Daily polypills and aspirin reduce the risk of CVD, death

New data from the TIPS-3 trial show that adults at moderate CV risk who are assigned polypills and aspirin experience CV events or death compared to adults who are assigned double placebo for almost five years. The chance was 31% lower.

“The most important finding is that the combination of polypills and aspirin, including multiple hypotensive drugs and statins, reduced the risk of cardiovascular disease, stroke, or death in randomized individuals by 30%, up to 40%. The person who actually took the medicine, Salim Yusuf, MD, DPhil, FRCP, FACC, Marion W. Burke, chairman of cardiovascular disease, and director of the Institute for Population Health at McMaster University School of Medicine, told Helio.

The benefits of CV observed in the daily polypill and aspirin regimens were lower than those of the original hypothesis. However, the findings remain important to the primary prevention population, Youssef said at a press conference at the Virtual American Heart Association’s science session. He said that if half of the eligible adults were prescribed polypills containing aspirin, they could avoid as many as 5 million CV events worldwide.

“I should hurry to add, which is important for’rich’and poor countries,” Yusuf said.

Study design

Salim Yusuf |

Yusuf et al. Analyzed data from 5,713 non-CVD adults at baseline with elevated intercardiac risk scores. Researchers randomly assign participants, Polypill once a day Contains 40 mg simvastatin, 100 mg atenolol, 25 mg hydrochlorothiazide and 10 mg ramipril or placebo once daily; 75 mg aspirin or placebo; or monthly vitamin D or placebo. (Vitamin D was evaluated, but their results are not shown here.)

Comparing polypill alone and polypill with aspirin, the primary outcomes were CV death, MI, stroke, resuscitative cardiac arrest, HF or revascularization. In aspirin comparison, the main outcome was CV death, MI or stroke. The cohort was followed for 4.6 years.

Survey results were released at the same time The New England Journal of Medicine.

During the last 18 months of the study, Yusuf said treatment compliance was “significantly reduced” due to medication difficulties associated with participants and associated supply problems. COVID-19 Pandemic..

Benefits of Polypill alone

Researchers found that participants assigned polypill therapy and placebo had a 21% reduction in relative risk of CV events (HR = 0.79; 95% CI, 0.63-1), and the curve diverged 6 months after the start of treatment. Observed to do. Pre-specified sensitivity analysis explaining non-compliance for non-medical reasons showed that participants assigned polypill therapy were 26% less likely to experience a CV event within 30 days of discontinuing medication. (HR = 0.74; 95% CI, 0.57-0.97).

“After stopping medication, the number of events is the same, and within 30 days of stopping medication, there is a 26% risk reduction,” says Yusuf.

Researchers have found that polypill therapy has a moderate effect on risk factors for CV. The mean difference between the polypill group and the placebo group in reducing systolic blood pressure was 5.8 mm Hg (95% CI, 5.1-6.4). The mean difference between groups of LDL cholesterol was 19 mg / dL (95% CI, 17.3-20.8).

“Initially, blood pressure dropped by 10 mm Hg, but over time this diminished,” says Yusuf. “This cannot be explained by the decline in adherence over time. I think the body is accustomed to the effects of lowering blood pressure and there is a compensatory mechanism.”

The reduction in LDL is also important, but “it was only about half of what we expected,” Yusuf said.

Benefits of Polypill and Aspirin

Researchers observed a 14% relative risk reduction at HR 0.86 (95% CI, 0.67-1.1) for major outcomes of participants assigned aspirin alone (n = 2,860) and placebo (n = 2,853) Did. No excessive bleeding was observed with aspirin vs. placebo. This is believed to be due to the low dose of 75 mg of Yusuf.

“We expect this to be the best evidence ever that aspirin benefits in addition to other preventive strategies,” said Yusuf.

Participants assigned polypill and aspirin (n = 1,429) were 31% less likely to experience a primary event during follow-up than participants assigned double placebo (n = 1,421). The HR was 0.69 (95% CI, 0.5-0.97). The event curve diverged again in six months, Yusuf said.

In a sensitivity analysis adjusted for non-compliance with non-medical factors, researchers observed a 39% reduction in the risk of major outcomes for polypill plus aspirin therapy and double placebo (HR = 0.61; 95%). CI, 0.41-0.91).

“Each component of the pill contributes to the benefits of combination therapy,” he said.

“Consistency of effect” between trials

During the discussion following the TIPS-3 presentation Anushka Patel, MBBS, SM, doctorate, FRACP, Deputy Principal and Principal Scientist at the George Global Health Institute and a medical professor at the University of New South Wales, Sydney, TIPS-3 is a series of indications that polypill therapy significantly reduces the CV risk in the primary prevention population He said he would add evidence.

“TIPS-3 provides direct evidence from three randomized trials evaluating polypill-based strategies in more than 18,000 participants. The key is the clinical outcome,” Patel said. I mentioned at the press conference. “Although there were some important differences between these three studies, the consistency of their effectiveness in preventing major CV events is clear.”

Patel said the reduction in risk factors with polypills was lower than expected. Lowering of BP and LDL cholesterol was about 40% of what was expected with individual component drugs, assuming 100% adherence to treatment. However, polypills have been shown to be safe and can provide significant clinical and public health benefits, Patel said.

“If we can address implementation and compliance challenges at the system, prescribing and patient level, the impact of polypill-based strategies on public health can be enormous, especially if polypills are affordable.” Patel said. “This is where I believe future research should be prioritized.”

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