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Researchers Urge: ‘Prescribe Aspirin Based on Benefit-to-Risk Not Age’

Aspirin, Heart Attack, Stroke, Prevention, Public Health, Older Adults, Health Care Providers, Benefit-to-risk, Cardiovascular Risk, Risk of Bleeding, Primary Care

Health care providers are understandably confused about whether or not to prescribe aspirin for primary prevention of heart attacks or strokes, and if so, to whom.


By gisele galoustian | 1/5/2022

Recent guidelines have restricted aspirin use in the primary prevention of cardiovascular disease to patients under 70, and more recent guidance to patients under 60. Yet, the risks of heart attacks and strokes increase markedly with age.

There has been considerable confusion from recently reported results of four large-scale randomized trials of aspirin in high-risk primary prevention subjects, two of which showed significant benefits of aspirin, but the other two, based possibly on poor adherence and follow-up, did not. As a result, health care providers are understandably confused about whether or not to prescribe aspirin for primary prevention of heart attacks or strokes, and if so, to whom.

Researchers from 91’s and collaborators provide guidance to primary care providers and their patients in their perspective, “Primary Care Providers Should Prescribe Aspirin to Prevent Cardiovascular Disease Based on Benefit to Risk not Age,” published online ahead of print in the journal .

The authors urge that to do the most good for the most patients in primary prevention of heart attacks and strokes, health care providers should make individual clinical judgements about prescribing aspirin on a case-by-case basis and based on benefit-to-risk not age. They conducted an updated meta-analysis, which adds the results of the four recent trials to the previous comprehensive meta-analysis of six earlier major trials, and aspirin produced a statistically significant 13 percent reduction in cardiovascular disease with similar benefits at older ages in each of the individual trials.

“Anyjudgments about prescribing long-term aspirin therapy for apparently healthy individuals should be based on individual clinical judgments between the health care provider and each of his or her patients that weighs the absolute benefit on clotting against the absolute risk of bleeding,”said , M.D., senior author and interim dean, 91 Schmidt College of Medicine. “For long-term use of aspirin or any over-the-counter drug, patients should consult their primary care provider.”

91 collaborated with leading clinical researchers from the and the , . The authors say that primary care providers have the most insight and knowledge to make appropriate recommendations in collaboration with their patients.

“Primary care providers also should be aware that all patients suffering from an acute heart attack should receive 325 milligrams of regular aspirin promptly, and daily thereafter, to reduce their death rate as well as subsequent risks of heart attacks and strokes,” said , M.D., Dr.P.H., co-author and the first Sir Richard Doll Professor and senior academic advisor, 91 Schmidt College of Medicine. “In addition, among long-term survivors of prior heart attacks or occlusive strokes, aspirin should be prescribed long-term unless there is a specific contraindication. In primary prevention, however, the balance of absolute benefits, which are lower than in secondary prevention patients, and risks of aspirin, which are the same as in secondary prevention, should be an individual clinical judgment.”

The authors emphasize that the increasing burden of cardiovascular disease in developed and developing countries underscores the need for more widespread therapeutic lifestyle changes as well as the adjunctive use of drug therapies of proven net benefit and affordable costs in the primary prevention of heart attacks and strokes. The therapeutic lifestyle changes should include avoidance or cessation of smoking, weight loss and increased daily physical activity, and the drugs should include statins for lipid modification, and multiple classes of drugs likely to be necessary to achieve control of high blood pressure.

“While patient preference is always important to decision making, when the absolute benefits and risks are similar, patient preferences assume increasing importance,” said , M.D., co-author and an assistant professor, 91 Schmidt College of Medicine. “This may include consideration of whether the prevention of a first heart attack or stroke is a more important consideration to a patient than their risk of a significant gastrointestinal bleed.”

The authors note that individual clinical judgements by health care providers about prescribing aspirin in primary prevention may affect a relatively large proportion of their primary prevention patients. For example, metabolic syndrome, a constellation of overweight and obesity, hypertension, high cholesterol, and , a precursor to diabetes mellitus, affects about 40 percent of Americans age 40 and older. Their high risks of a first heart attack and stroke may approach those of patients with a prior event.

“General guidelines for aspirin in primary prevention do not seem to be justified,” said Hennekens. “As is generally the case, the primary care provider has the most complete information about the benefits and risks for each of his or her patients.”

According to the United States , more than 859,000 Americans die of heart attacks or stroke every year, which account for more than 1 in 3 of all U.S. deaths. These common and serious diseases take a very large economic toll, costing $213.8 billion each year to the health care system and $137.4 billion in lost productivity from premature death alone.

Co-authors are , M.D., M.P.H., professor of medicine, and , M.D., Ph.D., Victor J. Dzau Professor of Medicine, both at Harvard Medical School and Brigham and Women’s Hospital; Bianca Biglione, a fourth-year 91 medical student; Alexander Gitin, an honors graduate of 91 and a third-year medical student at the University of Florida College of Medicine; professors , Ph.D., and , Ph.D., and Jean Bell McCabe, M.B.A., senior program manager, Department of Biostatistics and Informatics, University of Wisconsin School of Medicine and Public Health; and , Ph.D., the first Max Halperin Professor and chair emeritus of biostatistics and informatics at the University of Wisconsin School of Medicine and Public Health.

Hennekens was the first to discover that aspirin prevents a first heart attack in men and stroke in women and has lifesaving benefits when given during a heart attack as well as among long-term survivors’ prior events. Science Watch ranked him as the third most widely cited medical researcher in the world from 1995 to 2005, and five of the top 20 were his former trainees and/or fellows. Science Heroes also ranked Hennekens No. 81 in the history of the world for having saved more than 1.1 million lives. Gaziano was the principal investigator of the Aspirin to Reduce Risks of Initial Vascular Events (ARRIVE) trial, one of the four major trials recently reported.

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