Akshay S Desai1, Jiankang Liu2, Marc A Pfeffer2, Brian Claggett2, Jerome Fleg3, Eldrin F Lewis2, Sonja McKinlay4, Eileen O'Meara5, Sanjiv J Shah6, Nancy K Sweitzer7, Scott Solomon2, Bertram Pitt8. 1. Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: adesai@partners.org. 2. Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. 3. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. 4. New England Research Institutes, Inc., Watertown, Massachusetts. 5. Institut de Cardiologie de Montréal, Université de Montréal, Montréal, Canada. 6. Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 7. Sarver Heart Center, University of Arizona, Tucson, Arizona. 8. Cardiovascular Division, University of Michigan School of Medicine, Ann Arbor, Michigan.
Abstract
BACKGROUND: In patients with heart failure and preserved ejection fraction (HF-PEF) randomized in the Americas as part of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, treatment with spironolactone enhanced the risk of hyperkalemia but reduced the risk of hypokalemia. We examined the clinical correlates and prognostic implications of incident hypo- and hyperkalemia during study follow-up. METHODS: We defined the region-specific incidence of hypokalemia (potassium [K+] <3.5 mmol/l) and hyperkalemia (K+ ≥5.5 mmol/l) among both placebo- and spironolactone-assigned patients in TOPCAT. Factors associated with incident hypokalemia and hyperkalemia and the relationship between incident K+ abnormalities and the risk of subsequent mortality were analyzed in multivariable regression models restricted to the Americas. RESULTS: In the Americas, assignment to spironolactone increased risk for hyperkalemia (hazard ratio 3.21, 95% confidence interval 2.46-4.20, P < .001) and reduced risk of hypokalemia (hazard ratio 0.43, 95% confidence interval 0.34-0.55, P < .001). Assignment to spironolactone, lower estimated glomerular filtration rate, higher baseline K+, diabetes, and lower hemoglobin were associated with incident hyperkalemia, whereas assignment to placebo, lower K+, younger age, lower estimated glomerular filtration rate, and use of diuretics at baseline were associated with hypokalemia. The combination of spironolactone and an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker was associated with incremental risk for hyperkalemia and protection from hypokalemia. Independent of region, both hypokalemia and hyperkalemia, were associated with higher risk for cardiovascular and all-cause mortality in multivariable-adjusted Cox regression models. CONCLUSIONS: Both hyperkalemia and hypokalemia are associated with heightened risk for mortality in HF-PEF. Use of spironolactone in this population requires careful laboratory surveillance of K+ and creatinine, particularly in high-risk groups.
BACKGROUND: In patients with heart failure and preserved ejection fraction (HF-PEF) randomized in the Americas as part of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, treatment with spironolactone enhanced the risk of hyperkalemia but reduced the risk of hypokalemia. We examined the clinical correlates and prognostic implications of incident hypo- and hyperkalemia during study follow-up. METHODS: We defined the region-specific incidence of hypokalemia (potassium [K+] <3.5 mmol/l) and hyperkalemia (K+ ≥5.5 mmol/l) among both placebo- and spironolactone-assigned patients in TOPCAT. Factors associated with incident hypokalemia and hyperkalemia and the relationship between incident K+ abnormalities and the risk of subsequent mortality were analyzed in multivariable regression models restricted to the Americas. RESULTS: In the Americas, assignment to spironolactone increased risk for hyperkalemia (hazard ratio 3.21, 95% confidence interval 2.46-4.20, P < .001) and reduced risk of hypokalemia (hazard ratio 0.43, 95% confidence interval 0.34-0.55, P < .001). Assignment to spironolactone, lower estimated glomerular filtration rate, higher baseline K+, diabetes, and lower hemoglobin were associated with incident hyperkalemia, whereas assignment to placebo, lower K+, younger age, lower estimated glomerular filtration rate, and use of diuretics at baseline were associated with hypokalemia. The combination of spironolactone and an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker was associated with incremental risk for hyperkalemia and protection from hypokalemia. Independent of region, both hypokalemia and hyperkalemia, were associated with higher risk for cardiovascular and all-cause mortality in multivariable-adjusted Cox regression models. CONCLUSIONS: Both hyperkalemia and hypokalemia are associated with heightened risk for mortality in HF-PEF. Use of spironolactone in this population requires careful laboratory surveillance of K+ and creatinine, particularly in high-risk groups.
Authors: Rajiv Agarwal; Amer Joseph; Stefan D Anker; Gerasimos Filippatos; Peter Rossing; Luis M Ruilope; Bertram Pitt; Peter Kolkhof; Charlie Scott; Robert Lawatscheck; Daniel J Wilson; George L Bakris Journal: J Am Soc Nephrol Date: 2021-11-03 Impact factor: 10.121
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Authors: Julian C Bachmann; Simon J Baumgart; Anna K Uryga; Markus H Bosteen; Giulia Borghetti; Michael Nyberg; Kate M Herum Journal: Cells Date: 2022-05-17 Impact factor: 7.666