Alex M Secora1, Jung-Im Shin2, Yao Qiao2, G Caleb Alexander3, Alex R Chang4, Leslie A Inker5, Josef Coresh2, Morgan E Grams6. 1. Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD. Electronic address: asecora1@jhu.edu. 2. Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD. 3. Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD; Division of General Internal Medicine, Department of Medicine, Johns Hopkins Medicine, Baltimore, MD. 4. Division of Nephrology, Geisinger Health System, Danville, PA. 5. Tufts Medical Center, Department of Internal Medicine, Division of Nephrology, Boston, MA. 6. Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD; Division of Nephrology, Department of Medicine, Johns Hopkins Medicine, Baltimore, MD.
Abstract
OBJECTIVE: To quantify the risk of hyperkalemia and acute kidney injury (AKI) when spironolactone use is added on to loop diuretic use among patients with heart failure, and to evaluate whether the risk is modified by level of kidney function. METHODS: We identified 17,110 patients with heart failure treated with loop diuretics between January 1, 2004, and December 31, 2016 within the Geisinger Health System. We estimated the incidence of hyperkalemia and AKI associated with spironolactone initiation, and used target trial emulation methods to minimize confounding by indication. RESULTS: During a mean follow-up of 134 mo, 3229 of 17,110 patients (18.9%) initiated spironolactone. Incidence rates of hyperkalemia and AKI in patients using spironolactone with a loop diuretic were 2.9 and 10.1 events per 1000 person-months, respectively. In propensity score-matched analyses, spironolactone initiation was associated with higher hyperkalemia and AKI risk compared with loop alone (hazard ratio, 1.69; 95% CI, 1.35 to 2.10; P<.001, and hazard ratio, 1.12; 95% CI, 1.00 to 1.26; P=.04, respectively). There were no differences in the relative risk of either outcome associated with spironolactone by level of kidney function. CONCLUSION: The addition of spironolactone to loop diuretics in patients with heart failure was associated with higher risk of hyperkalemia and AKI; these risks must be weighed against the potential benefits of spironolactone. Published by Elsevier Inc.
OBJECTIVE: To quantify the risk of hyperkalemia and acute kidney injury (AKI) when spironolactone use is added on to loop diuretic use among patients with heart failure, and to evaluate whether the risk is modified by level of kidney function. METHODS: We identified 17,110 patients with heart failure treated with loop diuretics between January 1, 2004, and December 31, 2016 within the Geisinger Health System. We estimated the incidence of hyperkalemia and AKI associated with spironolactone initiation, and used target trial emulation methods to minimize confounding by indication. RESULTS: During a mean follow-up of 134 mo, 3229 of 17,110 patients (18.9%) initiated spironolactone. Incidence rates of hyperkalemia and AKI in patients using spironolactone with a loop diuretic were 2.9 and 10.1 events per 1000 person-months, respectively. In propensity score-matched analyses, spironolactone initiation was associated with higher hyperkalemia and AKI risk compared with loop alone (hazard ratio, 1.69; 95% CI, 1.35 to 2.10; P<.001, and hazard ratio, 1.12; 95% CI, 1.00 to 1.26; P=.04, respectively). There were no differences in the relative risk of either outcome associated with spironolactone by level of kidney function. CONCLUSION: The addition of spironolactone to loop diuretics in patients with heart failure was associated with higher risk of hyperkalemia and AKI; these risks must be weighed against the potential benefits of spironolactone. Published by Elsevier Inc.
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