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

A. Hjalmarson, S. Goldstein, B. Fagerberg, H. Wedel, F. Waagstein, J. Kjekshus, J. Wikstrand, G. Westergren, M. Thimell, D. El Allaf, J. Vítovec, J. Aldershvile, M. Halinen, R. Dietz, K. L. Neuhaus, A. Jánosi, G. Thorgeirsson, P. Dunselman, L. Gullestad, J. KuchJ. Herlitz, P. Rickenbacher, S. Ball, S. Gottlieb, P. Deedwania, G. Vandenhoven, I. Nováková, S. Danker, M. Lundström, W. Meyer-Sabellek, I. Balla, M. Sveinsdottir, B. Dorhout, A. Hildebrandt, I. Szczurko, C. Larsson, E. Bucher, E. Scott, D. Dwyer, D. G. Julian, D. L. DeMets, K. Chatterjee, J. Feyzi, S. Lehto, P. Kárpáti, W. Motz, O. Samuelsson, J. W. Viersma, B. Andersson, C. Berthe, J. M. Boutefeu, G. Boxho, P. Decroly, J. P. Derbaudrenghien, J. Pirlet, P. Henry, G. Heyndrickx, L. Missault, M. Nannan, P. Timmermans, J. L. Vachiery, W. Van Mieghem, J. L. Vandenbossche, K. Dvorák, M. Herold, J. Hradec, A. Kána, P. Petr, J. Rybka, J. Smíd, P. Svítil, J. Toman, E. Agner, O. Amtorp, K. Egstrup, P. Eliasen, C. O. Gotzsche, P. Hildebrandt, A. Johannesen, P. Kaiser-Nielsen, H. Nielsen, P. E. Nielsen, F. Pedersen, J. Rokkedal Nielsen, K. Skagen, T. Honkanen, E. Hussi, J. Juvonen, H. Jääskeläinen, J. Rinne, T. Salonen, D. Andresen, H. Berwing, [No Value] Bethge, [No Value] Beythien, [No Value] Bischoff, [No Value] Bundschu, [No Value] Daniel, [No Value] Darius, [No Value] Delius, [No Value] Drude, [No Value] Dingerkus, [No Value] Dück, [No Value] Eichler, [No Value] Fach, A. Förster, [No Value] Girth, [No Value] Goss, [No Value] Hahn, [No Value] Hambrecht, G. F. Hauf, [No Value] Heinemann, [No Value] Hepp, [No Value] Janka, [No Value] Klocke, [No Value] Konz, B. Krosse, [No Value] Kühlkamp, [No Value] Lewek, B. Lüderitz, [No Value] Löbe, [No Value] Maier, [No Value] Melchior, [No Value] Müller, [No Value] Mäurer, [No Value] Nast, [No Value] Neuhaus, [No Value] Obst, [No Value] Odemar, K. E. von Olshausen, [No Value] Pomykaj, K. J G Schmailzl, [No Value] Schrader, [No Value] Schröder, P. L. Schwimmbeck, M. Sigmund, [No Value] Simon, [No Value] Strasser, [No Value] Thilo, [No Value] Vöhringer, H. Völler, [No Value] Weibrodt, [No Value] Wirtz, [No Value] Wunderlich, I. Czuriga, M. Hetey, A. Katona, M. Lengyel, A. Nyárádi, A. Rednik, K. Sándori, P. Szabó, J. Tarján, J. Tenczer, S. Timár, P. Vályi, G. Veress, K. Zámolyi, B. Öze, Ge Thorgeirsson, Gu Thorgeirsson, P. J L M Bernink, A. C. Bredero, R. W. Breedveld, P. N W M Breuls, J. J J Bucx, J. H. Cornel, P. A R De Milliano, P. H J M Dunselman, B. J B Hamer, N. L. Holwerda, J. Hoogsteen, J. C A Hoorntje, J. A. Kragten, A. H. Liem, G. C M Linssen, H. R. Michels, A. R. Ramdat Misier, H. J. Schaafsma, P. Sijbring, R. J T Taverne, L. H J Van Kempen, R. Van Stralen, P. J. Van Veldhuisen, M. J. Veerhoek, C. J P J Werter, J. C L Wesdorp, A. R. Willems, A. J A M Withagen, P. A G Zwart, R. Bjornerheim, M. Dahle, K. Dickstein, G. S. Froland, T. Gundersen, K. Hofsoy, T. L. Hole, T. Johansen, J. Mannsverk, P. Nesje, T. M. Omland, C. Sjödin, P. Smith, H. A. Tjonndal, O. Vikesdal, K. Waage, [No Value] Adamus, K. Jaworska, P. Kolodziej, Z. Kornacewicz-Jach, M. Krzemiñska-Pakula, J. W. Piotrowski, W. Piwowarska, A. Stogowski, J. Wodniecki, K. Wrabec, P. Ahlström, S. Ekdahl, L. O. Hemmingson, L. Holmberg, B. Lernfelt, H. Nilsson B Widgren, K. Ångman, P. Erne, P. Mohacsi, R. Polikar, H. Schläpfer, P. Batin, K. E. Berkin, T. S. Callaghan, J. Forfar, M. Frenneaux, R. A. Greenbaum, M. Maltz, D. Murdoch, G. Reynolds, J. Stephens, A. Struthers, J. Swan, G. Tildesley, A. Abbasi, P. Alagona, J. Alderman, M. Alipour, J. L. Anderson, Z. Ansari, M. Ashraf, B. T. Beanblossom, S. Bennett, D. Benvenuti, M. R. Berk, R. Bhalla, S. D. Bilazarian, K. F. Browne, C. MBuchter, R. Carlson, C. J. Carlson, K. Danisa, I. Dauber, M. A. DeWood, G. Dennish, D. M. Denny, R. DiBianco, P. M. Diller, M. Dunlap, K. Dowd, A. Edmiston, M. El Shahawy, U. Elkayam, J. Farnham, P. Fenster, S. Friedman, T. Heywood, J. P. Galichia, M. Geller, J. K. Ghali, M. Gheorghiade, T. Giles, R. Gillespe, G. Goldberg, M. C. Goldberg, D. A. Goldscher, G. P. Gooden, M. Goodman, L. Goodman, J. Gorwit, S. S. Gottlieb, A. Gradman, D. Grech, T. Hack, J. H. Hall, M. T. Hattenhauer, M. B. Higginbotham, S. Hutchins, M. Imburgia, B. J. Iteld, B. Jackson, S. Jafri, W. Jauch, S. Jennison, B. H. Kahn, W. Kao, K. Kaplan, R. Karlsberg, H. L. Kennedy, J. J. Kennedy, L. Kirkegaard, D. H. Kraus, K. LaBresh, L. Lalonde, M. F. Lesser, R. Levites, M. Levy, R. K. Lewis, I. K. Loh, H. Madyoon, F. Maislos, D. Mann, G. L. Maurice, A. Nisar, W. Old, J. D. Pappas, K. Phadke, S. Promisloff, A. M. Rashkow, B. Reeves, J. H. Rosen, M. Rotman, T. Saleem, S. V. Savran, R. Shah, Y. Shalev, J. G. Shanes, M. O'Shaughnessy, B. Silverman, R. M. Steingart, L. Swenson, K. Syed, U. Thadani, R. D. Thorsen, M. J. Tonkon, R. Touchon, G. Uhl, K. J. Vaska, S. G. Wagner, C. J. Weaver, R. J. Weiss, W. J. Wickemeyer, H. J. Willens, J. R. Wilson, R. Wright, L. Yellen

