Experts Urge Caution on Aspirin Use Among Persons With HF Risk

A new analysis of data from the HOMAGE study addresses previous mixed results on the use of aspirin among patients who may be at risk of heart failure (HF).

Because a 26% greater risk of heart failure (HF) was seen following aspirin use among individuals predisposed to HF, it should be prescribed with caution among this patient group, according to new results from a HOMAGE database analysis published today in ESC Heart Failure.

Mixed results from previous trials on the possibility that aspirin may have no effect on risk of cardiovascular disease and HF spurred this study, which hoped to address the knowledge gaps on a precise role for aspirin at preventing incident HF. The primary end point was a composite of fatal and nonfatal HF, and all participants were followed until death, HF incident, or study’s end. Besides aspirin, they could have no other antithrombotic treatment.

Data were used on 30,827 individuals at risk of developing HF who were enrolled in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT); the Flemish Study on Environment, Genes and Health Outcome (FLEMENGHO); the Health Aging and Body Composition study (HEALTH ABC); the HULL LIFELAB patient study; Valutazione Della Prevalenza di Disfunzione Cardiaca Asintomatica e di Scompenso Cardiaco (PREDICTOR); and the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).

“This is the first study to report that among individuals with a least 1 risk factor for heart failure, those taking aspirin were more likely to subsequently develop the condition than those not using the medication,” said lead study author Blerim Mujaj, MD, PhD, of the University of Freiburg, Germany, in a statement. “While the findings require confirmation, they do indicate that the potential link between aspirin and heart failure needs to be clarified.”

Among the patients included in the final analysis, just over one-third were women, the mean (SD) age was 66.8 (9.2) years, the mean systolic blood pressure (BP) was 157.1 (21.8) mm Hg, the mean diastolic BP was 89.1 (13.2) mm Hg, and 85.8% had hypertension but only 81. 7% were taking antihypertensives.

The authors’ analysis found:

  • Histories of coronary heart disease, stroke, myocardial infarction, and atrial fibrillation among 26.4%, 9.6%, 2.8%, and 1.1%, respectively.
  • Close to 25% were on aspirin therapy at baseline.
  • Overall, 14.5% (95% CI, 13.4%-15.7%) of those in the aspirin group vs 5.9% (95% CI, 5.5%-6.4%) in the nonaspirin cohort experienced fatal or nonfatal HF (over 164,913 total person-years [PY] of follow-up and an average 5.3 years of follow-up).
  • A discovery set analysis of 105,623 PY of follow-up showed 4.3 (95% CI, 3.5-5.3) cases of incident HF in the aspirin cohort vs 2.4 (95% CI, 2.1-2.7) in the nonaspirin cohort, each per 1000 PY.
  • A validation set analysis of 59,289 PY of follow-up showed 24.4 (95% CI, 22.4-26.7) cases of incident HF in the aspirin cohort vs 13.8 (95% CI, 12.7-15.0) in the nonaspirin cohort.
  • Adjusting for confounders (sex, age, body mass index, smoking status, alcohol use, BP, heart rate, blood cholesterol, creatinine, hypertension, diabetes, CVD, antihypertensive treatment) produced a 26% (HR, 1.26; 95% CI, 1.12-1.41; P ≤ .001) increased HF risk among aspirin users.
  • A propensity score–matched analysis showed a 26% (HR, 1.26; 95% CI, 1.10-1.44; P ≤ .001) greater risk of incident HF among aspirin users.
  • Among the 74% of participants with no history of CVD, there was a 27% (HR, 1.27; 95% CI, 1.10-1.46; P = .001) greater risk of incident HF.

The investigators believe their findings are the first to point to a potential link between aspirin use and greater HF risk among those at risk for the disease, and they highlight that possible controversy surrounding aspirin’s use as a cardiovascular disease preventive and secondary prevention method necessitates further investigation in the space.

Because of these conclusions, they recommended prescribing aspirin with caution among persons with a risk of HF.

“Considering the evidence on the risk of HF, the current study demonstrates that cardiovascular benefits associated with aspirin use on HF events require further clarity,” the authors wrote, adding that large multinational randomized trials in adults at risk HF are needed to verify their results.


Mujaj B, Zhang ZY, Yang WY, et al; Heart Omics in Ageing Investigators. Aspirin use is associated with increased risk for incident heart failure: a patient-level pooled analysis. ESC Heart Fail. Published online November 22, 2021. doi:10.1002/ehf2.13688