Physicians' Academy for Cardiovascular Education

Polypill plus aspirin lowers CV events in primary prevention setting

News - Nov. 23, 2020

A Polypill for Primary Prevention of Cardiovascular Disease in Intermediate Risk People: Results of the International Polycap Study (TIPS)-3

Aspirin Alone and in Combination With a Polypill in Cardiovascular Disease Primary Prevention: Results From the International Polycap Study (TIPS)-3

Presented during the AHA Scientific Sessions 2020 by Salim Yusuf, Hamilton, ON, Canada.

Introduction and methods

CVD is a huge global problem; 18 million deaths globally and ~40-50 million individuals experience MI or stroke each year. The majority of those experiencing CVD have no history of CVD, so primary prevention is key in reducing CVD in the community. Risk factors for CVD have a graded relationship with CV risk, so no threshold is present. And statins, betablockers, ACEi and aspirin together have shown to reduce CV risk by 75% in patients in secondary prevention setting. This risk reduction may be extended to a primary prevention setting.

The objectives were to examine whether a polypill reduced the composite of CVD events compared to placebo, whether aspirin reduced the composite of CV death, MI or stroke compared to placebo, and whether a polypill plus aspirin reduced the composite of CVD events compared to placebo. The composite of CVD events consisted of CV death, non-fatal stroke, non-fatal MI, heart failure, resuscitated cardiac arrest or arterial revascularization.

5700 Individuals were randomized to polypill or placebo and each group was further randomized to aspirin or placebo. The polypill consisted of atenolol 100 mg, ramipril 10 mg, HCTZ 25 mg and simvastatin 40 mg. Dose of aspirin was 75 mg daily. Inclusion criteria were ≥50 years for men and ≥55 years for women with an IHRS ≥10, or in those who were older (≥65 years) an IHRS of ≥5, resulting in population who had a CVD risk ~1.5%/year. Follow-up was 4.6 years.

Main results


In a population of intermediate CV risk with no history of CVD, use of the polypill reduced CVD by 21%, use of aspirin reduced CV death, MI or stroke by 14% and the combination of polypill and aspirin reduced the primary endpoint of CVD by 31% when compared to placebo. These results demonstrate that aspirin contributes importantly to the benefits observed.

In the end prof. Yusuf discussed the implications of the findings. First, if half of eligible individuals would use a polypill plus aspirin, 3 to 5 million CVD events could be avoided each year globally. Second, this is likely a cost effective strategy to meet global target of reducing CVD by 30% by 2030. Last, future polypills with more effective LDL-c and BP lowering may lead to greater benefits.


Anushka Patel said that now with results of the TIPS-3 trial, evidence from 3 large trials that evaluated a polypill-based strategy in >18.000 participants on important clinical outcomes is available. Although there are differences between these trials, the consistency of these trials (HOPE-3, TIPS-3 and PolyIran on CV outcomes (a 20-30% reduction in MACE) is clear, said Patel. The reduction in MACE was largely consistent with the observed reductions in BP and LDL-c.

Risk factor lowering was less than what might be expected based on number and doses of drugs involved (the effect of drugs was ~40% of what was expected). This is not explained by increased medication use in the placebo group, but somewhat explained by discontinuation in the study arms (reported study drug use at the end of the study was ~60%). Only small proportions of discontinuation was due to side effects and ~45% due to administrative barriers, leaving a substantial proportion due to other reasons related to health system, prescriber/patient preferences.

Whether aspirin should be included in a primary prevention polypill, TIPS-3 was not sufficient, according to Patel and the total evidence suggest a individualized approach.

The TIPS-3 was conducted largely in participants from middle-income countries, but the findings have global relevance, said Patel. Last year, a study examining a polypill in an underserved US population was published. With now evidence on clinical outcomes, it is difficult to argue against the value of a polypill approach in such a population and emphasizes the global relevance.

- Our reporting is based on the information during AHA Scientific Sessions 2020 -

The findings were simultaneously published in N Eng J Med Watch a video by prof. Yusuf

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