An Aspirin a Day for Older People Doesn’t Prolong Healthy Lifespan

Posted on September 25th, 2018 by Dr. Francis Collins

Many older people who’ve survived a heart attack or stroke take low-dose aspirin every day to help prevent further cardiovascular problems [1]. There is compelling evidence that this works. But should perfectly healthy older folks follow suit?

Most of us would have guessed “yes”—but the answer appears to be “no” when you consider the latest scientific evidence. Recently, a large, international study of older people without a history of cardiovascular disease found that those who took a low-dose aspirin daily over more than 4 years weren’t any healthier than those who didn’t. What’s more, there were some unexpected indications that low-dose aspirin might even boost the risk of death.

The long-awaited results of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, partly funded by NIH, were presented in three papers just published in the New England Journal of Medicine [2,3,4]. It’s the largest primary prevention study ever undertaken in healthy older people.

Right now, millions of people around the world take aspirin to help prevent heart disease. The century-old drug works by making platelets in the blood less sticky and therefore less likely to clot. However, the effect of aspirin on platelets also comes with an increased risk of bleeding.

What’s been unclear is whether the potential benefits outweigh the risks of healthy older people taking a low-dose aspirin each day. That’s because there’s been a lack of solid scientific evidence.

To take a closer look, a research team led by John McNeil, Monash University, Melbourne, Australia, and Anne Murray, Hennepin Healthcare Research Institute, Minneapolis, launched the ASPREE trial in 2010. The trial enrolled more than 19,000 healthy older people, aged 70 or older, who did not have cardiovascular disease, dementia, or disability. Because African Americans and Hispanic Americans have a higher risk for dementia and heart disease, they could enroll in the trial at age 65 and up.

Half of the study’s participants were randomly assigned to take 100 milligrams of aspirin each day. The other half took a placebo sugar pill. During the median 4.7 years of follow up, researchers called participants three times a year to find out how they were doing. Trial participants also came in for annual visits, during which researchers conducted cognitive and functional testing and reviewed their medical records.

When the study wrapped up in June 2017, about 90 percent of the participants were alive and well, without any persistent disability or dementia. That was true whether they’d been taking a daily aspirin or not.

The rates for major cardiovascular events were also similar between the two groups. Among those who took aspirin, 448 had a cardiovascular event—such as coronary heart disease, fatal or non-fatal heart attacks, and fatal or non-fatal ischemic stroke—during the study. That’s compared to 474 people who took the placebo pill instead. So, while there might have been a small protective effect, this was not statistically significant.

Neither did regular aspirin use significantly prolong healthy lifespan, free of dementia, disability, or cardiovascular problems. But, it did lead to a significant increase in bleeding, primarily in the gastrointestinal tract and brain. Among those who took a daily aspirin, 361 suffered a significant bleeding event requiring a blood transfusion or hospitalization. Bleeding events occurred in about 100 fewer people—265—in the placebo group.

During the 4.7 years of follow up, more than 1,000 study participants died, with about half of those deaths related to cancer. Heart disease and stroke accounted for about 20 percent of the deaths and major bleeding about 5 percent. Importantly, the risk of death due to all causes was slightly higher for people taking aspirin. Almost 6 percent of participants taking aspirin died during the study compared to closer to 5 percent for those taking placebo. That may sound like a small difference, but it represents about 100 additional deaths in the aspirin-treated group.

What was the cause of death? The higher mortality observed in healthy older people taking aspirin was attributed primarily to cancer-related deaths. That’s a surprise given previous studies suggesting regular aspirin use offers protection against certain cancers.

The researchers say it’s still possible that the differences in mortality between the two groups might be explained by chance. They’re now conducting further in-depth analyses of all the cancer-related data from the trial. Hopefully, they’ll have some additional insight to share with us soon. Keep in mind that cancer grows slowly—so that most cancers are present for years before being diagnosed. If aspirin led to increased cancer deaths in this seven-year study, it’s more likely that it accelerated the course of preexisting malignancies, rather than initiating entirely new cancers.

It remains to be seen whether daily aspirin could come with some longer-term benefits for older people, and the researchers hope to continue monitoring the study’s remaining participants to find out. For older people now taking aspirin, it’s best to consult with your doctors before making any changes to your medications. But, for now, it appears that if you’re a healthy older person with no history of cardiovascular disease, an aspirin a day may not have the potential we once thought to keep the doctor away.

References:

[1] Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Preventive Medication. U.S. Preventive Services Task Force.

[2] Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly. McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR, Reid CM, Lockery JE, Kirpach B, Storey E, Shah RC, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Johnston CI, Ryan J, Radziszewska B, Jelinek M, Malik M, Eaton CB, Brauer D, Cloud G, Wood EM, Mahady SE, Satterfield S, Grimm R, Murray AM; ASPREE Investigator Group. N Engl J Med. 2018 Sep 16.

[3] Effect of Aspirin on Disability-free Survival in the Healthy Elderly. McNeil JJ, Woods RL, Nelson MR, Reid CM, Kirpach B, Wolfe R, Storey E, Shah RC, Lockery JE, Tonkin AM, Newman AB, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Donnan GA, Gibbs P, Johnston CI, Ryan J, Radziszewska B, Grimm R, Murray AM; ASPREE Investigator Group. N Engl J Med. 2018 Sep 16.

[3] Effect of Aspirin on All-Cause Mortality in the Healthy Elderly. McNeil JJ, Nelson MR, Woods RL, Lockery JE, Wolfe R, Reid CM, Kirpach B, Shah RC, Ives DG, Storey E, Ryan J, Tonkin AM, Newman AB, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Donnan GA, Gibbs P, Johnston CI, Radziszewska B, Grimm R, Murray AM; ASPREE Investigator Group. N Engl J Med. 2018 Sep 16.

Links:

ASPREE Trial (Hennepin Healthcare Research Institute, Berman Center for Outcomes & Clinical Research, Minneapolis)

John McNeil (Monash University, Melbourne, Australia)

Anne Murray (Hennepin Healthcare Research Institute, Berman Center for Outcomes & Clinical Research)

NIH Support: National Cancer Institute; National Institute on Aging