Research output: Contribution to journalArticle

3910 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2001-2007
Number of pages7
JournalLancet
Volume353
Issue number9169
DOIs
StatePublished - Jun 12 1999
Externally publishedYes

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Metoprolol
Heart Failure
Placebos
Mortality
Survival
Random Allocation
Sudden Death
Therapeutics
Hemodynamics
Safety
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hjalmarson, A., Goldstein, S., Fagerberg, B., Wedel, H., Waagstein, F., Kjekshus, J., ... Yellen, L. (1999). Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet, 353(9169), 2001-2007. https://doi.org/10.1016/S0140-6736(99)04440-2

Effect of metoprolol CR/XL in chronic heart failure : Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). / Hjalmarson, A.; Goldstein, S.; Fagerberg, B.; Wedel, H.; Waagstein, F.; Kjekshus, J.; Wikstrand, J.; Westergren, G.; Thimell, M.; El Allaf, D.; Vítovec, J.; Aldershvile, J.; Halinen, M.; Dietz, R.; Neuhaus, K. L.; Jánosi, A.; Thorgeirsson, G.; Dunselman, P.; Gullestad, L.; Kuch, J.; Herlitz, J.; Rickenbacher, P.; Ball, S.; Gottlieb, S.; Deedwania, P.; Vandenhoven, G.; Nováková, I.; Danker, S.; Lundström, M.; Meyer-Sabellek, W.; Balla, I.; Sveinsdottir, M.; Dorhout, B.; Hildebrandt, A.; Szczurko, I.; Larsson, C.; Bucher, E.; Scott, E.; Dwyer, D.; Julian, D. G.; DeMets, D. L.; Chatterjee, K.; Feyzi, J.; Lehto, S.; Kárpáti, P.; Motz, W.; Samuelsson, O.; Viersma, J. W.; Andersson, B.; Berthe, C.; Boutefeu, J. M.; Boxho, G.; Decroly, P.; Derbaudrenghien, J. P.; Pirlet, J.; Henry, P.; Heyndrickx, G.; Missault, L.; Nannan, M.; Timmermans, P.; Vachiery, J. L.; Van Mieghem, W.; Vandenbossche, J. L.; Dvorák, K.; Herold, M.; Hradec, J.; Kána, A.; Petr, P.; Rybka, J.; Smíd, J.; Svítil, P.; Toman, J.; Agner, E.; Amtorp, O.; Egstrup, K.; Eliasen, P.; Gotzsche, C. O.; Hildebrandt, P.; Johannesen, A.; Kaiser-Nielsen, P.; Nielsen, H.; Nielsen, P. E.; Pedersen, F.; Rokkedal Nielsen, J.; Skagen, K.; Honkanen, T.; Hussi, E.; Juvonen, J.; Jääskeläinen, H.; Rinne, J.; Salonen, T.; Andresen, D.; Berwing, H.; Bethge, [No Value]; Beythien, [No Value]; Bischoff, [No Value]; Bundschu, [No Value]; Daniel, [No Value]; Darius, [No Value]; Delius, [No Value]; Drude, [No Value]; Dingerkus, [No Value]; Dück, [No Value]; Eichler, [No Value]; Fach, [No Value]; Förster, A.; Girth, [No Value]; Goss, [No Value]; Hahn, [No Value]; Hambrecht, [No Value]; Hauf, G. F.; Heinemann, [No Value]; Hepp, [No Value]; Janka, [No Value]; Klocke, [No Value]; Konz, [No Value]; Krosse, B.; Kühlkamp, [No Value]; Lewek, [No Value]; Lüderitz, B.; Löbe, [No Value]; Maier, [No Value]; Melchior, [No Value]; Müller, [No Value]; Mäurer, [No Value]; Nast, [No Value]; Neuhaus, [No Value]; Obst, [No Value]; Odemar, [No Value]; von Olshausen, K. E.; Pomykaj, [No Value]; Schmailzl, K. J G; Schrader, [No Value]; Schröder, [No Value]; Schwimmbeck, P. L.; Sigmund, M.; Simon, [No Value]; Strasser, [No Value]; Thilo, [No Value]; Vöhringer, [No Value]; Völler, H.; Weibrodt, [No Value]; Wirtz, [No Value]; Wunderlich, [No Value]; Czuriga, I.; Hetey, M.; Katona, A.; Lengyel, M.; Nyárádi, A.; Rednik, A.; Sándori, K.; Szabó, P.; Tarján, J.; Tenczer, J.; Timár, S.; Vályi, P.; Veress, G.; Zámolyi, K.; Öze, B.; Thorgeirsson, Ge; Thorgeirsson, Gu; Bernink, P. J L M; Bredero, A. C.; Breedveld, R. W.; Breuls, P. N W M; Bucx, J. J J; Cornel, J. H.; De Milliano, P. A R; Dunselman, P. H J M; Hamer, B. J B; Holwerda, N. L.; Hoogsteen, J.; Hoorntje, J. C A; Kragten, J. A.; Liem, A. H.; Linssen, G. C M; Michels, H. R.; Ramdat Misier, A. R.; Schaafsma, H. J.; Sijbring, P.; Taverne, R. J T; Van Kempen, L. H J; Van Stralen, R.; Van Veldhuisen, P. J.; Veerhoek, M. J.; Werter, C. J P J; Wesdorp, J. C L; Willems, A. R.; Withagen, A. J A M; Zwart, P. A G; Bjornerheim, R.; Dahle, M.; Dickstein, K.; Froland, G. S.; Gundersen, T.; Hofsoy, K.; Hole, T. L.; Johansen, T.; Mannsverk, J.; Nesje, P.; Omland, T. M.; Sjödin, C.; Smith, P.; Tjonndal, H. A.; Vikesdal, O.; Waage, K.; Adamus, [No Value]; Jaworska, K.; Kolodziej, P.; Kornacewicz-Jach, Z.; Krzemiñska-Pakula, M.; Piotrowski, J. W.; Piwowarska, W.; Stogowski, A.; Wodniecki, J.; Wrabec, K.; Ahlström, P.; Ekdahl, S.; Hemmingson, L. O.; Holmberg, L.; Lernfelt, B.; Nilsson B Widgren, H.; Ångman, K.; Erne, P.; Mohacsi, P.; Polikar, R.; Schläpfer, H.; Batin, P.; Berkin, K. E.; Callaghan, T. S.; Forfar, J.; Frenneaux, M.; Greenbaum, R. A.; Maltz, M.; Murdoch, D.; Reynolds, G.; Stephens, J.; Struthers, A.; Swan, J.; Tildesley, G.; Abbasi, A.; Alagona, P.; Alderman, J.; Alipour, M.; Anderson, J. L.; Ansari, Z.; Ashraf, M.; Beanblossom, B. T.; Bennett, S.; Benvenuti, D.; Berk, M. R.; Bhalla, R.; Bilazarian, S. D.; Browne, K. F.; MBuchter, C.; Carlson, R.; Carlson, C. J.; Danisa, K.; Dauber, I.; DeWood, M. A.; Dennish, G.; Denny, D. M.; DiBianco, R.; Diller, P. M.; Dunlap, M.; Dowd, K.; Edmiston, A.; El Shahawy, M.; Elkayam, U.; Farnham, J.; Fenster, P.; Friedman, S.; Heywood, T.; Galichia, J. P.; Geller, M.; Ghali, J. K.; Gheorghiade, M.; Giles, T.; Gillespe, R.; Goldberg, G.; Goldberg, M. C.; Goldscher, D. A.; Gooden, G. P.; Goodman, M.; Goodman, L.; Gorwit, J.; Gottlieb, S. S.; Gradman, A.; Grech, D.; Hack, T.; Hall, J. H.; Hattenhauer, M. T.; Higginbotham, M. B.; Hutchins, S.; Imburgia, M.; Iteld, B. J.; Jackson, B.; Jafri, S.; Jauch, W.; Jennison, S.; Kahn, B. H.; Kao, W.; Kaplan, K.; Karlsberg, R.; Kennedy, H. L.; Kennedy, J. J.; Kirkegaard, L.; Kraus, D. H.; LaBresh, K.; Lalonde, L.; Lesser, M. F.; Levites, R.; Levy, M.; Lewis, R. K.; Loh, I. K.; Madyoon, H.; Maislos, F.; Mann, D.; Maurice, G. L.; Nisar, A.; Old, W.; Pappas, J. D.; Phadke, K.; Promisloff, S.; Rashkow, A. M.; Reeves, B.; Rosen, J. H.; Rotman, M.; Saleem, T.; Savran, S. V.; Shah, R.; Shalev, Y.; Shanes, J. G.; O'Shaughnessy, M.; Silverman, B.; Steingart, R. M.; Swenson, L.; Syed, K.; Thadani, U.; Thorsen, R. D.; Tonkon, M. J.; Touchon, R.; Uhl, G.; Vaska, K. J.; Wagner, S. G.; Weaver, C. J.; Weiss, R. J.; Wickemeyer, W. J.; Willens, H. J.; Wilson, J. R.; Wright, R.; Yellen, L.

