International Polycap Study 3 (TIPS-3) Finds Polypill With or Without Aspirin Reduces Cardiovascular Risk

International Polycap Study 3 (TIPS-3) Finds Polypill with or without Aspirin Reduces Cardiovascular Risk

Sponsored by Canada’s Population Health Research Institute, an international study of people with no previous heart disease or stroke, however at intermediate risk, discovered that Polypill along with aspirin cuts heart attacks and strokes by up to 40%. That heart attacks, strokes and other cardiovascular incidents can be cut by 20 to 40 percent through use of polypill, which combines three blood pressure medications and a lipid lowering medication taken alone or with aspirin is the notable findings of the study, led by Salim Yusuf, co-principal investigator and professor of medicine at McMaster University, along with the International Polycap Study 3 Investigators. The findings were recently published in the prestigious New England Medical Journal

TrialSite News provides a brief breakdown for the network.

What problem is this therapy approach addressing?

The cardiovascular disease crisis. Presently, this represents the world’s most common illness with about 18 million deaths annually; over 80 percent of these occur in low-income and middle-income countries. Moreover, according to the recent press release issued by McMaster University in Canada, over 40 million people worldwide are impacted by cardiovascular events annually if including those individuals who have recovered from a heart attack or stroke.

What was the Polypill used in this study?

The formulation of various polypills can vary however for purposes of the TIPS-3 study the preventive therapy included 40 mg simvastatin; 100 mg of atenolol; and 25 mg of hydrochlorothiazide, and 10 mg of ramipril. This cocktail can be combined with 75 mg of aspirin per day.

What are the study details?

The study (NCT01646437) was a randomized 2x2x2 factorial design placebo controlled trial targeting 5,714 participants (women 55 years or older and men 50 years or older) without known heart disease or prior stroke and without a clear indication or contraindication to any of the study medications. Eligible and consenting individuals were randomized to receive either the study drug or placebo (dummy pills) and were monitored for an average of five years. 

The study included subjects from 9 countries and was led by an international group of investigators (scientists and physicians) with coordination managed by the Population Health Research Institute at Hamilton Health Sciences. Study participants and sites ranged from Bangladesh and India to Philippines, Tanzania and Canada however the majority of participants resided in India and the Philippines.

This study started back in 2012 and the estimated primary completion date was just in June 2020.

Who was the Study sponsor(s)?

Led by Dr. Salim Yusuf, the study’s primary sponsor is the Population Health Research Institute founded by Salim Yusuf in 1999 to broaden research agenda based on a preventive cardiology and therapeutic program first launched in Hamilton Canada in 1993. Since then, this research institute has established an extensive network worldwide of collaborators in 102 countries participating in a wide range of types of large clinical trials, studies and registries.

Collaborators offering funding and support include Cadila Pharmaceuticals, (one of the India’s largest pharmaceutical companies emphasizing economical therapies), Wellcome Trust (a charitable organization with funded by £26.8 billion investment portfolio), Canadian Institutes of Health Research (CIHR) (federal agency responsible for funding health and medical research in Canada) and the Heart and Stroke Foundation of Ontario (a non profit).

The Results

The data generated by TIPS-3 is based on the ongoing monitoring of the study participants for an average of 4.6 years. With the results published in the NEJM, co-principal investigators are scheduled to present the results of this breaking study at the 2020 American Heart Association scientific sessions. Lead study co-principal investigator and professor of medicine at McMaster University Salim Yusif declared the results of TIPS-3, “…is the start of a transformational approach to preventing heart disease. We could save millions of people from experiencing serious heart disease or stroke each year with effective use of the polypill and aspirin.”

Again heart attacks, strokes, and other cardiovascular incidents can be cut by 20 to 40 percent through the use of the polypill, containing blood pressure medications and a lipid lowering medication taken alone or with aspirin. More specifically those individuals with no previous heart disease or stroke, but at intermediate risk, found the polypill alone may reduce the risk of heart attack, stroke, revascularization procedures (such as angioplasty or heart surgery) or other cardiovascular incidents by about 20 percent, and the combination of the polypill and aspirin can reduce those same cardiovascular events by up to 40 percent.

Overall, the study found only 4.4 per cent of those who took the polypill alone had a heart attack, stroke, revascularization procedure or died of cardiovascular problems compared to 5.5 percent who took the placebo. Of those who took just the aspirin the incidence was 4.1 per cent compared to 4.7 per cent of those with the placebo.

Co-principal investigator Prem Pais, from St. John’s Research Institute informed, “The results of the study have implications for reducing the burden of cardiovascular diseases globally. Even if only one third of eligible people receive a polypill, its use will likely avoid millions of individuals experiencing serious cardiovascular diseases worldwide.” Dr. Pais continued on these important findings, “It also opens the way for a community-based approach with health workers working under a physician’s supervision, enabling the pill to reach a large number of people.”

A second author of the study, Philip Joseph reminded that this approach can certainly benefit individuals in rich and poor countries based on current gaps in care worldwide.  

Lead Research/Investigator

Salim Yusuf, MD, BS, D.Phil, FRCP (UK), FRCP (C), FACC, Professor, McMaster University, Executive Director, Population Health Research Institute

Prem Pais, MBBS, St. John’s Research Institute

Philip Joseph, associate professor of medicine, McMaster University, Investigator at PHRI, Cardiologist at Hamilton Health Sciences

Call to Action: Check out the results in NEJM. Note that Dr. Yusuf share that advancements in polypills forthcoming will likely be even more effective.