A new perspective challenges recent restrictions on aspirin for preventing heart attacks and strokes in healthy people, arguing that major guidelines may be based on flawed interpretations of a key trial.
Experts say stopping aspirin use based solely on age could be harmful and emphasize individualized decisions made by doctors who understand each patient’s risks and benefits. They also stress the importance of not abandoning a potentially life-saving, affordable option in the broader fight against cardiovascular disease.
Shifting Guidelines on Aspirin Use
Recent medical guidelines have scaled back the use of aspirin for preventing first-time heart attacks and strokes. The American Heart Association (AHA) and the American College of Cardiology (ACC) recommend limiting aspirin use to people under 70. More recently, the U.S. Preventive Services Task Force (USPSTF) lowered that age limit to 60. But since the risk of heart attacks and strokes increases with age, these changes have left many healthcare providers uncertain: when should aspirin be stopped, who should still take it, and does age alone tell the whole story?
Researchers Challenge Current Recommendations
In response, researchers from Florida Atlantic University’s Schmidt College of Medicine, along with prominent collaborators who have led major aspirin trials, have published a new perspective in Clinical Trials, the journal of the Society for Clinical Trials. In their article, titled “Aspirin in Primary Prevention: Undue Reliance on an Uninformative Trial Led to Misinformed Clinical Guidelines,” they argue that key decisions about aspirin may have been based on a misreading of the evidence.
Misinterpretation of the ASPREE Trial
The authors emphasize that best practices for the design, conduct, analysis and interpretation of randomized controlled trials should adhere to rigorous statistical principles. Failure to follow these principles can lead to conclusions inconsistent with the totality of evidence and inappropriate recommendations made by guideline committees. They believe that both the AHA/ACC Task Force and the U.S. Preventive Services Task Force were unduly influenced by the uninformative, not null, results of the Aspirin in Reducing Events in the Elderly (ASPREE) trial. Specifically, this trial did not provide reliable evidence that aspirin showed no benefit in the age groups they enrolled.
Individualized Risk Assessment is Key
“The reliable evidence indicates 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 judgments about prescribing aspirin on a case-by-case basis and based on benefit-to-risk not just age alone,” said Charles H. Hennekens, M.D., FACPM, co-author and the first Sir Richard Doll Professor of Medicine and Preventive Medicine, Schmidt College of Medicine. “Further, it seems counterintuitive among patients taking aspirin long term to stop it just because a birth milestone is reached. Finally, absence of evidence does not equate to evidence of absence of effect.”
The authors stress that patients should consult their primary care provider about whether they are candidates for aspirin, as providers have the most knowledge of all the benefits and risks for each of their individual patients. In brief, health providers are equipped to balance the benefits to each patient of clot prevention against their individual bleeding risks. Thus, whether to prescribe aspirin should be an individual clinical judgment.
Aspirin’s Role in Acute Cardiac Events
“Healthcare 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 Hennekens. “In addition, health care providers and patients should remain cognizant that among survivors of prior heart attacks or occlusive strokes, aspirin should be prescribed long-term unless there is a specific contraindication.”
The authors highlight the growing burden of cardiovascular disease, stressing the need for broader lifestyle changes and effective as well as affordable drug therapies for primary prevention. These changes include quitting smoking, weight loss, increased physical activity, and using statins and other medications to manage blood pressure. With respect to costs, aspirin is a particularly attractive option.
Patient Preference and Risk Tolerance Matter
“While patient preference is always important to consider in decision-making, this assumes even greater relevance among patients in whom the absolute benefits and risks of aspirin are similar,” said Hennekens. “Patient preference may include consideration of whether the prevention of a first heart attack or stroke is a more important consideration to them than their risk of a significant gastrointestinal bleed.”
The authors also note that the absolute risk of a cerebral bleed without, as well as with aspirin, is too low to be of clinical relevance for the vast majority of patients. In the U.S. and most developed countries, the authors say that individual clinical judgments by healthcare providers about prescribing aspirin in primary prevention may affect a relatively large proportion of their patients. For example, metabolic syndrome, a constellation of overweight and obesity, hypertension, high cholesterol ,and insulin resistance, a precursor to diabetes mellitus, affects about 40% of Americans 40 years of age and older and is increasing globally. The high risks of patients with metabolic syndrome for a first heart attack and stroke may approach those of patients with a prior event.
The Need for Physician Judgment Over Blanket Guidelines
“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 knowledge about the overall benefits and risks for each patient and should make individual clinical decisions.”
According to the U.S. Centers for Disease Control and Prevention, 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.
Reference: “Aspirin in primary prevention: Undue reliance on an uninformative trial led to misinformed clinical guidelines” by Janet Wittes, David L DeMets, KyungMann Kim, Dennis G Maki, Marc A Pfeffer, J Michael Gaziano, Panagiota Kitsantas, Charles H Hennekens and Sarah K Wood, 1 April 2025, Clinical Trials.
DOI: 10.1177/17407745251324866
FAU collaborated with several distinguished academicians from the University of Wisconsin School of Medicine and Public Health, as well as the Harvard Medical School and Massachusetts General-Brigham Hospital.
Co-authors are Janet Wittes, Ph.D., an affiliate professor of biostatistics, FAU Department of Population Health; David L. DeMets, Ph.D., the first Max Halperin Professor and Chair Emeritus of Biostatistics and Informatics; KyungMann Kim, Ph.D., a professor of biostatistics and informatics; and Dennis G. Maki, M.D., FACP, all with the University of Wisconsin School of Medicine and Public Health; J. Michael Gaziano, M.D., a professor of medicine; Marc A. Pfeffer, M.D., Ph.D., FACC, Distinguished Dzau Professor of Medicine; and Sarah K. Wood, M.D., director of the Harvard Macy Institute, all at the Harvard Medical School, with Gaziano and Pfeffer also affiliated with Massachusetts General-Brigham Hospital; and Panagiota Kitsantas, Ph.D., professor of biostatistics and epidemiology and chair of the Department of Health Administration and Policy, George Mason College of Public Health.
Hennekens was the first to discover that aspirin prevents a first heart attack in men in the U.S. Physician’s Health Study and prevents a first stroke in women in the Women’s Health Study. He was the U.S. principal investigator on the worldwide Second International Study of Infarct Survival (ISIS02), which demonstrated the lifesaving benefits of aspirin when given within 24 hours of onset of symptoms of a heart attack as well as among long-term survivors of prior occlusive events affecting their heart, brain or peripheral arteries. 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 in the peer reviewed literature.
