Nonsteroidal Anti-Inflammatory Drugs and Risk of First Hospitalization for Heart Failure in Patients with No History of Heart Failure: A Population-Based Case-Crossover Study

Introduction Traditional nonselective, nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause salt and fluid retention and should thus be used cautiously in patients with documented heart failure. Recent studies have found that some NSAIDs, including cyclooxygenase (COX)-2 inhibitors, are associated with an increased risk of incident heart failure regardless of the related medical history of the patient. Objective This study aimed to investigate the potential link between NSAIDs (both COX-2 inhibitors and traditional nonselective NSAIDs) and heart failure in patients without a history of heart failure. Methods We conducted a case-crossover study using the National Health Insurance Research Database (NHIRD) in Taiwan. A total of 5615 subjects with a first hospitalization for heart failure between 2005 and 2013 were identified from the NHIRD. Exposure to individual NSAIDs between the case period (1–30 days before the index date) and control period (121–150 days before the index date) were retrieved. Multivariable conditional logistic regression models were used to estimate the adjusted odds ratios (aORs) of the incident heart failure associated with NSAID use after adjustments for potential confounders. Multiple sensitivity analyses, including the case-time-control analysis, were performed to test the robustness of the study results. Results Overall, NSAID use was associated with a 1.58-fold risk [aOR 1.58; 95% confidence interval (CI) 1.40–1.79] of heart failure leading to hospitalization in the main analysis, and similar results were obtained in the case-time-control analysis [aOR 1.40 (95% CI 1.18–1.67)]. The increased risks of heart failure were comparable between traditional NSAIDs [aOR 1.53 (95% CI 1.35–1.74)] and COX-2 inhibitors [aOR 1.74 (95% CI 1.25–2.44)]. Among all NSAIDs, ketorolac was associated with the highest risk of heart failure [aOR 1.98 (95% CI 1.37–2.86)]. Conclusion Both traditional NSAIDs and COX-2 inhibitors were associated with an increased risk of heart failure leading to hospitalization in patients without a related history of heart failure.