Hamilton, ON (Aug. 29, 2021) – A combination therapy of aspirin, statins and at least two blood pressure medications given in fixed doses can slash the risk of fatal cardiovascular disease (CVD) by more than half, says an international study led by Hamilton researchers.
The fixed-dose combination (FDC) therapies were examined both with and without aspirin versus control groups in a combined analysis of more than 18,000 patients without prior CVD from three large clinical trials. FDCs including aspirin cut the risk of heart attacks by 53 per cent, stroke by 51 per cent, and deaths from cardiovascular causes by 49 per cent.
The results were welcomed by international leaders in cardiovascular research.
Approximately 19 million people worldwide die of CVD and twice as many experience heart attacks or strokes every year.
About 80 per cent of cardiovascular events occur in individuals without a prior history of such illness, meaning effective preventative strategies including medications in people without CVD is essential, if the majority of heart attacks, strokes and related deaths in the world are to be prevented, the authors of the study state.
“This combination, either given separately or combined as a polypill, substantially reduces fatal and non-fatal CVD events,” said lead author Philip Joseph, associate professor of medicine at McMaster University, investigator at the Population Health Research Institute and cardiologist at Hamilton Health Sciences.
“The largest effects are seen with treatments that include blood pressure lowering agents, a statin and aspirin together, which can reduce fatal and non-fatal cardiovascular events by about half.
“The benefits are consistent at different blood pressure levels, cholesterol levels and with or without diabetes, but larger benefits may occur in older people.”
Joseph is the first author of the meta-analysis study by the Population Health Research Institute (PHRI) of McMaster University and Hamilton Health Sciences. Salim Yusuf, executive director of the PHRI and Distinguished University Professor at McMaster, is the senior author and the Principal Investigator.
The study involved investigators from 13 countries and included participants from 26 countries and every inhabited continent of the world.
The study was published by The Lancet today and concurrently presented at the European Society of Cardiology Congress by Joseph.
FDC treatment strategies trialed by the researchers were previously thought to substantially reduce CVD events and are called ‘polypills’ when used in a single-tablet drug formula, but proof of the benefits has not been available until the last two years.
The concept of a combination pill was first proposed exactly 20 years ago as a strategy to substantially reduce CVD in the population and also in those who already have had a previous heart attack or stroke.
Early trials demonstrated improved patient adherence to treatment regimens and better risk factor control with a polypill, compared to the use of single drugs, usual care, or placebos.
“These results are huge, and its wide use can avoid between 5 and 10 million individuals experiencing a stroke, heart attack or dying from these conditions yearly,” said Yusuf.
“I could see a future with development of a stronger polypill where we could see a lowering of cardiovascular disease by 65 or 70 per cent around the world and leading to even greater benefits.
“Given that all the components of the polypill are generic and low cost, polypills can be provided to people at modest costs and are likely to be very cost effective.”
Researchers gleaned their findings from combining data from three big studies on a total of 18,000 people followed for about 5 years; and these included the International Polycap Study (TIPS)-3, the Heart Outcomes Prevention Evaluation (HOPE)-3 study and the PolyIran trial.
Other international experts and organizations praised the study results.
“The World Heart Federation (WHF) is committed to promoting cardiovascular health for everyone by reducing the CVD burden worldwide, in both developed and developing countries,” said WHF president Professor Fausto Pinto.
“The demonstration of a low-cost approach using fixed dose combinations to reduce CVD by about 50 per cent is extraordinary and represents a huge opportunity to tackle the condition globally, with a major potential impact on people's lives. The WHF has supported the use of a polypill for the last decade and these results provide robust evidence to strengthen our global advocacy strategy.”
Wellcome Trust Director Sir Jeremy Farrar said, “The Wellcome Trust supported one of the three major studies that are included in the analysis, based on the recommendations that emanated from a workshop convened with the World Health Organization in London in August 2001. The Wellcome Trust has been committed to evaluating low-cost widely applicable solutions for common diseases including cardiovascular disease. We are pleased that our support has contributed to the development of robust evidence indicating that the polypill or fixed dose combinations involving blood pressure lowering, statins and aspirin can reduce CVD substantially.”
The study was funded by the Population Health Research Institute.
About the Population Health Research Institute
The Population Health Research Institute is a Joint Institute of McMaster University and Hamilton Health Sciences. Its 350 researchers and expert staff coordinate large studies in 102 countries in all inhabited continents of the world and have included more than a million people. Discoveries by its scientists have contributed to better preventive and treatment strategies that are globally applicable. For more information, visit phri.ca.
Pictures of Salim Yusuf and Philip Joseph may be found at https://bit.ly/3mC5WRG.
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Fixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease: an individual participant data meta-analysis
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Declaration of interests SY reports grants from the Canadian Institutes of Health Research, Wellcome Trust, AstraZeneca, and Cadila Pharmaceuticals related to conducting the HOPE-3 or TIPS-3 studies. PJ, PG, EL, SIB, KT, and JB report institutional grants from the Wellcome Trust, Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Cadila Pharmaceuticals, and AstraZeneca related to the TIPS-3 or HOPE-3 studies (or both). RM and GR report institutional grant funding from Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou related to the PolyIran study. SY reports receiving honoraria and reimbursement for travel expenses from AstraZeneca, Bayer, Boehringer Ingelheim, and Ferrer. EL reports consulting fees from Amgen Canada, consulting fees and speaker honoraria from HLS Canada, institutional research grant from Boehringer Ingelheim, and consulting fees from NovoNordisk. MDH reports grants from the World Heart Federation via unrestricted educational grants from Boehringer Ingelheim and Novartis, grants from the American Heart Association, Verily, and AstraZeneca, and personal fees from the American Medical Association outside the submitted work. In addition, MDH has a patent pending for heart failure polypills. PP reports funding from St John’s Research Institute, Bangalore, India, during the conduct of the study. AR reports that George Health Enterprises, the social enterprise arm of The George Institute for Global Health, has received investment to develop fixed-dose combination products containing aspirin, statin, and blood pressure lowering drugs. George Health Enterprises has submitted patents for low-dose blood pressure combinations, on which AR is listed as one of the inventors. AR is seconded part-time to George Medicines. All staff employed by The George Institute have an institutional interest to declare with respect to George Health Enterprises, although none of the staff have a direct financial interest in these investments. DX reports grants from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Coca-Cola India, Eli Lilly, the Indian Council of Medical Research, Pfizer, Sanofi, UK Medical Research Council, and Wellcome Trust, outside the submitted work. JB reports personal fees from Bayer, outside the submitted work. RD reports grants from Amarin, DalCor, and the Population Health Research Institute, outside the submitted work. VF and JMC report grants from H2020 related to the ongoing SECURE trial. JMC reports receiving honoraria and reimbursement for travel expenses from Ferrer, Pfizer, and Bayer. AA reports grants from Bayer, EMS Pharma, and the Population Health Research Institute; and consulting fees from Bayer, Eli Lilly, NovoNordisk, and EMS Pharma outside the submitted work. All other authors declare no competing interests.