Sung-Po Huang1, Yao-Chun Wen2, Shih-Tsung Huang3, Chih-Wan Lin3, Tzung-Dau Wang4,5, Fei-Yuan Hsiao6,7,8. 1. School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. 2. Health Data Research Center, National Taiwan University, Taipei, Taiwan. 3. Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, 33, Linsen S. Rd, Taipei, 10050, Taiwan. 4. College of Medicine, National Taiwan University, Taipei, Taiwan. 5. Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 6. School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. fyshsiao@ntu.edu.tw. 7. Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, 33, Linsen S. Rd, Taipei, 10050, Taiwan. fyshsiao@ntu.edu.tw. 8. Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan. fyshsiao@ntu.edu.tw.
Abstract
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.
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.
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