Iris E Beldhuis1, Peder L Myhre2, Brian Claggett2, Kevin Damman3, James C Fang4, Eldrin F Lewis2, Eileen O'Meara5, Bertram Pitt6, Sanjiv J Shah7, Adriaan A Voors3, Marc A Pfeffer2, Scott D Solomon2, Akshay S Desai8. 1. 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. 2. Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 3. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 4. Division of Cardiovascular Medicine, University of Utah School of Medicine, Salt Lake City, Utah. 5. Department of Medicine, Montreal Heart Institute, Montreal, Montreal, Canada. 6. Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan. 7. Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 8. Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: adesai@bwh.harvard.edu.
Abstract
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.
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.
Authors: Mohammad Saud Khan; Muhammad Shahzeb Khan; Abdelmoniem Moustafa; Allen S Anderson; Rupal Mehta; Sadiya S Khan Journal: Am J Cardiol Date: 2019-11-19 Impact factor: 2.778
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Authors: Ravi B Patel; Gregg C Fonarow; Stephen J Greene; Shuaiqi Zhang; Brooke Alhanti; Adam D DeVore; Javed Butler; Paul A Heidenreich; Joanna C Huang; Michelle M Kittleson; Karen E Joynt Maddox; James J McDermott; Anjali Tiku Owens; Pamela N Peterson; Scott D Solomon; Orly Vardeny; Clyde W Yancy; Muthiah Vaduganathan Journal: J Am Coll Cardiol Date: 2021-05-11 Impact factor: 27.203
Authors: Edmund Ym Chung; Marinella Ruospo; Patrizia Natale; Davide Bolignano; Sankar D Navaneethan; Suetonia C Palmer; Giovanni Fm Strippoli Journal: Cochrane Database Syst Rev Date: 2020-10-27