Polypill and aspirin together make a difference in large-scale results testing

Aspirin has added to the benefits of a low-cost polypill approach for primary prevention of cardiovascular disease (CVD) in medium-risk populations. TIPS-3 study Found.

People who received polypills in the study were in the placebo group (4.4% vs 5.5%, HR 0.79, 95% CI 0.63-1.00).

Considering many issues related to conducting the study, such as reduced medication adherence due to delayed drug supply, researchers performed sensitivity analysis to count CVD events within 30 days of those who discontinued the drug for non-medical reasons However, it improved slightly (HR 0.74, 95% CI 0.57-0.97).

The 5,713 study was presented at this year’s Virtual American Heart Association (AHA) conference by Dr. Salim Yusuf of the Institute for Population Research and Health at McMaster University in Hamilton, Ontario.The complete manuscript was published at the same time New England Journal of Medicine..

TIPS-3 participants who received only aspirin had a poorer total rate of cardiovascular death, MI, or stroke compared to placebo (HR 0.86, 95% CI 0.67-1.10). This finding has not changed after sensitivity analysis (HR 0.83, 95% CI 0.62-1.10).

Nevertheless, the addition of aspirin to polypills further reduced the CVD risk compared to double placebo (4.1% vs. 5.8%, HR 0.69, 95% CI 0.50-0.97). The results after the sensitivity test looked even better (HR 0.61, 95% CI 0.41-0.91).

“We hope this is the best evidence that aspirin is more beneficial than other treatments,” Yusuf said at an AHA press conference. “Carefully selected aspirin plays a role in primary prevention, along with lifestyle management and the use of the remaining polypill ingredients.”

Especially, Aspirin was downgraded In 2019 AHA and American College of Cardiology CVD Primary Prevention Guidelines There was no net benefit to the elderly and diabetics after the ASCEND and ARRIVE trials, according to Donaldroid Jones, MD, MD, Moderator and AHA Chairman of the Northwestern University School of Medicine in Chicago.

Benefits of Aspirin CVD Rise and arrive Yusuf suggested that TIPS-3 was offset by lower bleeding rates, probably due to the break-in period and low aspirin dose (75 mg daily).

Overall, the benefits of fixed-dose combination therapy are consistent throughout the study, including: HOPE-3 And Poly IranAccording to session debaters Anushkapatel, MBBS, SM and PhD at the George Global Health Institute in Sydney, Australia.

TIPS-3 was implemented primarily in middle-income countries, but she commented that it is globally relevant.

“Today, there is a paradigm shift in front of us,” Lloyd Jones said, agreeing that the polypill approach is applicable to environments around the world, but argued that it was particularly attractive. Low resource settings..

Yusuf emphasized that the polypill approach can benefit both rich and poor countries. “Why don’t wealthy people benefit from something that is easy to consume and can reduce risk by 30-40%?” He said, “This is for the poor.” He insisted that there was no basis for “myth” and asked.

According to Yusuf, polypills may serve as background therapy for most people, and very high-risk people are candidates for additional treatment.

TIPS-3 included people without CVD with a CVD risk of more than 1.0% per year, according to the INTERHEART risk score.

7,534 investigators, including lifestyle counseling, have entered the break-in period. Eventually, 5,713 people were randomly randomized 1: 1 to polypills or placebo. Within each group, patients were divided into those who received aspirin and those who did not.

Most patients were enrolled in India and the Philippines. The average age was 64 years and more than half of the cohort were women. At baseline, 84% showed hypertension or systolic blood pressure (BP) above 140 mm Hg, and 37% showed diabetes or glucose above 126 mg / dL.

The average follow-up period for TIPS-3 was 4.6 years.

The polypills in this study included atenolol 100 mg, ramipril 10 mg, hydrochlorothiazide 25 mg, and simvastatin 40 mg. According to Yusuf, once-daily capsules were “cost-neutral,” which was 33 cents per day in India.

Systolic blood pressure decreased by an average of 5.8 mmHg with polypills. LDL cholesterol decreased by 19.0 mg / dL.

The 30-40% reduction in CVD risk with the polypill / aspirin combination was smaller than what the researchers initially hypothesized, Yusuf said, pointing out multiple challenges for studying behavior.

Recruitment took five years instead of two, and while there were regulatory challenges in India, the protocol was not approved in China, Brazil and Argentina.

Also, in the last 6-9 months of the trial, drug production delays, import / export barriers, and the COVID-19 pandemic increased non-compliance rates. Of the patients who discontinued the assigned regimen, 42.2% belonged to the polypill comparison group and 39.7% belonged to the aspirin comparison group.

According to Yusuf, discontinuation had little to do with the side effects of polypills or aspirin, given the “excellent” safety data that did not show an increase in bleeding rates over placebo.

Another reason for the lower than expected reduction in CVD risk may be related to the chemical stability of the polypill formulation used in TIPS-3. According to Yusuf, his group is testing capsules over the next few months.

“No major pharmaceutical company is funding this,” he lamented. “It was very difficult to fund and complete the research.”

“I encourage some Western companies to develop polypills. It doesn’t matter what the ingredients are, it will work,” said the test leader. He suggested that buying large amounts of polypills, as in the case of vaccines, would make sense for some large payers.