Aspirin in Older Adults Linked to Fewer Deaths

Liam Davenport

December 11, 2019

UPDATED WITH COMMENTS December 12 — A new analysis has found that older adults (> 65 years) who regularly took aspirin had a significant reduction in mortality from all causes and from cancer compared with individuals who didn't take aspirin.  

"This observation was consistent across all causes of mortality...however, the greatest reduction in risk was noted for colorectal cancer (CRC) mortality among individuals who used aspirin three or more times per week," say the researchers.

The risk of dying from any cause was reduced by 19%, from any cancer by 15%, from GI cancer by 25%, and from CRC by 29%.

The findings come from a new analysis of data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, which involved more than 145,000 individuals. The study was funded by grants from the National Cancer Institute and the Stuart and Suzanne Steele MGH Research Scholarship.

The new results are reported by Holli A. Loomans-Kropp, PhD, MPH, Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland, and colleagues, who note that the impact of aspirin on mortality risk appears to be modulated by body mass index (BMI).

"The efficacy of aspirin as a cancer preventive agent may be associated with BMI," they write. Participants who were underweight (ie, BMI < 20 kg/m2) had no observable benefit associated with aspirin use but aspirin use in those with a BMI ≥ 20 kg/m2 was associated with reduced mortality risk. The greatest reductions in mortality risk were seen in individuals with a higher BMI (25–29.9 kg/m2).

The study was published in the December issue of JAMA Network Open.

The authors acknowledge that their findings require "further confirmation" and note that the significant reduction in mortality associated with aspirin use contrasts with results from other studies. Nevertheless, they say that their finding of an impact of BMI on the effect of aspirin suggests the "increasing rates of overweight and obesity globally may substantially alter the population-based efficacy of cancer prevention prophylactics."

Recent Study Showed Higher Mortality

The new findings of a significant reduction in mortality are in stark contrast to recent data from the United States and Australia, which showed higher mortality in individuals taking aspirin. 

Those data come from the Aspirin in Reducing Events in the Elderly (ASPREE) study, which examined the efficacy of 100-mg aspirin in individuals aged ≥ 70 years in the United States and Australia (≥ 65 years for US black or Hispanic participants). As reported by Medscape Medical News, the study showed higher all-cause and cancer-related mortality with aspirin therapy.

Loomans-Kropp says the new findings add "to what's already known about the use of aspirin as a cancer preventative mechanism."

She continued: "It's something for people to keep in mind when they're considering whether or not to begin taking aspirin according to either doctor’s recommendations or whatever recommendations they choose to look at."

Approached for comment, Michael N. Passarelli, PhD, Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, told Medscape Medical News that the results from ASPREE were "very unexpected," and the current study "supports what was our knowledge before ASPREE."

He noted that, based on ASPREE and two other recent studies, "there has been some major rethinking of clinical recommendations for daily aspirin use, specifically among older people."

However, he underlined that "we're still in an uncertain place," and that the design of ASPREE and the current analysis were quite different.

"[The current analysis] is a very large study. It has strength because of its long duration of follow-up and its size; it's much larger than ASPREE," he said.

Passarelli continued: "It just doesn't have that strength of having randomized aspirin versus placebo. It's looking at the natural occurrence of aspirin as reported by the participants, so there's a lot of other factors related to the choice of using aspirin that could explain these results."

Aspirin Taken for Various Reasons

In an interview with Medscape Medical News, Loomans-Kropp explained that for the current study, her team created an aggregate measure of aspirin use that could be used as a surrogate longitudinal measure.

"We collapsed the aspirin use frequency variables into no aspirin use or less than once per month, one to three times per month, one to two times per week, and three or more times per week," the team explains in the article.

Consequently, the use of aspirin by the trial participants could reflect various reasons for taking the drug.

"At least for the US population, aspirin is readily available, so they could be taking it for relatively minor pain relief throughout the week," Loomans-Kropp said.

"It could be that individuals are using aspirin as a cancer preventative agent, as it’s part of the US Preventive Services Task Force [USPSTF] recommendations," she said. But it could also be that individuals are taking aspirin to reduce cardiovascular risk.

The USPSTF recommends low-dose aspirin for cardiovascular disease and CRC prevention in certain individuals aged 50–59 years. However, the Task Force also recommends an individualized approach for those aged 60–69 years, and note the evidence in individuals at least aged 70 years is considered insufficient.

Details of the New Analysis

The PLCO Cancer Screening Trial ran from 1993-2001 at 10 centers in the United States, and individuals aged 55-74 years were randomized to either a screening or control group.

The current analysis looked at participants aged ≥ 65 years at baseline or who had survived until 65 years, and who had a valid baseline questionnaire and reported their aspirin use.

The study involved 146,152 individuals with a mean age at baseline of 66.3 years. Just over half (51.1%) were women and 88.6% were non-Hispanic white.

Over a median follow-up of 12.5 years, 40,419 individuals died, including 12,421 who died of any cancer and 1425 who died of gastrointestinal cancer (814 from CRC, 353 from esophageal cancer, and 258 from gastric cancer).

The team found that any use of aspirin was associated with reduced all-cause and cancer-specific mortality.

Specifically, aspirin use from one to three times per month was associated with a reduced risk of all-cause mortality compared with no use, at a hazard ratio of 0.84 (P < .001), as well as cancer mortality, at a hazard ratio of 0.87 (P < .001).

Aspirin use three or more times a week was also associated with a decreased risk of all-cause mortality versus no use, at a hazard ratio of 0.81 (P < .001), and cancer mortality, at a hazard ratio of 0.85 (P < .001).

In addition, aspirin use at least three times a week was linked to significantly reduced gastrointestinal cancer mortality versus no aspirin use, at a hazard ratio of 0.75 (P < .001), and CRC, at a hazard ratio of 0.71 (P < .001).

When researchers stratified participants by BMI, they found the impact of aspirin use appeared to be greater in more overweight individuals.

Among people with a BMI of 20–24.9 kg/m2, aspirin use at least three times a week was associated with a reduced risk of all-cause mortality versus no use, at a hazard ratio of 0.82 (P < .001), and cancer mortality, at a hazard ratio of 0.86 (P < .001).

For individuals with a BMI of 25–29.9 kg/m2, aspirin use three times a week or more was associated with reduced all-cause mortality and cancer mortality compared with no use, at hazard ratios of 0.82 and 0.86, respectively (P < .001 for both).

In addition, there was a reduced risk of gastrointestinal cancer mortality, at a hazard ratio of 0.72 (P < .001), and CRC mortality, at a hazard ratio of 0.66 (P = .001), in this group with thrice weekly or more aspirin use.

Passarelli commented that the BMI results are "not one of the most important takeaways from this study."

"It's difficult to say whether this is really biological or a consequence of the fact that very few older people have a BMI that low, which affects precision in a study like this," he explained.

"The vast majority (over 95% in this study) have a BMI over 20 kg/m2, and the aspirin association actually seemed pretty consistent across BMI categories over 20 kg/m2," he added.

Passarelli believes that, based on the current evidence, "it's not clear whether aspirin recommendations should be altered to account for a patient's weight or body mass index."

He said that recent research has suggested higher doses of aspirin "may be necessary among those who weigh more."

"I think any future study would probably probe that a lot further by considering a sort of tailored, personalized aspirin dosing approach — a specific dose according to age, weight, and other comorbidities — to see if we can ideally strike a balance between any of these long-term benefits and the more immediate harms related to gastrointestinal bleeding," Passarelli said.

JAMA Netw Open. 2019;2:e1916729. Full text

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