Marc A Pfeffer1, Brian Claggett2, Susan F Assmann2, Robin Boineau2, Inder S Anand2, Nadine Clausell2, Akshay S Desai2, Rafael Diaz2, Jerome L Fleg2, Ivan Gordeev2, John F Heitner2, Eldrin F Lewis2, Eileen O'Meara2, Jean-Lucien Rouleau2, Jeffrey L Probstfield2, Tamaz Shaburishvili2, Sanjiv J Shah2, Scott D Solomon2, Nancy K Sweitzer2, Sonja M McKinlay2, Bertram Pitt2. 1. From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (M.A.P., B.C., A.S.D., E.F.L., S.D.S.); New England Research Institutes, Inc, Watertown, MA (S.F.A., S.M.M.); National Heart, Lung, and Blood Institute, Bethesda, MD (R.B., J.L.F.); VA Medical Center and University of Minnesota, Minneapolis, MN (I.S.A.); Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil (N.C.); Estudios Clinicos Latinoamerica, Rosario, Argentina (R.D.); Pirogov Russian National Research Medical University, Moscow, Russia (I.G.); New York Methodist Hospital, Brooklyn, NY (J.F.H.); Montreal Heart Institute, Montreal, QC, Canada (E.O., J.L.R.); University of Washington Medical Center, Seattle (J.L.P.); Diagnostic Services Clinic, Tbilisi, Georgia (T.S.); Northwestern University, Chicago, IL (S.J.S.); University of Wisconsin, Madison (N.K.S.); and University of Michigan School of Medicine, Ann Arbor (B.P.). mpfeffer@rics.bwh.harvard.edu. 2. From the Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (M.A.P., B.C., A.S.D., E.F.L., S.D.S.); New England Research Institutes, Inc, Watertown, MA (S.F.A., S.M.M.); National Heart, Lung, and Blood Institute, Bethesda, MD (R.B., J.L.F.); VA Medical Center and University of Minnesota, Minneapolis, MN (I.S.A.); Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil (N.C.); Estudios Clinicos Latinoamerica, Rosario, Argentina (R.D.); Pirogov Russian National Research Medical University, Moscow, Russia (I.G.); New York Methodist Hospital, Brooklyn, NY (J.F.H.); Montreal Heart Institute, Montreal, QC, Canada (E.O., J.L.R.); University of Washington Medical Center, Seattle (J.L.P.); Diagnostic Services Clinic, Tbilisi, Georgia (T.S.); Northwestern University, Chicago, IL (S.J.S.); University of Wisconsin, Madison (N.K.S.); and University of Michigan School of Medicine, Ann Arbor (B.P.).
Abstract
BACKGROUND: Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) patients with heart failure and preserved left ventricular ejection fraction assigned tospironolactone did not achieve a significant reduction in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalization for management of heart failure) compared with patients receiving placebo. In a post hoc analysis, an ≈4-fold difference was identified in this composite event rate between the 1678 patients randomized from Russia and Georgia compared with the 1767 enrolled from the United States, Canada, Brazil, and Argentina (the Americas). METHODS AND RESULTS: To better understand this regional difference in clinical outcomes, demographic characteristics of these populations and their responses to spironolactone were explored. Patients from Russia/Georgia were younger, had less atrial fibrillation and diabetes mellitus, but were more likely to have had prior myocardial infarction or a hospitalization for heart failure. Russia/Georgia patients also had lower left ventricular ejection fraction and creatinine but higher diastolic blood pressure (all P<0.001). Hyperkalemia and doubling of creatinine were more likely and hypokalemia was less likely in patients receiving spironolactone in the Americas with no significant treatment effects in Russia/Georgia. All clinical event rates were markedly lower in Russia/Georgia, and there was no detectable impact of spironolactone on any outcomes. In contrast, in the Americas, the rates of the primary outcome, cardiovascular death, and hospitalization for heart failure were significantly reduced by spironolactone. CONCLUSIONS: This post hoc analysis demonstrated greater potassium and creatinine changes and possible clinical benefits with spironolactone in patients with heart failure and preserved ejection fraction from the Americas. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.
RCT Entities:
BACKGROUND: Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) patients with heart failure and preserved left ventricular ejection fraction assigned to spironolactone did not achieve a significant reduction in the primary composite outcome (time to cardiovascular death, aborted cardiac arrest, or hospitalization for management of heart failure) compared with patients receiving placebo. In a post hoc analysis, an ≈4-fold difference was identified in this composite event rate between the 1678 patients randomized from Russia and Georgia compared with the 1767 enrolled from the United States, Canada, Brazil, and Argentina (the Americas). METHODS AND RESULTS: To better understand this regional difference in clinical outcomes, demographic characteristics of these populations and their responses to spironolactone were explored. Patients from Russia/Georgia were younger, had less atrial fibrillation and diabetes mellitus, but were more likely to have had prior myocardial infarction or a hospitalization for heart failure. Russia/Georgiapatients also had lower left ventricular ejection fraction and creatinine but higher diastolic blood pressure (all P<0.001). Hyperkalemia and doubling of creatinine were more likely and hypokalemia was less likely in patients receiving spironolactone in the Americas with no significant treatment effects in Russia/Georgia. All clinical event rates were markedly lower in Russia/Georgia, and there was no detectable impact of spironolactone on any outcomes. In contrast, in the Americas, the rates of the primary outcome, cardiovascular death, and hospitalization for heart failure were significantly reduced by spironolactone. CONCLUSIONS: This post hoc analysis demonstrated greater potassium and creatinine changes and possible clinical benefits with spironolactone in patients with heart failure and preserved ejection fraction from the Americas. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.
Authors: Jennifer E Ho; Emily K Zern; Luke Wooster; Cole S Bailey; Thomas Cunningham; Aaron S Eisman; Kathryn M Hardin; Giovanna A Zampierollo; Petr Jarolim; Paul P Pappagianopoulos; Rajeev Malhotra; Matthew Nayor; Gregory D Lewis Journal: Circulation Date: 2019-05-28 Impact factor: 29.690
Authors: Javed Butler; Adrian F Hernandez; Kevin J Anstrom; Andreas Kalogeropoulos; Margaret M Redfield; Marvin A Konstam; W H Wilson Tang; G Michael Felker; Monica R Shah; Eugene Braunwald Journal: JACC Heart Fail Date: 2016-08-10 Impact factor: 12.035
Authors: Peder Langeland Myhre; Muthiah Vaduganathan; Brian L Claggett; Inder S Anand; Nancy K Sweitzer; James C Fang; Eileen O'Meara; Sanjiv J Shah; Akshay S Desai; Eldrin F Lewis; Jean Rouleau; Bertram Pitt; Marc A Pfeffer; Scott D Solomon Journal: JAMA Cardiol Date: 2018-10-01 Impact factor: 14.676