Aspirin is ineffective in preventing heart attack, stroke and death in heart failure patients without atrial fibrillation (AFib), according to a nationwide study in Denmark. In fact, patients on aspirin may be more likely to have myocardial infarction (MI) or be rehospitalized for heart failure, Christian Madelaire, MD, and colleagues reported in JACC: Heart Failure.
“The findings cast further doubt on the benefit associated with the use of aspirin in patients with HF (heart failure),” the researchers wrote. “A prospective, randomized clinical trial could be relevant.”
The study included 12,277 patients with new-onset heart failure and no history of AFib. Madelaire et al. matched 3,840 patients on low-dose aspirin (75 mg/day) by age, sex and comorbidities to the same number of patients who weren’t taking aspirin. The matched participants were 78 years old on average and 52 percent were female.
After a median follow-up of 1.7 years, the researchers found no significant difference in the composite outcome of all-cause mortality, MI and stroke. However, the absolute rates of MI (4.8 percent vs. 3.6 percent) and hospitalization for heart failure (31 percent vs. 29 percent) were higher among aspirin users, translating to relative risk increases of 34 and 25 percent, respectively.
“The increased risk of heart failure hospitalization is consistent with many, although not all, previous analyses and, if true, equates to a number needed to harm of just 48,” wrote John G.F. Cleland, MD, in an accompanying editorial. “The effect on myocardial infarction could just reflect residual confounding but certainly does not provide evidence of benefit from aspirin.”
Madelaire and colleagues found a nonsignificant increase in major bleeding occurred in the aspirin group, but those figures only included hospital admissions. Had minor bleeding events treated elsewhere or in the emergency room also been included, the authors hypothesized there would have been a larger gap between the groups.
Patients with more severe heart failure were less likely to meet the primary outcome if they were on aspirin, primarily because they showed a 44 percent reduction in stroke risk. Also, patients who were taking aspirin in addition to either statins or beta-blockers had a reduced risk of all-cause mortality and stroke, but maintained a higher risk of MI.
“Aspirin may contribute to hemorrhage in existing plaques and thus contribute to progression and instability of the plaque, which increases the risk of MI,” the researchers wrote.
However, they acknowledged residual confounding may have factored into that result.
The increase in hospitalizations associated with aspirin, Madelaire and colleagues wrote, “could be partly explained by impaired renal function caused by aspirin, which subsequently could contribute to salt and water retention and worsened HF. It has previously been suggested that aspirin could reduce the effect of angiotensin-converting enzyme inhibitors when these drugs are used simultaneously.”
In his editorial, Cleland pointed to the lack of placebo-controlled trials evaluating the long-term use of aspirin.
“Aspirin is a fine example of the mess created by people jumping to premature conclusions based on wishful thinking and flawed data,” wrote Cleland, with the Robertson Centre for Biostatistics and Clinical Trials at the university of Glasgow in Scotland. “Ideally, further randomized, placebo-controlled trials should be conducted. This approach requires that patients and physicians agree that it is foolish to continue to ignore the possibility that aspirin is a waste of time or worse. An environment conducive to fresh trials will only be possible if the intellectual equipoise that uncertainty provides is restored.”