Hanna Fröhlich1, Jingting Zhao1, Tobias Täger1, Rita Cebola1, Dieter Schellberg1, Hugo A Katus1, Morten Grundtvig1, Torstein Hole1, Dan Atar1, Stefan Agewall1, Lutz Frankenstein2. 1. From the Department of Cardiology, University of Heidelberg, Heidelberg, Germany (H.F., J.Z., T.T., R.C., D.S., L.F.); Medical Department, Innlandet Hospital Trust Division Lillehammer, Lillehammer, Norway (M.G.); Medical Faculty, Norwegian University of Science and Technology (NTNU), Trondheim, Norway (T.H.); Medical Clinic, Helse Møre and Romsdal HF, Ålesund, Norway (T.H.); and Department of Cardiology, Oslo University Hospital, Ulleval and Institute of Clinical Sciences, University of Oslo, Oslo, Norway (D.A., S.A.). 2. From the Department of Cardiology, University of Heidelberg, Heidelberg, Germany (H.F., J.Z., T.T., R.C., D.S., L.F.); Medical Department, Innlandet Hospital Trust Division Lillehammer, Lillehammer, Norway (M.G.); Medical Faculty, Norwegian University of Science and Technology (NTNU), Trondheim, Norway (T.H.); Medical Clinic, Helse Møre and Romsdal HF, Ålesund, Norway (T.H.); and Department of Cardiology, Oslo University Hospital, Ulleval and Institute of Clinical Sciences, University of Oslo, Oslo, Norway (D.A., S.A.). Lutz.Frankenstein@med.uni-heidelberg.de.
Abstract
BACKGROUND: β-Blockers exert a prognostic benefit in the treatment of chronic heart failure. Their pharmacological properties vary. The only substantial comparative trial to date-the Carvedilol or Metoprolol European Trial-has compared carvedilol with short-acting metoprolol tartrate at different dose equivalents. We therefore addressed the relative efficacy of equal doses of carvedilol and metoprolol succinate on survival in multicenter hospital outpatients with chronic heart failure. METHODS AND RESULTS: Four thousand sixteen patients with stable systolic chronic heart failure who were using eithercarvedilol or metoprolol succinatewere identified in the Norwegian Heart Failure Registry and The Heart Failure Registry of the University of Heidelberg, Germany. Patients were individually matched on both the dose equivalents and the respective propensity scores for β-blocker treatment. During a follow-up for 17 672 patient-years, it was found that 304 (27.2%) patients died in the carvedilol group and 1066 (36.8%) in the metoprolol group. In a univariable analysis of the general sample, metoprolol therapy was associated with higher mortality compared with carvedilol therapy (hazard ratio, 1.49; 95% confidence interval, 1.31-1.69; P<0.001). This difference was not seen after multivariable adjustment (hazard ratio, 0.93; 95% confidence interval, 0.57-1.50; P=0.75) and adjustment for propensity score and dose equivalents (hazard ratio, 1.06; 95% confidence interval, 0.94-1.20; P=0.36) or in the propensity and dose equivalent-matched sample (hazard ratio, 1.00; 95% confidence interval, 0.82-1.23; P=0.99). These results were essentially unchanged for all prespecified subgroups. CONCLUSIONS: In outpatients with chronic heart failure, no conclusive association between all-cause mortality and treatment with carvedilol or metoprolol succinate was observed after either multivariable adjustment or multilevel propensity score matching.
RCT Entities:
BACKGROUND: β-Blockers exert a prognostic benefit in the treatment of chronic heart failure. Their pharmacological properties vary. The only substantial comparative trial to date-the Carvedilol or Metoprolol European Trial-has compared carvedilol with short-acting metoprolol tartrate at different dose equivalents. We therefore addressed the relative efficacy of equal doses of carvedilol and metoprolol succinate on survival in multicenter hospital outpatients with chronic heart failure. METHODS AND RESULTS: Four thousand sixteen patients with stable systolic chronic heart failure who were using either carvedilol or metoprolol succinate were identified in the Norwegian Heart Failure Registry and The Heart Failure Registry of the University of Heidelberg, Germany. Patients were individually matched on both the dose equivalents and the respective propensity scores for β-blocker treatment. During a follow-up for 17 672 patient-years, it was found that 304 (27.2%) patients died in the carvedilol group and 1066 (36.8%) in the metoprolol group. In a univariable analysis of the general sample, metoprolol therapy was associated with higher mortality compared with carvedilol therapy (hazard ratio, 1.49; 95% confidence interval, 1.31-1.69; P<0.001). This difference was not seen after multivariable adjustment (hazard ratio, 0.93; 95% confidence interval, 0.57-1.50; P=0.75) and adjustment for propensity score and dose equivalents (hazard ratio, 1.06; 95% confidence interval, 0.94-1.20; P=0.36) or in the propensity and dose equivalent-matched sample (hazard ratio, 1.00; 95% confidence interval, 0.82-1.23; P=0.99). These results were essentially unchanged for all prespecified subgroups. CONCLUSIONS: In outpatients with chronic heart failure, no conclusive association between all-cause mortality and treatment with carvedilol or metoprolol succinate was observed after either multivariable adjustment or multilevel propensity score matching.
Authors: Hanna Fröhlich; Lorella Torres; Tobias Täger; Dieter Schellberg; Anna Corletto; Syed Kazmi; Kevin Goode; Morten Grundtvig; Torstein Hole; Hugo A Katus; John G F Cleland; Dan Atar; Andrew L Clark; Stefan Agewall; Lutz Frankenstein Journal: Clin Res Cardiol Date: 2017-04-22 Impact factor: 5.460
Authors: Brian Schwartz; Colin Pierce; Christian Madelaire; Morten Schou; Søren Lund Kristensen; Gunnar H Gislason; Lars Køber; Christian Torp-Pedersen; Charlotte Andersson Journal: J Am Heart Assoc Date: 2021-09-17 Impact factor: 5.501