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The Aspirin-A-Day Quandary: Do Benefits Outweigh Risks?

by Peter Jaret

Should you take a daily low-dose aspirin to reduce your risk of heart disease? The question seems simple enough. But, after decades of research, it’s proved stubbornly difficult to answer definitively. There’s solid evidence that a daily aspirin (typically 75 to 325 milligrams) protects people already diagnosed with cardiovascular disease (CVD)—an approach called secondary prevention. The evidence, however, has been mixed for daily low-dose aspirin (typically 81 to 100mg) for primary prevention, which is aimed at people who have not been diagnosed with CVD, including having a previous heart attack or stroke.

Aspirin decreases the stickiness of platelets (cells involved in blood clotting), reducing the risk of blood clots that can clog arteries and lead to heart attacks and most strokes. But because aspirin reduces blood clotting, it also raises the risk of bleeding, ranging from easy bruising and nosebleeds to potentially life-threatening gastrointestinal bleeding and hemorrhagic stroke (bleeding in the brain). The question is: Do the benefits exceed those risks?

This year, another round of significant aspirin studies has been published. Each looks at the question from a slightly different angle. The newest findings don’t settle the debate. But they offer important clues for who should and who shouldn’t consider taking a daily aspirin.

ARRIVE, ASCEND, and ASPREE

Like many major research trials these days, three new aspirin studies have memorable acronyms. The international ARRIVE study (Aspirin to Reduce Risk of Initial Vascular Events), which was funded by Bayer HealthCare Pharmaceuticals, focused on the potential benefits and harms of daily aspirin use for people at moderate CVD risk. Researchers recruited more than 12,500 people ages 55 and older in seven countries with risk factors such as high cholesterol, high blood pressure, and a family history of heart disease but excluded people who had diabetes. The participants were randomly assigned a daily enteric-coated low-dose aspirin (100 mg) or a daily placebo sugar pill.

Five years later, participants in both groups had essentially the same low rates of cardiovascular events, such as heart attacks, strokes, and unstable angina—179 of 6,270 patients in the aspirin group and 220 of 6,276 patients in the placebo group. Daily low-dose aspirin offered no statistically significant benefits, according to the findings, published in The Lancet in August 2018. Rates of gastrointestinal bleeding (mostly mild) were also low, but they were higher in the aspirin group (61 patients vs. 29 in the placebo group).

One surprise was how low the overall CVD rates were—so low that participants who were selected because they were at moderate risk, based on a widely used calculation of risk factors, actually proved to be at low risk. That may be because doctors have better information and tools to manage risks today than in the past (such as treating high cholesterol with statins), so the standard calculation used for the study is now outdated. (See box, “Heart Disease Risk Calculator: Due for an Upgrade?”) The bottom line: Low-dose aspirin offered no benefit and slightly increased bleeding risk.

Heart Disease Risk Calculator: Due for an Update?

Although a simple online risk calculator developed by the American Heart Association and the American College of Cardiology is widely used, it remains controversial because it may overstate the risk for some people and understate it for others.

The ASCEND study (A Study of Cardiovascular Events in Diabetes) looked specifically at people with diabetes, which increases heart disease risk two- to threefold. British researchers randomly assigned 15,480 people ages 40 and older with diabetes but no evident CVD to either a daily enteric-coated 100mg aspirin or a daily placebo. After seven years, the aspirin group had a slightly lower rate of heart attacks, strokes, and other CVD events—658 of 7,740 patients in the aspirin group vs. 743 of 7,740 patients in the placebo group. But aspirin-takers also had higher rates of major bleeding (314 patients vs. 245). Publishing their results in the New England Journal of Medicine in August 2018, the researchers concluded that for primary prevention in people with diabetes, the dangers of serious bleeding offset any potential benefits that daily aspirin offered.

