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.
Abbreviations and Acronyms:
ACEi (angiotensin-converting enzyme inhibitor), ARB (angiotensin II receptor blockers), AKI (acute kidney injury), CVD (cardiovascular disease), CCI (Charlson comorbidity index), CKD (chronic kidney disease), eGFR (estimated glomerular filtration rate), EHR (electronic health record), HFpEF (heart failure with preserved ejection), HFrEF (heart failure with reduced ejection), ITT (intention-to-treat), K (potassium), PAD (peripheral artery disease), PS (propensity score), RALES (Randomized Aldactone Evaluation Study), SCr (serum creatinine), sHR (subdistribution hazard ratios), TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist)To read this article in full you will need to make a payment
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Article Info
Footnotes
Potential Competing Interests: Dr Shin is a principal investigator of a grant provided to the Johns Hopkins Bloomberg School of Public Health from Merck . Dr Alexander is past Chair of the US Food and Drug Administration’s Peripheral and Central Nervous System Advisory Committee; has served as a paid advisor to IQVIA; serves as a consultant and holds equity in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation; and is a member of OptumRx’s National P&T Committee. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies. Dr. Inker has consulting agreements with Tricida and Omeros Corp. The remaining authors report no potential competing interests.
Grant Support: Dr Secora was supported by grant T32 HL007024 from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH). Dr Gram is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ( R01 DK100446 and R01 DK115534 ). Dr Alexander is supported by 1 U01 FD004977-02 from the U.S. Food and Drug Administration (FDA). Dr Chang is supported by a grant from the NIDDK ( K23 DK106515 ). Dr Shin is supported by a grant from the NIDDK ( K01 DK121825 ). Dr. Inker is supported by grants from NIDDK (R01DK115534 and U01DK085689), and funding from Retrophin, Omeros, Dialysis Clinics, Inc., and Reata Pharmaceuticals for research and contracts to Tufts Medical Center.
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