Aspirin, Remarkable for Preventing Heart Attacks, Is Not for Everyone

Although some live by the phrase, ‘An aspirin a day keeps the doctor away,’ the scale weighing aspirin’s benefits and risks has tipped for certain groups.

Illustration by The Epoch Times, Shutterstock

“For many years in the 1990s and even early 2000s, everyone thought it was healthy to take a mini-dose aspirin every day just to prevent heart attacks,” Dr. Robert Lufkin, an adjunct clinical professor at the University of Southern California Keck School of Medicine, told The Epoch Times.

At that time, several large studies had demonstrated aspirin’s protective effects. The findings gave rise to the popular saying, “An aspirin a day keeps the doctor away.” Many doctors went as far as encouraging patients to take it regularly to prevent heart disease.

Now, the scale weighing risks against benefits has tipped somewhat.

Not a Supplement

Three major clinical trials concluded that aspirin is not suitable for preventive use in people without known cardiovascular disease.

The research goes back to 2018. At that time, the protective effect of low-dose aspirin for people with a history of cardiovascular events was already well-established. However, researchers sought to determine whether long-term use of low-dose aspirin (about 100 milligrams per day) could also prevent the first occurrence of cardiovascular events—known as “primary” prevention.

The Aspirin to Reduce Risk of Initial Vascular Events (ARRIVE) trial, involving patients with cardiovascular risk factors, showed that aspirin did not significantly reduce the incidence of cardiovascular events but did increase the risk of gastrointestinal bleeding. The proportion of participants experiencing a first cardiovascular event was similar in both the aspirin and placebo groups, but the risk of gastrointestinal bleeding was 2.1 times higher in the aspirin group.

Illustration by The Epoch Times

The Aspirin in Reducing Events in the Elderly (ASPREE) trial, which included more than 19,000 older adults, found that aspirin did not improve survival rates but significantly increased the risk of major hemorrhage by 38 percent and elevated all-cause mortality by 14 percent.

A third trial, A Study of Cardiovascular Events in Diabetes (ASCEND), which included more than 15,000 diabetes patients without cardiovascular disease, concluded that “the absolute benefits were largely counterbalanced by the bleeding hazard.” Compared to the placebo group, aspirin reduced the risk of serious vascular events by 12 percent, although increasing the risk of major (nonfatal) bleeding by 29 percent.

“Most of these trials have not shown a clear benefit so that overall, there has been skepticism about the possibility of using aspirin in primary prevention,” Dr. Raffaele De Caterina, chair of cardiology at the University of Pisa and head of the cardiology division at Pisa University Hospital, told The Epoch Times.

Since 2019, the medical community has stopped recommending aspirin broadly for primary prevention of heart disease.

That same year, the American Heart Association updated its guidelines, emphasizing that people without a history of heart attack or stroke—except for certain high-risk groups, such as those with an elevated risk of vascular disease or those already with evidence of subclinical vascular disease—should not take low-dose aspirin daily without consulting their doctor.

The U.S. Preventive Services Task Force offered more detailed recommendations, advising against the use of low-dose aspirin for healthy adults ages 60 and older. It added that for adults ages 40 to 59 with a 10 percent or greater risk of developing cardiovascular disease over the next 10 years (as assessed by their doctor), the potential net benefit of aspirin use is likely to be minimal.

De Caterina emphasized that the change doesn’t mean that aspirin should not be given to any patients; rather, it should not be given to all patients for primary prevention.

“If you’re healthy, it’s not going to prevent anything,” John J. McNeil, professor at Monash University’s School of Public Health and Preventive Medicine and one of the lead investigators of the ASPREE study, said.

Yet many people are still following the old advice. A 2024 study published in the Annals of Internal Medicine, which analyzed data from more than 186,000 Americans, found that 18.5 percent of adults ages 40 and older reported using aspirin for the primary prevention of cardiovascular disease in 2021. The proportion was even higher among adults ages 60 and older, at nearly 30 percent.

McNeil told The Epoch Times that it takes time to adjust the notion. “Everything in medicine happens very slowly,” he said.

Unexpected Benefit

These findings don’t negate aspirin’s cardiovascular benefits. For people with a history of heart attack or stroke, aspirin is a key part of treatment to prevent recurrence (secondary prevention).

But this was not aspirin’s intended use at first.

Aspirin traces its origins to willow bark, which the Sumerians and Egyptians used more than 3,500 years ago to relieve pain and reduce fever. The therapeutic properties of willow bark come primarily from its salicylic acid content.

In 1897, chemist Felix Hoffmann synthesized acetylsalicylic acid by heating salicylic acid with acetic anhydride. The addition of the acetyl group made salicylic acid more stable.

(Left) Aspirin traces its origins to willow bark. (Right) Generic aspirin inside its bottle. Kalcutta/Shutterstock; Tim Boyle/Getty Images

This compound was registered as “aspirin” and marketed as a fever-reducing, pain-relieving drug. It works by inhibiting prostaglandins—local hormones that trigger inflammation. However, these effects on inflammation are achieved only at high doses of aspirin, typically about 1,000 milligrams per day, or up to 3,000 milligrams (about two to six 500-milligram tablets). Such high doses are not suitable for long-term use because of potential side effects, including gastrointestinal issues.

