Long-Term Aspirin Use and Heart Failure Incidence: A Patient-Level Pooled Analysis Study.

Background: The effect of chronic aspirin use on the development of heart failure remains uncertain, and no prior observational study has evaluated it as a time-dependent exposure.

Methods: We analyzed data from four prospective cohort studies involving 26,941 individuals free of cardiovascular disease but at risk for heart failure. The baseline mean age was 60.7 years; 55.6% were female and 65.4% were White. Time-dependent information on aspirin use and heart failure risk factors was systematically collected, and participants were longitudinally followed for incident heart failure. Using the parametric g-formula, we estimated the effect of two hypothetical interventions-consistent aspirin use and never using aspirin-on heart failure incidence. Covariates included baseline age, sex, race, smoking, alcohol consumption, study-related factors, and time-dependent variables such as body mass index, systolic blood pressure, low-density lipids, triglycerides, blood glucose, creatinine, and medication use (anti-hypertensive, anti-diabetic, lipid-lowering, and anticoagulant).

Results: Over a median follow-up of 14.8 years (IQR: 8.5-22.5), 5,899 heart failure cases occurred. At year 32, as estimated by the model and compared with the natural course (no intervention), continuous aspirin use increased heart failure risk by 7% (risk ratio [RR] 1.07, 95% CI 1.05-1.08), while never using aspirin decreased risk by 6% (RR 0.94, 95% CI 0.92-0.95). These effects persisted in subgroup analyses by sex and by baseline age (<60/≥60 years).

Conclusion: Long-term aspirin use increased the risk of heart failure in individuals free of cardiovascular disease, as estimated through a hypothetical intervention using the g-formula.