PMID- 30606484 OWN - NLM STAT- MEDLINE DCOM- 20200701 LR - 20200701 IS - 2213-1787 (Electronic) IS - 2213-1779 (Linking) VI - 7 IP - 1 DP - 2019 Jan TI - Efficacy and Safety of Spironolactone in Patients With HFpEF and Chronic Kidney Disease. PG - 25-32 LID - S2213-1779(18)30787-X [pii] LID - 10.1016/j.jchf.2018.10.017 [doi] AB - OBJECTIVES: This study investigated the association between baseline renal function and the net benefit of spironolactone in patients with heart failure (HF) with a preserved ejection fraction (HFpEF). BACKGROUND: Guidelines recommend consideration of spironolactone to reduce HF hospitalization in HFpEF. However, spironolactone may increase risk for hyperkalemia and worsening renal function, particularly in patients with chronic kidney disease. METHODS: This investigation analyzed data from patients enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) Americas study (N = 1,767) to examine the association between the baseline estimated glomerular filtration rate (eGFR) and the primary composite outcome of cardiovascular death, HF hospitalization, or aborted cardiac arrest, as well as safety outcomes, including hyperkalemia, worsening renal function, and permanent drug discontinuation for adverse events (AEs). Variations in the efficacy and safety of spironolactone according to eGFR were examined in Cox models using interaction terms. RESULTS: The incidence of both the primary outcome and drug-related AEs increased with declining eGFR. Compared with placebo, across all eGFR categories, spironolactone was associated with lower relative risk for the primary efficacy outcome and for hypokalemia, but higher relative risk for hyperkalemia, worsening renal function, and drug discontinuation. During 4-year follow-up, the absolute risk for AEs that prompted drug discontinuation was amplified in the lower eGFR categories, which suggested heightened risk for drug intolerance with declining renal function. CONCLUSIONS: Although consistent efficacy of spironolactone was observed across the range of eGFR, the risk of AEs was amplified in the lower eGFR categories. These data supported use of spironolactone to treat HFpEF patients with advanced chronic kidney disease only when close laboratory surveillance is possible. CI - Copyright (c) 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. FAU - Beldhuis, Iris E AU - Beldhuis IE AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. FAU - Myhre, Peder L AU - Myhre PL AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Claggett, Brian AU - Claggett B AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Damman, Kevin AU - Damman K AD - Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. FAU - Fang, James C AU - Fang JC AD - Division of Cardiovascular Medicine, University of Utah School of Medicine, Salt Lake City, Utah. FAU - Lewis, Eldrin F AU - Lewis EF AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - O'Meara, Eileen AU - O'Meara E AD - Department of Medicine, Montreal Heart Institute, Montreal, Montreal, Canada. FAU - Pitt, Bertram AU - Pitt B AD - Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan. FAU - Shah, Sanjiv J AU - Shah SJ AD - Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. FAU - Voors, Adriaan A AU - Voors AA AD - Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. FAU - Pfeffer, Marc A AU - Pfeffer MA AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Solomon, Scott D AU - Solomon SD AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Desai, Akshay S AU - Desai AS AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: adesai@bwh.harvard.edu. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - JACC Heart Fail JT - JACC. Heart failure JID - 101598241 RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 27O7W4T232 (Spironolactone) SB - IM CIN - JACC Heart Fail. 2019 Jan;7(1):33-35. PMID: 30606485 MH - Aged MH - Aged, 80 and over MH - Cardiovascular Diseases/mortality MH - Comorbidity MH - Deprescriptions MH - Disease Progression MH - Female MH - *Glomerular Filtration Rate MH - Heart Arrest/epidemiology MH - Heart Failure/*drug therapy/epidemiology/physiopathology MH - Hospitalization/statistics & numerical data MH - Humans MH - Hyperkalemia/chemically induced/epidemiology MH - Hypokalemia/chemically induced MH - Kaplan-Meier Estimate MH - Male MH - Middle Aged MH - Mineralocorticoid Receptor Antagonists/*therapeutic use MH - Proportional Hazards Models MH - Renal Insufficiency, Chronic/epidemiology/*metabolism MH - Severity of Illness Index MH - Spironolactone/*therapeutic use MH - *Stroke Volume MH - Treatment Outcome OTO - NOTNLM OT - chronic kidney disease OT - heart failure with preserved ejection fraction OT - renal function OT - safety OT - spironolactone EDAT- 2019/01/05 06:00 MHDA- 2020/07/02 06:00 CRDT- 2019/01/05 06:00 PHST- 2018/08/03 00:00 [received] PHST- 2018/10/16 00:00 [revised] PHST- 2018/10/23 00:00 [accepted] PHST- 2019/01/05 06:00 [entrez] PHST- 2019/01/05 06:00 [pubmed] PHST- 2020/07/02 06:00 [medline] AID - S2213-1779(18)30787-X [pii] AID - 10.1016/j.jchf.2018.10.017 [doi] PST - ppublish SO - JACC Heart Fail. 2019 Jan;7(1):25-32. doi: 10.1016/j.jchf.2018.10.017.