0.69; 95% CI 0.50–0.97; P=0.03) (see Figure). A sensitivity analysis showed that this benefit was larger in those who were adherent to treatment (HR 0.61; 95% CI 0.41–0.91). The primary outcome occurred in 4.1% in the aspirin group (n=2,860) versus 4.7% in its placebo group (n=2,853): a difference of 14% (HR 0.86; 95% CI 0.67–1.10). All treatments had good safety profiles, although hypotension and dizziness were more common in the group taking the polypill and aspirin.

Figure: Polypill + aspirin versus double placebo — primary outcome. Modified from [2]


Reflecting on the clinical implications of the results, Prof. Yusuf highlighted the following:

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      1. A CVD risk reduction of 30-40% with polypill + aspirin is less than was originally hypothesised (likely due to multiple challenges the trial faced, including a high incidence of discontinuation due to reasons unrelated to side effects and site-restrictions due to the COVID-19 pandemic), but is nevertheless important.
      2. If half of eligible people used a polypill with aspirin, 3 to 5 million CVD events could be avoided worldwide each year.
      3. It is likely a cost-effective strategy to meet the global targets of reducing CVD by 30% by 2030.
      4. Future polypills that could reduce low-density lipoprotein cholesterol and blood pressure to a greater extent might lead to larger benefits.

 

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   1. 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, AHA Scientific Sessions 2020, 13–17 Nov.
   2. Yusuf S et al. New Engl J Med, Nov 13, 2020.DOI: 10.1056/NEJMoa2028220.

 



Posted on 17 February 202125 March 2024