Researchers noticed a more subtle phenomenon after the drug had been used among the population for some time.

“It was just observed 60 or 70 years later that people who took it regularly seem to have fewer heart attacks or strokes,” Dr. Mark Nelson, chair of general practice at the University of Tasmania’s School of Medicine and professorial research fellow at the Menzies Institute for Medical Research, told The Epoch Times.

Since then, researchers have been working to understand the mechanisms behind this observation.

Nelson said that aspirin’s antithrombotic effect comes from its acetyl group.

Platelets help blood cells clump together to form clots. Low-dose aspirin, through its acetyl group, inhibits an enzyme on platelets, reducing their stickiness and preventing blood clot formation. This inhibition is irreversible; once aspirin binds to a platelet, the platelet remains inactive for the rest of its lifespan, which is about seven to 10 days.

Because about one-seventh of platelets are replaced every 24 hours, patients who have experienced cardiovascular events need to take aspirin daily to maintain its antithrombotic effect.

Its anti-blood-clotting effect is “the only proven mechanism when aspirin is used at the low doses used normally for cardiovascular prevention,” De Caterina said. However, aspirin may benefit only certain groups of people.

Aspirin products on the shelf at a Walgreens drugstore in Chicago on May 26, 2004. Scott Olson/Getty Images

He said that all other factors being equal—such as age and comorbidities—the risk of bleeding from aspirin use is mainly similar for people with and without a history of cardiovascular events. However, because those with prior cardiovascular events face a higher risk of recurrence, the benefits of aspirin in preventing clots are more likely to outweigh the bleeding risk for that group.

Additionally, “the older people are, the more likely they are to bleed,” Nelson said.

“Starting aspirin use as young as 40 years old may have some benefit in preventing a first heart attack and stroke,” Dr. John B. Wong, vice chair of the task force, told The Epoch Times. “Once people turn 60 years old, they should not start taking aspirin because the harms cancel out the benefits.”

Doctors can assess cardiovascular risk using several methods, including risk score calculators that evaluate factors such as blood pressure, cholesterol levels, and smoking status. They may also use ultrasound or computed tomography (CT) scans to examine blood vessels, or they can measure the ankle-brachial index to check for peripheral artery disease. With these tools, doctors can assess who in primary prevention may still benefit from aspirin use.

Too Much of a Good Thing

Clear clinical evidence shows that a daily dose of 75 milligrams to 150 milligrams of aspirin is sufficient to inhibit platelets and prevent blood clots. Exceeding this dose, though, may cause more harm than good.

“When you increase the dose, you don’t increase the antithrombotic efficacy. You only increase gastric toxicity,” De Caterina said.

Prostaglandins play a crucial role in protecting and strengthening the stomach lining while reducing gastric acid secretion. However, aspirin inhibits prostaglandin production, increasing the stomach lining’s permeability and making it more vulnerable to damage from stomach acid. One of the main drawbacks of all nonsteroidal anti-inflammatory drugs, including aspirin, is their gastrointestinal side effects, which may include gastroesophageal reflux, dyspepsia (indigestion), ulcers, and gastrointestinal bleeding.

Illustration by The Epoch Times, Shutterstock

De Caterina said that the types of bleeding associated with aspirin use are primarily subcutaneous bleeding (under the skin) and mucosal bleeding, with the latter mainly affecting the gastrointestinal and urinary tracts.

Gastrointestinal bleeding can cause black, tar-like stools (known as melena) because of blood passing through from the upper gastrointestinal tract. However, Nelson said, not all gastrointestinal bleeding is obvious; some cases may occur without discomfort or visible signs such as melena, instead resulting in anemia as hemoglobin levels gradually decline. Affected individuals may experience fatigue, reduced exercise tolerance, and low energy levels, as their blood can no longer carry oxygen efficiently.

This type of bleeding can also—more rarely—occur in the brain.

“Brain bleeding is usually, however, catastrophic, especially in the elderly, so that will present us with what’s called a hemorrhagic stroke,” Nelson said.

While hemorrhagic strokes account for about 15 percent of all strokes in Western countries, they tend to be more severe and have higher mortality rates than thrombotic strokes. He added that cerebral microbleeds, which may initially go unnoticed, can worsen over time. “You can develop symptoms like dementia,” he said.

In other words, many people take aspirin to prevent thrombotic stroke, but it can have the opposite effect on a different type of stroke. Brain bleeds caused by aspirin are also considered strokes.

“Blood clotting is not a bad thing,” Lufkin said. The body needs the ability to form clots to prevent leaks in blood vessels. Without clotting, we would bleed to death.

“It’s a balance,” he said.

A Remarkable Drug

“Fifteen years ago, I was in Australia accompanied by a prominent American colleague, a scientist who was taking aspirin in primary prevention,” De Caterina said. “Now, it is no longer the case.”

De Caterina said that, even so, aspirin remains a remarkable drug. It functions as an antipyretic and anti-inflammatory agent at high doses, while at low doses, it acts as an antithrombotic agent.

“There is no drug in the world that has been studied more than aspirin in terms of mechanism of action,” he said. “Even in primary prevention, there are still patients who derive a net benefit by taking it.”