Clinical characteristics and outcomes of nonsteroidal anti-inflammatory drug-related heart failure in real-world Japanese practice: a retrospective cohort study

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for musculoskeletal pain, their use in patients with heart failure (HF) is discouraged because of risks of fluid retention and worsening disease. Nevertheless, in older patients, NSAIDs are still prescribed by non-cardiologists. We conducted a single-center retrospective cohort study of patients aged ≥ 65 years who were hospitalized for acute decompensated HF at Yamaguchi Prefectural General Medical Center between January 2016 and January 2022. Patients were classified as NSAIDs-related HF if NSAIDs use for ≥ 1 week before admission was identified through pharmacist review. As part of comprehensive cardiac rehabilitation, all patients received self-management guidance on medications, including NSAIDs avoidance. Multivariate Cox proportional hazards models were applied to assess associations with clinical outcomes. Among 801 patients, 64 (8.0%) were classified as NSAIDs-related HF and 737 (92.0%) as NSAIDs-unrelated HF. NSAIDs-related HF cases more frequently represented first-time HF hospitalizations. For the primary endpoint of all-cause mortality or HF readmission, the NSAIDs-related group showed a trend toward improved outcomes, although the difference did not reach statistical significance (hazard ratio [HR] 0.569, 95% confidence interval [CI] 0.289-1.118; p = 0.102). In contrast, the incidence of the secondary endpoint, major adverse cardiac and cerebrovascular events (MACCE), was significantly lower in the NSAIDs-related group (HR 0.404, CI 0.178-0.917; p = 0.030). NSAIDs-related HF accounted for a modest proportion of new HF hospitalizations in older patients. After standard management and NSAIDs discontinuation, outcomes were comparable to those of other HF patients, with a trend toward fewer adverse events. These findings likely reflect differences in patient background and comprehensive rehabilitation rather than a direct protective effect of discontinuation.