In: Lancet, Vol. 353, No. 9169, 12.06.1999, p. 2001-2007.

Research output: Contribution to journalArticle

Hjalmarson, A, Goldstein, S, Fagerberg, B, Wedel, H, Waagstein, F, Kjekshus, J, Wikstrand, J, Westergren, G, Thimell, M, El Allaf, D, Vítovec, J, Aldershvile, J, Halinen, M, Dietz, R, Neuhaus, KL, Jánosi, A, Thorgeirsson, G, Dunselman, P, Gullestad, L, Kuch, J, Herlitz, J, Rickenbacher, P, Ball, S, Gottlieb, S, Deedwania, P, Vandenhoven, G, Nováková, I, Danker, S, Lundström, M, Meyer-Sabellek, W, Balla, I, Sveinsdottir, M, Dorhout, B, Hildebrandt, A, Szczurko, I, Larsson, C, Bucher, E, Scott, E, Dwyer, D, Julian, DG, DeMets, DL, Chatterjee, K, Feyzi, J, Lehto, S, Kárpáti, P, Motz, W, Samuelsson, O, Viersma, JW, Andersson, B, Berthe, C, Boutefeu, JM, Boxho, G, Decroly, P, Derbaudrenghien, JP, Pirlet, J, Henry, P, Heyndrickx, G, Missault, L, Nannan, M, Timmermans, P, Vachiery, JL, Van Mieghem, W, Vandenbossche, JL, Dvorák, K, Herold, M, Hradec, J, Kána, A, Petr, P, Rybka, J, Smíd, J, Svítil, P, Toman, J, Agner, E, Amtorp, O, Egstrup, K, Eliasen, P, Gotzsche, CO, Hildebrandt, P, Johannesen, A, Kaiser-Nielsen, P, Nielsen, H, Nielsen, PE, Pedersen, F, Rokkedal Nielsen, J, Skagen, K, Honkanen, T, Hussi, E, Juvonen, J, Jääskeläinen, H, Rinne, J, Salonen, T, Andresen, D, Berwing, H, Bethge, NV, Beythien, NV, Bischoff, NV, Bundschu, NV, Daniel, NV, Darius, NV, Delius, NV, Drude, NV, Dingerkus, NV, Dück, NV, Eichler, NV, Fach, NV, Förster, A, Girth, NV, Goss, NV, Hahn, NV, Hambrecht, NV, Hauf, GF, Heinemann, NV, Hepp, NV, Janka, NV, Klocke, NV, Konz, NV, Krosse, B, Kühlkamp, NV, Lewek, NV, Lüderitz, B, Löbe, NV, Maier, NV, Melchior, NV, Müller, NV, Mäurer, NV, Nast, NV, Neuhaus, NV, Obst, NV, Odemar, NV, von Olshausen, KE, Pomykaj, NV, Schmailzl, KJG, Schrader, NV, Schröder, NV, Schwimmbeck, PL, Sigmund, M, Simon, NV, Strasser, NV, Thilo, NV, Vöhringer, NV, Völler, H, Weibrodt, NV, Wirtz, NV, Wunderlich, NV, Czuriga, I, Hetey, M, Katona, A, Lengyel, M, Nyárádi, A, Rednik, A, Sándori, K, Szabó, P, Tarján, J, Tenczer, J, Timár, S, Vályi, P, Veress, G, Zámolyi, K, Öze, B, Thorgeirsson, G, Thorgeirsson, G, Bernink, PJLM, Bredero, AC, Breedveld, RW, Breuls, PNWM, Bucx, JJJ, Cornel, JH, De Milliano, PAR, Dunselman, PHJM, Hamer, BJB, Holwerda, NL, Hoogsteen, J, Hoorntje, JCA, Kragten, JA, Liem, AH, Linssen, GCM, Michels, HR, Ramdat Misier, AR, Schaafsma, HJ, Sijbring, P, Taverne, RJT, Van Kempen, LHJ, Van Stralen, R, Van Veldhuisen, PJ, Veerhoek, MJ, Werter, CJPJ, Wesdorp, JCL, Willems, AR, Withagen, AJAM, Zwart, PAG, Bjornerheim, R, Dahle, M, Dickstein, K, Froland, GS, Gundersen, T, Hofsoy, K, Hole, TL, Johansen, T, Mannsverk, J, Nesje, P, Omland, TM, Sjödin, C, Smith, P, Tjonndal, HA, Vikesdal, O, Waage, K, Adamus, NV, Jaworska, K, Kolodziej, P, Kornacewicz-Jach, Z, Krzemiñska-Pakula, M, Piotrowski, JW, Piwowarska, W, Stogowski, A, Wodniecki, J, Wrabec, K, Ahlström, P, Ekdahl, S, Hemmingson, LO, Holmberg, L, Lernfelt, B, Nilsson B Widgren, H, Ångman, K, Erne, P, Mohacsi, P, Polikar, R, Schläpfer, H, Batin, P, Berkin, KE, Callaghan, TS, Forfar, J, Frenneaux, M, Greenbaum, RA, Maltz, M, Murdoch, D, Reynolds, G, Stephens, J, Struthers, A, Swan, J, Tildesley, G, Abbasi, A, Alagona, P, Alderman, J, Alipour, M, Anderson, JL, Ansari, Z, Ashraf, M, Beanblossom, BT, Bennett, S, Benvenuti, D, Berk, MR, Bhalla, R, Bilazarian, SD, Browne, KF, MBuchter, C, Carlson, R, Carlson, CJ, Danisa, K, Dauber, I, DeWood, MA, Dennish, G, Denny, DM, DiBianco, R, Diller, PM, Dunlap, M, Dowd, K, Edmiston, A, El Shahawy, M, Elkayam, U, Farnham, J, Fenster, P, Friedman, S, Heywood, T, Galichia, JP, Geller, M, Ghali, JK, Gheorghiade, M, Giles, T, Gillespe, R, Goldberg, G, Goldberg, MC, Goldscher, DA, Gooden, GP, Goodman, M, Goodman, L, Gorwit, J, Gottlieb, SS, Gradman, A, Grech, D, Hack, T, Hall, JH, Hattenhauer, MT, Higginbotham, MB, Hutchins, S, Imburgia, M, Iteld, BJ, Jackson, B, Jafri, S, Jauch, W, Jennison, S, Kahn, BH, Kao, W, Kaplan, K, Karlsberg, R, Kennedy, HL, Kennedy, JJ, Kirkegaard, L, Kraus, DH, LaBresh, K, Lalonde, L, Lesser, MF, Levites, R, Levy, M, Lewis, RK, Loh, IK, Madyoon, H, Maislos, F, Mann, D, Maurice, GL, Nisar, A, Old, W, Pappas, JD, Phadke, K, Promisloff, S, Rashkow, AM, Reeves, B, Rosen, JH, Rotman, M, Saleem, T, Savran, SV, Shah, R, Shalev, Y, Shanes, JG, O'Shaughnessy, M, Silverman, B, Steingart, RM, Swenson, L, Syed, K, Thadani, U, Thorsen, RD, Tonkon, MJ, Touchon, R, Uhl, G, Vaska, KJ, Wagner, SG, Weaver, CJ, Weiss, RJ, Wickemeyer, WJ, Willens, HJ, Wilson, JR, Wright, R & Yellen, L 1999, 'Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)', Lancet, vol. 353, no. 9169, pp. 2001-2007. https://doi.org/10.1016/S0140-6736(99)04440-2
