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Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)

Item Type:Article
Title:Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)
Creators Name:Hjalmarson, A. and Goldstein, S. and Fagerberg, B. and Wedel, H. and Waagstein, F. and Kjekshus, J. and Wikstrand, J. and Hassle, A. and Westergren, G. and Hassle, A. and Thimell, M. and El Allaf, D. and Vitovec, J. and Aldershvile, J. and Halinen, M. and Dietz, R. and Neuhaus, K.L. and Janosi, A. and Thorgeirsson, G. and Dunselman, P. and Gullestad, L. and Kuch, J. and Herlitz, J. and Rickenbacher, P. and Ball, S. and Gottlieb, S. and Deedwania, P. and Vandenhoven, G. and Novakova, I. and Danker, S. and Lundstroem, M. and Meyer-Sabellek, W. and Balla, I. and Sveinsdottir, M. and Dorhout, B. and Hildebrandt, A. and Szczurko, I. and Larsson, C. and Bucher, E. and Scott, E. and Dwyer, D. and Julian, D.G. and DeMets, D.L. and Chatterjee, K. and Feyzi, J. and Lehto, S. and Karpati, P. and Motz, W. and Samuelsson, O. and Viersma, J.W. and Andersson, B. and Berthe, C. and Boutefeu, J.M. and Boxho, G. and Decroly, P. and Derbaudrenghien, J.P. and El Allaf, D. and Pirlet, J. and Henry, P. and Heyndrickx, G. and Missault, L. and Nannan, M. and Timmermans, P. and Vachiery, J.L. and Van Mieghem, W. and Vandenbossche, J.L. and Dvorak, K. and Herold, M. and Hradec, J. and Kana, A. and Petr, P. and Rybka, J. and Smid, J. and Svitil, P. and Toman, J. and Vitovec, J. and Agner, E. and Aldershvile, J. and Amtorp, O. and Egstrup, K. and Eliasen, P. and Gotzsche, C.O. and Hildebrandt, P. and Johannesen, A. and Kaiser-Nielsen, P. and Nielsen, H. and Nielsen, P.E. and Pedersen, F. and Nielsen, J.R. and Skagen, K. and Halinen, M. and Honkanen, T. and Hussi, E. and Juvonen, J. and Jaeaeskelaeinen, H. and Rinne, J. and Salonen, T. and Andresen, D. and Berwing, H. and Dietz, R. and Forster, A. and Hauf, G.F. and Krosse, B. and Luderitz, B. and von Olshausen, K.E. and Schmailzl, K.J.G. and Schwimmbeck, P.L. and Sigmund, M. and Voller, H. and Czuriga, I. and Hetey, M. and Janosi, A. and Katona, A. and Lengyel, M. and Nyaradi, A. and Rednik, A. and Sandori, K. and Szabo, P. and Tarjan, J. and Tenczer, J. and Timar, S. and Valyi, P. and Veress, G. and Zamolyi, K. and Oze, B. and Thorgeirsson, G. and Thorgeirsson, G. and Bernink, P.J.L.M. and Bredero, A.C. and Breedveld, R.W. and Breuls, P.N.W.M. and Bucx, J.J.J. and Cornel, J.H. and De Milliano, P.A.R. and Dunselman, P.H.J.M. and Hamer, B.J.B. and Holwerda, N.L. and Hoogsteen, J. and Hoorntje, J.C.A. and Kragten, J.A. and Liem, A.H. and Linssen, G.C.M. and Michels, H.R. and Misier, A.R.R. and Schaafsma, H.J. and Sijbring, P. and Taverne, R.J.T. and Van Kempen, L.H.J. and Van Stralen, R. and Van Veldhuisen, P.J. and Veerhoek, M.J. and Werter, C.J.P.J. and Wesdorp, J.C.L. and Willems, A.R. and Withagen, A.J.A.M. and Zwart, P.A.G. and Bjornerheim, R. and Dahle, M. and Dickstein, K. and Froland, G.S. and Gullestad, L. and Gundersen, T. and Hofsoy, K. and Hole, T.L. and Johansen, T. and Mannsverk, J. and Nesje, P. and Omland, T.M. and Sjodin, C. and Smith, P. and Tjonndal, H.A. and Vikesdal, O. and Waage, K. and Jaworska, K. and Kolodziej, P. and Kornacewicz-Jach, Z. and Krzeminska-Pakula, M. and Kuch, J. and Piotrowski, J.W. and Piwowarska, W. and Stogowski, A. and Wodniecki, J. and Wrabec, K. and Ahlstrom, P. and Ekdahl, S. and Hemmingson, L.O. and Herlitz, J. and Holmberg, L. and Lernfelt, B. and Nilsson, H. and Widgren, B. and Angman, K. and Erne, P. and Mohacsi, P. and Polikar, R. and Rickenbacher, P. and Schlapfer, H. and Batin, P. and Berkin, K.E. and Callaghan, T.S. and Forfar, J. and Frenneaux, M. and Greenbaum, R.A. and Maltz, M. and Murdoch, D. and Reynolds, G. and Stephens, J. and Struthers, A. and Swan, J. and Tildesley, G. and Abbasi, A. and Alagona, P. and Alderman, J. and Alipour, M. and Anderson, J.L. and Ansari, Z. and Ashraf, M. and Beanblossom, B.T. and Bennett, S. and Benvenuti, D. and Berk, M.R. and Bhalla, R. and Bilazarian, S.D. and Browne, K.F. and Buchter, C.M. and Carlson, R. and Carlson, C.J. and Danisa, K. and Dauber, I. and DeWood, M.A. and Deedwania, P. and Dennish, G. and Denny, D.M. and DiBianco, R. and Diller, P.M. and Dunlap, M. and Dowd, K. and Edmiston, A. and El Shahawy, M. and Elkayam, U. and Farnham, J. and Fenster, P. and Friedman, S. and Heywood, T. and Galichia, J.P. and Geller, M. and Ghali, J.K. and Gheorghiade, M.
Abstract:BACKGROUND: Metoprolol can improve haemodynamics in chronic heart failure, but survival benefit has not been proven. We investigated whether metoprolol controlled release/extended release (CR/XL) once daily, in addition to standard therapy, would lower mortality in patients with decreased ejection fraction and symptoms of heart failure. METHODS: We enrolled 3991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with ejection fraction of 0.40 or less, stabilised with optimum standard therapy, in a double-blind randomised controlled study. Randomisation was preceded by a 2-week single-blind placebo run-in period. 1990 patients were randomly assigned metoprolol CR/XL 12.5 mg (NYHA III-IV) or 25.0 mg once daily (NYHA II) and 2001 were assigned placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analysed by intention to treat. FINDINGS: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in the metoprolol CR/XL group than in the placebo group (145 [7.2%, per patient-year of follow-up]) vs 217 deaths [11.0%], relative risk 0.66 [95% CI 0.53-0.81]; p=0.00009 or adjusted for interim analyses p=0.0062). There were fewer sudden deaths in the metoprolol CR/XL group than in the placebo group (79 vs 132, 0.59 [0.45-0.78]; p=0.0002) and deaths from worsening heart failure (30 vs 58, 0.51 [0.33-0.79]; p=0.0023). INTERPRETATION: Metoprolol CR/XL once daily in addition to optimum standard therapy improved survival. The drug was well tolerated.
Keywords:Cardiovascular Diseases, Sudden Death, Delayed-Action Preparations, Double-Blind Method, Heart Failure, Metoprolol, Survival Rate
Page Range:2001-2007
Date:12 June 1999
Official Publication:https://doi.org/10.1016/S0140-6736(99)04440-2
PubMed:View item in PubMed

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