Does aspirin increase HF risk?

Individuals with risk factors for heart failure (HF) may have an increased risk of developing the condition if they are aspirin users, results of the HOMAGE* study showed.

“[I]n our study, one in four participants were taking [aspirin]. In this population, aspirin use was associated with incident HF, independent of other risk factors,” said study author Dr Blerim Mujaj from the University of Freiburg, Freiburg, Germany.

Using data from six observational studies, the researchers identified 30,827 patients aged ≥40 years (mean age 66.8 years, 33.9 percent female) without HF but with a risk for developing HF**. Patients were documented as users or non-users of aspirin (24.9 percent were aspirin users) and were not on any other antithrombotics.

About 22 percent of patients had diabetes, 26.4 percent were current smokers, and 66.7 percent consumed alcohol. A total of 26,453 patients had hypertension, 81.7 percent of whom were on antihypertensive medications. Twenty-six percent had a history of coronary heart disease, while 2.8, 9.6, and 1.1 percent had a history of myocardial infarction, stroke, and atrial fibrillation, respectively.

A total of 1,330 patients developed fatal or non-fatal HF over a median 5.3-year follow-up period. The incidence rate for HF was 14.5 vs 5.9 per 1,000 person-years in aspirin users and non-users, respectively.

Aspirin use was associated with an increased risk of incident HF (composite of fatal and non-fatal HF; adjusted hazard ratio [adjHR], 1.26, 95 percent confidence interval [CI], 1.12–1.41; p<0.001). [ESC Heart Fail 2021;doi:10.1002/ehf2.13688]

The risk of HF with aspirin use was still elevated when analysed in the 22,690 patients without a history of cardiovascular disease (adjHR, 1.27, 95 percent CI, 1.10–1.46; p=0.001) and when excluding patients who developed incident HF in the first 2 years of follow-up (adjHR, 1.23, 95 percent CI, 1.06–1.41; p=0.004).

The interaction between systolic or diastolic blood pressure and aspirin use was not significant. In aspirin users, there was a trend toward a higher risk of HF among patients who were not on diuretics vs diuretic users at baseline (adjHRs, 1.38 vs 1.14; p_interaction=0.02) and in statin users vs non-users (adjHRs, 1.50 vs 1.19; p_interaction=0.04). The risk of incident HF was also elevated in men (HR, 1.37; p_interaction=0.04) and in patients aged >69 years (p_interaction=0.03).

The use of aspirin in primary and secondary prevention is controversial, said Mujaj and co-authors.

“This is the first study to report that among individuals with a least one risk factor for HF, those taking aspirin were more likely to subsequently develop the condition than those not using the medication,” said Mujaj. “While the findings require confirmation, they do indicate that the potential link between aspirin and HF needs to be clarified.”

Mujaj called for “large multinational randomized trials” in similar populations to verify the findings of the HOMAGE study. “Until then, our observations suggest that aspirin should be prescribed with caution in those with HF or with risk factors for the condition,” he concluded.

The authors acknowledged that information on use of aspirin and other medications was only collected at enrolment and changes in medication use were not factored in this study, nor was medication adherence. The effect of aspirin dose on outcomes could also not be ascertained. HF incidence was limited to HF hospitalizations and was not differentiated between ischaemic and non-ischaemic HF or according to ejection fraction.