Hjalmarson, A. ; Goldstein, S. ; Fagerberg, B. ; Wedel, H. ; Waagstein, F. ; Kjekshus, J. ; Wikstrand, J. ; Westergren, G. ; Thimell, M. ; El Allaf, D. ; Vítovec, J. ; Aldershvile, J. ; Halinen, M. ; Dietz, R. ; Neuhaus, K. L. ; Jánosi, A. ; Thorgeirsson, G. ; Dunselman, P. ; Gullestad, L. ; Kuch, J. ; Herlitz, J. ; Rickenbacher, P. ; Ball, S. ; Gottlieb, S. ; Deedwania, P. ; Vandenhoven, G. ; Nováková, I. ; Danker, S. ; Lundström, M. ; Meyer-Sabellek, W. ; Balla, I. ; Sveinsdottir, M. ; Dorhout, B. ; Hildebrandt, A. ; Szczurko, I. ; Larsson, C. ; Bucher, E. ; Scott, E. ; Dwyer, D. ; Julian, D. G. ; DeMets, D. L. ; Chatterjee, K. ; Feyzi, J. ; Lehto, S. ; Kárpáti, P. ; Motz, W. ; Samuelsson, O. ; Viersma, J. W. ; Andersson, B. ; Berthe, C. ; Boutefeu, J. M. ; Boxho, G. ; Decroly, P. ; Derbaudrenghien, J. P. ; Pirlet, J. ; Henry, P. ; Heyndrickx, G. ; Missault, L. ; Nannan, M. ; Timmermans, P. ; Vachiery, J. L. ; Van Mieghem, W. ; Vandenbossche, J. L. ; Dvorák, K. ; Herold, M. ; Hradec, J. ; Kána, A. ; Petr, P. ; Rybka, J. ; Smíd, J. ; Svítil, P. ; Toman, J. ; Agner, E. ; Amtorp, O. ; Egstrup, K. ; Eliasen, P. ; Gotzsche, C. O. ; Hildebrandt, P. ; Johannesen, A. ; Kaiser-Nielsen, P. ; Nielsen, H. ; Nielsen, P. E. ; Pedersen, F. ; Rokkedal Nielsen, J. ; Skagen, K. ; Honkanen, T. ; Hussi, E. ; Juvonen, J. ; Jääskeläinen, H. ; Rinne, J. ; Salonen, T. ; Andresen, D. ; Berwing, H. ; Bethge, [No Value] ; Beythien, [No Value] ; Bischoff, [No Value] ; Bundschu, [No Value] ; Daniel, [No Value] ; Darius, [No Value] ; Delius, [No Value] ; Drude, [No Value] ; Dingerkus, [No Value] ; Dück, [No Value] ; Eichler, [No Value] ; Fach, [No Value] ; Förster, A. ; Girth, [No Value] ; Goss, [No Value] ; Hahn, [No Value] ; Hambrecht, [No Value] ; Hauf, G. F. ; Heinemann, [No Value] ; Hepp, [No Value] ; Janka, [No Value] ; Klocke, [No Value] ; Konz, [No Value] ; Krosse, B. ; Kühlkamp, [No Value] ; Lewek, [No Value] ; Lüderitz, B. ; Löbe, [No Value] ; Maier, [No Value] ; Melchior, [No Value] ; Müller, [No Value] ; Mäurer, [No Value] ; Nast, [No Value] ; Neuhaus, [No Value] ; Obst, [No Value] ; Odemar, [No Value] ; von Olshausen, K. E. ; Pomykaj, [No Value] ; Schmailzl, K. J G ; Schrader, [No Value] ; Schröder, [No Value] ; Schwimmbeck, P. L. ; Sigmund, M. ; Simon, [No Value] ; Strasser, [No Value] ; Thilo, [No Value] ; Vöhringer, [No Value] ; Völler, H. ; Weibrodt, [No Value] ; Wirtz, [No Value] ; Wunderlich, [No Value] ; Czuriga, I. ; Hetey, M. ; Katona, A. ; Lengyel, M. ; Nyárádi, A. ; Rednik, A. ; Sándori, K. ; Szabó, P. ; Tarján, J. ; Tenczer, J. ; Timár, S. ; Vályi, P. ; Veress, G. ; Zámolyi, K. ; Öze, B. ; Thorgeirsson, Ge ; Thorgeirsson, Gu ; Bernink, P. J L M ; Bredero, A. C. ; Breedveld, R. W. ; Breuls, P. N W M ; Bucx, J. J J ; Cornel, J. H. ; De Milliano, P. A R ; Dunselman, P. H J M ; Hamer, B. J B ; Holwerda, N. L. ; Hoogsteen, J. ; Hoorntje, J. C A ; Kragten, J. A. ; Liem, A. H. ; Linssen, G. C M ; Michels, H. R. ; Ramdat Misier, A. R. ; Schaafsma, H. J. ; Sijbring, P. ; Taverne, R. J T ; Van Kempen, L. H J ; Van Stralen, R. ; Van Veldhuisen, P. J. ; Veerhoek, M. J. ; Werter, C. J P J ; Wesdorp, J. C L ; Willems, A. R. ; Withagen, A. J A M ; Zwart, P. A G ; Bjornerheim, R. ; Dahle, M. ; Dickstein, K. ; Froland, G. S. ; Gundersen, T. ; Hofsoy, K. ; Hole, T. L. ; Johansen, T. ; Mannsverk, J. ; Nesje, P. ; Omland, T. M. ; Sjödin, C. ; Smith, P. ; Tjonndal, H. A. ; Vikesdal, O. ; Waage, K. ; Adamus, [No Value] ; Jaworska, K. ; Kolodziej, P. ; Kornacewicz-Jach, Z. ; Krzemiñska-Pakula, M. ; Piotrowski, J. W. ; Piwowarska, W. ; Stogowski, A. ; Wodniecki, J. ; Wrabec, K. ; Ahlström, P. ; Ekdahl, S. ; Hemmingson, L. O. ; Holmberg, L. ; Lernfelt, B. ; Nilsson B