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Loop diuretics are a standard pharmacologic therapy in heart failure (HF) management. Although furosemide is most frequently used, torsemide and bumetanide are increasingly prescribed in clinical practice, possibly because of superior bioavailability. Few real-world comparative effectiveness studies have examined outcomes across all 3 loop diuretics. The study goal was to compare the effects of loop diuretic prescribing at HF hospitalization discharge on mortality and HF readmission. We identified patients in Medicare claims data initiating furosemide, torsemide, or bumetanide after an index HF hospitalization from 2007 to 2017. We estimated 6-month risks of all-cause mortality and a composite outcome (HF readmission or all-cause mortality) using inverse probability of treatment weighting to adjust for relevant confounders. We identified 62,632 furosemide, 1,720 torsemide, and 2,389 bumetanide initiators. The 6-month adjusted all-cause mortality risk was lowest for torsemide (13.2%), followed by furosemide (14.5%) and bumetanide (15.6%). The 6-month composite outcome risk was 21.4% for torsemide, 24.7% for furosemide, and 24.9% for bumetanide. Compared with furosemide, the 6-month all-cause mortality risk was 1.3% (95% confidence interval [CI]: -3.7, 1.0) lower for torsemide and 1.0% (95% CI: -1.2, 3.2) higher for bumetanide, and the 6-month composite outcome risk was 3.3% (95% CI: -6.3, -0.3) lower for torsemide and 0.2% (95% CI: -2.5, 2.9) higher for bumetanide. In conclusion, the findings suggested that the first prescribed loop diuretic following HF hospitalization is associated with clinically important differences in morbidity in older patients receiving torsemide, bumetanide, or furosemide. These differences were consistent for the effect of all-cause mortality alone, but were not statistically significant., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Study Objectives: Continuous intravenous (IV) infusion bumetanide has been associated with severe myalgia in case reports, and the package labeling lists a reported incidence of 0.2% for severe myalgia. The primary objective of this study was to quantify the incidence of bumetanide infusion-induced severe myalgia in patients with acute heart failure (AHF). Secondary objectives were to assess a dose-response relationship between bumetanide infusion rate and occurrence of myalgia and to investigate potential risk factors associated with bumetanide-induced myalgia., Design: Retrospective analysis., Setting: Large academic medical center., Patients: Adults hospitalized with AHF who required bumetanide (≥ 0.5 mg/hr [464 patients]) or furosemide (≥ 20 mg/hr [197 patients]) by continuous IV infusion between September 2015 and May 2017., Measurements and Main Results: The incidence of severe myalgia with IV furosemide infusion was assessed to measure confounding by indication bias. Electronic medical records were used to identify patients exposed to bumetanide 0.25-mg/ml or furosemide 2-mg/ml continuous IV infusions. We defined severe myalgia as a diffuse myalgia with a physician's documented suspicion of bumetanide- or furosemide-induced myalgia unresponsive to electrolyte repletion and necessitating a change to alternative diuretics. The incidence of severe myalgia during bumetanide therapy was 5.8%, with the incidence increasing with higher bumetanide infusion rates: 2.6% for an infusion rate ≤ 1 mg/hour and 10.3% for a rate > 1 mg/hour (p=0.0005). In the multivariate logistic regression analysis, a bumetanide infusion rate > 1 mg/hour was independently associated (odds ratio 4.8, 95% confidence interval 1.94-12.02, p=0.0007) with severe myalgia compared to that with a rate ≤ 1 mg/hour. No patients receiving furosemide continuous IV infusion experienced severe myalgia, although infusion rates were lower in potency than bumetanide infusion rates., Conclusion: The incidence of severe myalgia in patients with AHF receiving bumetanide infusion was 5.8%, 29-fold higher than incidence rate listed in the package labeling. Patients receiving infusion rates > 1 mg/hour were 4-fold more likely to experience bumetanide-induced severe myalgia than those receiving rates ≤ 1 mg/hour., (© 2019 Pharmacotherapy Publications, Inc.)