Finally, the ASPREE study (ASPirin in Reducing Events in the Elderly) looked at people ages 65 and older. Zeroing in on this population is important since heart disease risk climbs with age, and few studies have looked specifically at the elderly. Conducted in Australia and the United States, the trial recruited more than 19,000 healthy people, with no CVD, dementia, or disability. The participants were randomly assigned to take a daily enteric-coated 100-mg aspirin or a daily placebo.

The findings, published in three papers in the New England Journal of Medicine in September 2018, showed no significant differences between the two groups nearly five years later—both had similar rates of CVD events, disability, and dementia. The aspirin group, though, had a higher bleeding rate, including gastrointestinal bleeding and hemorrhagic strokes (361 of 9,525 patients vs. 265 of 9,589 patients in the placebo group). The aspirin group also had more deaths at 558 vs. 494 in the placebo group.

The role of body weight

On balance, then, the latest findings show that the risks of low-dose aspirin might outweigh the benefits for many people. But one additional study published in The Lancet in August 2018, suggests that body weight might play a role in aspirin’s effectiveness. Body weight affects how people metabolize many different medications (the larger you are, the higher dose you may need for a drug to be effective). High body mass index, or BMI (an estimation of body fat based on height and weight), may also alter the way aspirin is metabolized.

An international research team led by scientists from the University of Oxford in England analyzed data from nine trials and found that the typical low-dose aspirin regimen (75 to 100 mg/day) protected against cardiovascular disease only in individuals who weighed less than 154 pounds. Higher doses (300 mg or higher) were effective in individuals weighing 154 pounds or more.

The results suggest that adjusting the dose to an individual’s weight might improve aspirin’s effectiveness in primary and secondary prevention. The results may also explain why its benefits haven’t been as evident as researchers first hoped. When the scientists analyzed data for all participants, regardless of body weight, the results showed that low-dose aspirin reduced cardiovascular events by about only 12 percent. When they looked specifically at individuals weighing less than 154 pounds that number jumped to 23 percent lower risk.

The Aspirin-Cancer Link

In 2016, the U.S. Preventive Services Task Force issued the first-ever recommendations for daily aspirin to prevent colorectal cancer. The recent batch of new low-dose aspirin findings doesn’t alter those recommendations, but more research is needed.

What should you do?

There’s still a lot to be learned about the potential benefits of taking a daily aspirin. In the past, the use of statins and more aggressive high blood pressure treatment wasn’t as widespread as it is today, so any benefit aspirin may convey for primary prevention might be smaller than it once was.

That said, if you’re already taking low-dose aspirin, don’t stop taking it without consulting your doctor first. At least one study suggests that suddenly stopping aspirin might increase the risk of a heart attack or a stroke, possibly because of a “rebound” effect in blood clotting that can occur (especially in people who have had a previous cardiovascular event).

Conversely, don’t start taking aspirin without consulting with your doctor about your individual risks and benefits. In 2015, the U.S. Preventive Services Task Force (USPSTF)—a federal panel of medical experts that evaluates evidence for preventive medical protocol—recommended aspirin therapy in an 81 mg dose (as in a baby aspirin) as primary prevention to people in their 50s who are at high cardiovascular risk (10 percent or higher risk of a heart attack or stroke over the next 10 years, based on a standard risk calculator) but not at increased bleeding risk. The USPSTF also recommended a daily aspirin for high-risk people in their 60s but with extra caution because bleeding risk is greater and aspirin’s net benefit smaller in older people. For people under age 50 or over 70, the USPSTF concluded that there wasn’t enough evidence to make recommendations.

It’s important to remember that the best ways to lower your heart disease risk are to get your cholesterol and blood pressure measured regularly and follow your doctor’s treatment advice if your numbers are too high. Losing excess weight if you’re overweight or obese and being active also goes a long way toward protecting your heart. Even if a daily aspirin isn’t right for you, there’s plenty you can do to lower your risk.

This article first appeared in the December 2018 issue of UC Berkeley Health After 50.

Also see Beware of Stopping Low-Dose Aspirin Therapy.