Widgren, H. ; Ångman, K. ; Erne, P. ; Mohacsi, P. ; Polikar, R. ; Schläpfer, H. ; Batin, P. ; Berkin, K. E. ; Callaghan, T. S. ; Forfar, J. ; Frenneaux, M. ; Greenbaum, R. A. ; Maltz, M. ; Murdoch, D. ; Reynolds, G. ; Stephens, J. ; Struthers, A. ; Swan, J. ; Tildesley, G. ; Abbasi, A. ; Alagona, P. ; Alderman, J. ; Alipour, M. ; Anderson, J. L. ; Ansari, Z. ; Ashraf, M. ; Beanblossom, B. T. ; Bennett, S. ; Benvenuti, D. ; Berk, M. R. ; Bhalla, R. ; Bilazarian, S. D. ; Browne, K. F. ; MBuchter, C. ; Carlson, R. ; Carlson, C. J. ; Danisa, K. ; Dauber, I. ; DeWood, M. A. ; Dennish, G. ; Denny, D. M. ; DiBianco, R. ; Diller, P. M. ; Dunlap, M. ; Dowd, K. ; Edmiston, A. ; El Shahawy, M. ; Elkayam, U. ; Farnham, J. ; Fenster, P. ; Friedman, S. ; Heywood, T. ; Galichia, J. P. ; Geller, M. ; Ghali, J. K. ; Gheorghiade, M. ; Giles, T. ; Gillespe, R. ; Goldberg, G. ; Goldberg, M. C. ; Goldscher, D. A. ; Gooden, G. P. ; Goodman, M. ; Goodman, L. ; Gorwit, J. ; Gottlieb, S. S. ; Gradman, A. ; Grech, D. ; Hack, T. ; Hall, J. H. ; Hattenhauer, M. T. ; Higginbotham, M. B. ; Hutchins, S. ; Imburgia, M. ; Iteld, B. J. ; Jackson, B. ; Jafri, S. ; Jauch, W. ; Jennison, S. ; Kahn, B. H. ; Kao, W. ; Kaplan, K. ; Karlsberg, R. ; Kennedy, H. L. ; Kennedy, J. J. ; Kirkegaard, L. ; Kraus, D. H. ; LaBresh, K. ; Lalonde, L. ; Lesser, M. F. ; Levites, R. ; Levy, M. ; Lewis, R. K. ; Loh, I. K. ; Madyoon, H. ; Maislos, F. ; Mann, D. ; Maurice, G. L. ; Nisar, A. ; Old, W. ; Pappas, J. D. ; Phadke, K. ; Promisloff, S. ; Rashkow, A. M. ; Reeves, B. ; Rosen, J. H. ; Rotman, M. ; Saleem, T. ; Savran, S. V. ; Shah, R. ; Shalev, Y. ; Shanes, J. G. ; O'Shaughnessy, M. ; Silverman, B. ; Steingart, R. M. ; Swenson, L. ; Syed, K. ; Thadani, U. ; Thorsen, R. D. ; Tonkon, M. J. ; Touchon, R. ; Uhl, G. ; Vaska, K. J. ; Wagner, S. G. ; Weaver, C. J. ; Weiss, R. J. ; Wickemeyer, W. J. ; Willens, H. J. ; Wilson, J. R. ; Wright, R. ; Yellen, L. / Effect of metoprolol CR/XL in chronic heart failure : Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). In: Lancet. 1999 ; Vol. 353, No. 9169. pp. 2001-2007.
@article{07574c767b6a4d2f9da276ec88ae7213,
title = "Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)",
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.",
author = "A. Hjalmarson and S. Goldstein and B. Fagerberg and H. Wedel and F. Waagstein and J. Kjekshus and J. Wikstrand and G. Westergren and M. Thimell and {El Allaf}, D. and J. V{\'i}tovec and J. Aldershvile and M. Halinen and R. Dietz and Neuhaus, {K. L.} and A. J{\'a}nosi and G. Thorgeirsson and P. Dunselman and L. Gullestad and J. Kuch and J. Herlitz and P. Rickenbacher and S. Ball and S. Gottlieb and P. Deedwania and G. Vandenhoven and I. Nov{\'a}kov{\'a} and S. Danker and M. Lundstr{\"o}m and W. Meyer-Sabellek and I. Balla and M. Sveinsdottir and B. Dorhout and A. Hildebrandt and I. Szczurko and C. Larsson and E. Bucher and E. Scott and D. Dwyer and Julian, {D. G.} and DeMets, {D. L.} and K. Chatterjee and J. Feyzi and S. Lehto and P. K{\'a}rp{\'a}ti and W. Motz and O. Samuelsson and Viersma, {J. W.} and B. Andersson and C. Berthe and Boutefeu, {J. M.} and G. Boxho and P. Decroly and Derbaudrenghien, {J. P.} and J. Pirlet and P. Henry and G. Heyndrickx and L. Missault and M. Nannan and P. Timmermans and Vachiery, {J. L.} and {Van Mieghem}, W. and Vandenbossche, {J. L.} and K. Dvor{\'a}k and M. Herold and J. Hradec and A. K{\'a}na and P. Petr and J. Rybka and J. Sm{\'i}d and P. Sv{\'i}til and J. Toman and E. Agner and O. Amtorp and K. Egstrup and P. Eliasen and Gotzsche, {C. O.} and P. Hildebrandt and A. Johannesen and P. Kaiser-Nielsen and H. Nielsen and Nielsen, {P. E.} and F. Pedersen and {Rokkedal Nielsen}, J. and K. Skagen and T. Honkanen and E. Hussi and J. Juvonen and H. J{\"a}{\"a}skel{\"a}inen and J. Rinne and T. Salonen and D. Andresen and H. Berwing and Bethge, {[No Value]} and Beythien, {[No Value]} and Bischoff, {[No Value]} and Bundschu, {[No Value]} and Daniel, {[No Value]} and Darius, {[No Value]} and Delius, {[No Value]} and Drude, {[No Value]} and Dingerkus, {[No Value]} and D{\"u}ck, {[No Value]} and Eichler, {[No Value]} and Fach, {[No Value]} and A. F{\"o}rster and Girth, {[No Value]} and Goss, {[No Value]} and Hahn, {[No Value]} and Hambrecht, {[No Value]} and Hauf, {G. F.