Discontinuing primary preventive aspirin didn't appear to increase mortality risk
Regular aspirin users who were switched to placebo in a randomized trial did not have increased risk of all-cause mortality or cardiovascular disease events compared with those who continued aspirin, but the findings of the post hoc analysis were inconclusive.
Physicians can consider a pragmatic recommendation to stop aspirin for primary prevention in those with a large medication burden and with due caution, a study found.
To investigate the effect of aspirin cessation on survival and other clinical outcomes, researchers conducted a post hoc analysis of ASPREE (ASPirin in Reducing Events in the Elderly), a randomized, double-blind, placebo-controlled primary prevention trial of aspirin. This analysis looked at participants who reported taking aspirin two or more days per week at enrollment. The primary outcome was a composite of all-cause mortality, incident dementia, or persistent disability-free survival. Secondary outcomes were all-cause mortality, major adverse cardiovascular events, any cardiovascular event, major hemorrhage, and cancer. Results were published as a brief research report March 15 by Annals of Internal Medicine.
Of a cohort of 19,114 patients, 2,094 (11%) reported using aspirin and 1,714 reported taking it two or more days per week. Over a median follow-up of 4.9 years, evidence that ceasing aspirin therapy increased risk for the primary outcome was weak and confined to non-White participants. Overall, 116 of 841 participants (13.8%) in the cessation group and 97 of 873 (11.1%) in the continuation group experienced the primary end point (incidence rate, 29.8 vs. 23.4 per 1,000 person-years). The hazard ratio for cessation versus continuation was 1.28 (95% CI, 0.98 to 1.68).
When the analysis was restricted to those taking prior aspirin six or more days per week, the hazard ratio for cessation versus continuation was 1.20 (95% CI, 0.89 to 1.60). Although aspirin cessation was not associated with any secondary outcome, it appeared to increase cardiovascular disease events among those who reported taking aspirin for five years or longer. Age had no evident impact on the effect of aspirin cessation, the study authors noted.
Continued aspirin use showed no substantial increased risks for major hemorrhage and cancer, although self-selection for tolerance among aspirin users may have resulted in absence of an effect on hemorrhage, the study authors said. They noted that the analyses are likely underpowered and that findings did not conclusively show clear harm or benefit of aspirin cessation or continuation in older adults. Other limitations include the post hoc study and a four-week placebo run-in phase for the trial before randomization, which created a gap in continuous exposure for those randomly assigned to aspirin.
“However, given the community sampling frame and the findings of the main study, at this time, a pragmatic recommendation may be to consider aspirin cessation in those with a large medication burden with due caution,” the authors wrote.
An accompanying editorial noted that results should be interpreted with the limitations of a post hoc subgroup analysis in mind, so replication is needed.
“[I]t is worth emphasizing that the 2019 [American College of Cardiology/American Heart Association] primary prevention guideline recommendation on aspirin among older adults included the text ‘should not be used on a routine basis' specifically to allow clinicians and patients some room to consider continuing aspirin among select adults over age 70 years, like when ischemic [cardiovascular disease] risk remains very high but competing and bleeding risks are low,” the editorial concluded.