TY - JOUR
T1 - Incident Hyperkalemia, Hypokalemia, and Clinical Outcomes During Spironolactone Treatment of Heart Failure With Preserved Ejection Fraction
T2 - Analysis of the TOPCAT Trial
AU - Desai, Akshay S.
AU - Liu, Jiankang
AU - Pfeffer, Marc A.
AU - Claggett, Brian
AU - Fleg, Jerome
AU - Lewis, Eldrin F.
AU - McKinlay, Sonja
AU - O'Meara, Eileen
AU - Shah, Sanjiv J.
AU - Sweitzer, Nancy K.
AU - Solomon, Scott
AU - Pitt, Bertram
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
KW - Hyperkalemia
KW - aldosterone
KW - diastolic heart failure
KW - heart failure
KW - hypokalemia
KW - mineralocorticoid receptor
KW - spironolactone
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UR - http://www.scopus.com/inward/citedby.url?scp=85046149615&partnerID=8YFLogxK
U2 - 10.1016/j.cardfail.2018.03.002
DO - 10.1016/j.cardfail.2018.03.002
M3 - Article
C2 - 29572190
AN - SCOPUS:85046149615
SN - 1071-9164
VL - 24
SP - 313
EP - 320
JO - Journal of cardiac failure
JF - Journal of cardiac failure
IS - 5
ER -