} and Heinemann, {[No Value]} and Hepp, {[No Value]} and Janka, {[No Value]} and Klocke, {[No Value]} and Konz, {[No Value]} and B. Krosse and K{\"u}hlkamp, {[No Value]} and Lewek, {[No Value]} and B. L{\"u}deritz and L{\"o}be, {[No Value]} and Maier, {[No Value]} and Melchior, {[No Value]} and M{\"u}ller, {[No Value]} and M{\"a}urer, {[No Value]} and Nast, {[No Value]} and Neuhaus, {[No Value]} and Obst, {[No Value]} and Odemar, {[No Value]} and {von Olshausen}, {K. E.} and Pomykaj, {[No Value]} and Schmailzl, {K. J G} and Schrader, {[No Value]} and Schr{\"o}der, {[No Value]} and Schwimmbeck, {P. L.} and M. Sigmund and Simon, {[No Value]} and Strasser, {[No Value]} and Thilo, {[No Value]} and V{\"o}hringer, {[No Value]} and H. V{\"o}ller and Weibrodt, {[No Value]} and Wirtz, {[No Value]} and Wunderlich, {[No Value]} and I. Czuriga and M. Hetey and A. Katona and M. Lengyel and A. Ny{\'a}r{\'a}di and A. Rednik and K. S{\'a}ndori and P. Szab{\'o} and J. Tarj{\'a}n and J. Tenczer and S. Tim{\'a}r and P. V{\'a}lyi and G. Veress and K. Z{\'a}molyi and B. {\"O}ze and Ge Thorgeirsson and Gu Thorgeirsson 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 J. Hoogsteen and Hoorntje, {J. C A} and Kragten, {J. A.} and Liem, {A. H.} and Linssen, {G. C M} and Michels, {H. R.} and {Ramdat Misier}, {A. R.} and Schaafsma, {H. J.} and P. Sijbring 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 R. Bjornerheim and M. Dahle and K. Dickstein and Froland, {G. S.} and T. Gundersen and K. Hofsoy and Hole, {T. L.} and T. Johansen and J. Mannsverk and P. Nesje and Omland, {T. M.} and C. Sj{\"o}din and P. Smith and Tjonndal, {H. A.} and O. Vikesdal and K. Waage and Adamus, {[No Value]} and K. Jaworska and P. Kolodziej and Z. Kornacewicz-Jach and M. Krzemi{\~n}ska-Pakula and Piotrowski, {J. W.} and W. Piwowarska and A. Stogowski and J. Wodniecki and K. Wrabec and P. Ahlstr{\"o}m and S. Ekdahl and Hemmingson, {L. O.} and L. Holmberg and B. Lernfelt and {Nilsson B Widgren}, H. and K. {\AA}ngman and P. Erne and P. Mohacsi and R. Polikar and H. Schl{\"a}pfer and P. Batin and Berkin, {K. E.} and Callaghan, {T. S.} and J. Forfar and M. Frenneaux and Greenbaum, {R. A.} and M. Maltz and D. Murdoch and G. Reynolds and J. Stephens and A. Struthers and J. Swan and G. Tildesley and A. Abbasi and P. Alagona and J. Alderman and M. Alipour and Anderson, {J. L.} and Z. Ansari and M. Ashraf and Beanblossom, {B. T.} and S. Bennett and D. Benvenuti and Berk, {M. R.} and R. Bhalla and Bilazarian, {S. D.} and Browne, {K. F.} and C. MBuchter and R. Carlson and Carlson, {C. J.} and K. Danisa and I. Dauber and DeWood, {M. A.} and G. Dennish and Denny, {D. M.} and R. DiBianco and Diller, {P. M.} and M. Dunlap and K. Dowd and A. Edmiston and {El Shahawy}, M. and U. Elkayam and J. Farnham and P. Fenster and S. Friedman and T. Heywood and Galichia, {J. P.} and M. Geller and Ghali, {J. K.} and M. Gheorghiade and T. Giles and R. Gillespe and G. Goldberg and Goldberg, {M. C.} and Goldscher, {D. A.} and Gooden, {G. P.} and M. Goodman and L. Goodman and J. Gorwit and Gottlieb, {S. S.} and A. Gradman and D. Grech and T. Hack and Hall, {J. H.} and Hattenhauer, {M. T.} and Higginbotham, {M. B.} and S. Hutchins and M. Imburgia and Iteld, {B. J.} and B. Jackson and S. Jafri and W. Jauch and S. Jennison and Kahn, {B. H.} and W. Kao and K. Kaplan and R. Karlsberg and Kennedy, {H. L.} and Kennedy, {J. J.} and L. Kirkegaard and Kraus, {D. H.} and K. LaBresh and L. Lalonde and Lesser, {M. F.} and R. Levites and M. Levy and Lewis, {R. K.} and Loh, {I. K.} and H. Madyoon and F. Maislos and D. Mann and Maurice, {G. L.} and A. Nisar and W. Old and Pappas, {J. D.} and K. Phadke and S. Promisloff and Rashkow, {A. M.} and B. Reeves and Rosen, {J. H.} and M. Rotman and T. Saleem and Savran, {S. V.} and R. Shah and Y. Shalev and Shanes, {J. G.} and M. O'Shaughnessy and B. Silverman and Steingart, {R. M.} and L. Swenson and K. Syed and U. Thadani and Thorsen, {R. D.} and Tonkon, {M. J.} and R. Touchon and G. Uhl and Vaska, {K. J.} and Wagner, {S. G.} and Weaver, {C. J.} and Weiss, {R. J.} and Wickemeyer, {W. J.} and Willens, {H. J.} and Wilson, {J. R.} and R. Wright and L. Yellen",
year = "1999",
month = "6",
day = "12",
doi = "10.1016/S0140-6736(99)04440-2",
language = "English",
volume = "353",
pages = "2001--2007",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "9169",

}

TY - JOUR

T1 - Effect of metoprolol CR/XL in chronic heart failure

T2 - Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)

AU - Hjalmarson, A.

AU - Goldstein, S.

AU - Fagerberg, B.

AU - Wedel, H.

AU - Waagstein, F.

AU - Kjekshus, J.

AU - Wikstrand, J.

AU - Westergren, G.

AU - Thimell, M.

AU - El Allaf, D.

AU - Vítovec, J.

AU - Aldershvile, J.

AU - Halinen, M.

AU - Dietz, R.

AU - Neuhaus, K. L.

AU - Jánosi, A.

AU - Thorgeirsson, G.

AU - Dunselman, P.

AU - Gullestad, L.

AU - Kuch, J.

AU - Herlitz, J.

AU - Rickenbacher, P.

AU - Ball, S.

AU - Gottlieb, S.

AU - Deedwania, P.

AU - Vandenhoven, G.

AU - Nováková, I.

AU - Danker, S.

AU - Lundström, M.

AU - Meyer-Sabellek, W.

AU - Balla, I.

AU - Sveinsdottir, M.

AU - Dorhout, B.

AU - Hildebrandt, A.

AU - Szczurko, I.

AU - Larsson, C.

AU - Bucher, E.

AU - Scott, E.

AU - Dwyer, D.

AU - Julian, D. G.

AU - DeMets, D. L.

AU - Chatterjee, K.

AU - Feyzi, J.

AU - Lehto, S.

AU - Kárpáti, P.

AU - Motz, W.

AU - Samuelsson, O.

AU - Viersma, J. W.

AU - Andersson, B.

AU - Berthe, C.

AU - Boutefeu, J. M.

AU - Boxho, G.

AU - Decroly, P.

AU - Derbaudrenghien, J. P.

AU - Pirlet, J.

AU - Henry, P.

AU - Heyndrickx, G.

AU - Missault, L.

AU - Nannan, M.

AU - Timmermans, P.

AU - Vachiery, J. L.

AU - Van Mieghem, W.

AU - Vandenbossche, J. L.

AU - Dvorák, K.

AU - Herold, M.

AU - Hradec, J.

AU - Kána, A.

AU - Petr, P.

AU - Rybka, J.

AU - Smíd, J.

AU - Svítil, P.

AU - Toman, J.

AU - Agner, E.

AU - Amtorp, O.

AU - Egstrup, K.

AU - Eliasen, P.

AU - Gotzsche, C. O.

AU - Hildebrandt, P.

AU - Johannesen, A.

AU - Kaiser-Nielsen, P.

AU - Nielsen, H.

AU - Nielsen, P. E.

AU - Pedersen, F.

AU - Rokkedal Nielsen, J.

AU - Skagen, K.

AU - Honkanen, T.

AU - Hussi, E.

AU - Juvonen, J.

AU - Jääskeläinen, H.

AU - Rinne, J.

AU - Salonen, T.

AU - Andresen, D.

AU - Berwing, H.

AU - Bethge, [No Value]

AU - Beythien, [No Value]

AU - Bischoff, [No Value]

AU - Bundschu, [No Value]

AU - Daniel, [No Value]

AU - Darius, [No Value]

AU - Delius, [No Value]

AU - Drude, [No Value]

AU - Dingerkus, [No Value]

AU - Dück, [No Value]

AU - Eichler, [No Value]

AU - Fach, [No Value]

AU - Förster, A.

AU - Girth, [No Value]

AU - Goss, [No Value]

AU - Hahn, [No Value]

AU - Hambrecht, [No Value]

AU - Hauf, G. F.

AU - Heinemann, [No Value]

AU - Hepp, [No Value]

AU - Janka, [No Value]

AU - Klocke, [No Value]

AU - Konz, [No Value]

AU - Krosse, B.

AU - Kühlkamp, [No Value]

AU - Lewek, [No Value]

AU - Lüderitz, B.

AU - Löbe, [No Value]

AU - Maier, [No Value]

AU - Melchior, [No Value]

AU - Müller, [No Value]

AU - Mäurer, [No Value]

AU - Nast, [No Value]

AU - Neuhaus, [No Value]

AU - Obst, [No Value]

AU - Odemar, [No Value]

AU - von Olshausen, K. E.

AU - Pomykaj, [No Value]

AU - Schmailzl, K. J G

AU - Schrader, [No Value]

AU - Schröder, [No Value]

AU - Schwimmbeck, P. L.

AU - Sigmund, M.

AU - Simon, [No Value]

AU - Strasser, [No Value]

AU - Thilo, [No Value]

AU - Vöhringer, [No Value]

AU - Völler, H.

AU - Weibrodt, [No Value]

AU - Wirtz, [No Value]

AU - Wunderlich, [No Value]

AU - Czuriga, I.

AU - Hetey, M.

AU - Katona, A.

AU - Lengyel, M.

AU - Nyárádi, A.

AU - Rednik, A.

AU - Sándori, K.

AU - Szabó, P.

AU - Tarján, J.

AU - Tenczer, J.

AU - Timár, S.

AU - Vályi, P.

AU - Veress, G.

AU - Zámolyi, K.

AU - Öze, B.

AU - Thorgeirsson, Ge

AU - Thorgeirsson, Gu

AU - Bernink, P. J L M

AU - Bredero, A. C.

AU - Breedveld, R. W.

AU - Breuls, P. N W M

AU - Bucx, J. J J

AU - Cornel, J. H.

AU - De Milliano, P. A R

AU - Dunselman, P. H J M

AU - Hamer, B. J B

AU - Holwerda, N. L.

AU - Hoogsteen, J.

AU - Hoorntje, J. C A

AU - Kragten, J. A.

AU - Liem, A. H.

AU - Linssen, G. C M

AU - Michels, H. R.

AU - Ramdat Misier, A. R.

AU - Schaafsma, H. J.

AU - Sijbring, P.

AU - Taverne, R. J T

AU - Van Kempen, L. H J

AU - Van Stralen, R.

AU - Van Veldhuisen, P. J.

AU - Veerhoek, M. J.

AU - Werter, C. J P J

AU - Wesdorp, J. C L

AU - Willems, A. R.

AU - Withagen, A. J A M

AU - Zwart, P. A G

AU - Bjornerheim, R.

AU - Dahle, M.

AU - Dickstein, K.

AU - Froland, G. S.

AU - Gundersen, T.

AU - Hofsoy, K.

AU - Hole, T. L.

AU - Johansen, T.

AU - Mannsverk, J.

AU - Nesje, P.

AU - Omland, T. M.

AU - Sjödin, C.

AU - Smith, P.

AU - Tjonndal, H. A.

AU - Vikesdal, O.

AU - Waage, K.

AU - Adamus, [No Value]

AU - Jaworska, K.

AU - Kolodziej, P.

AU - Kornacewicz-Jach, Z.

AU - Krzemiñska-Pakula, M.

AU - Piotrowski, J. W.

AU - Piwowarska, W.

AU - Stogowski, A.

AU - Wodniecki, J.

AU - Wrabec, K.

AU - Ahlström, P.

AU - Ekdahl, S.

AU - Hemmingson, L. O.

AU - Holmberg, L.

AU - Lernfelt, B.

AU - Nilsson B Widgren, H.

AU - Ångman, K.

AU - Erne, P.

AU - Mohacsi, P.

AU - Polikar, R.

AU - Schläpfer, H.

AU - Batin, P.

AU - Berkin, K. E.

AU - Callaghan, T. S.

AU - Forfar, J.

AU - Frenneaux, M.

AU - Greenbaum, R. A.

AU - Maltz, M.

AU - Murdoch, D.

AU - Reynolds, G.

AU - Stephens, J.

AU - Struthers, A.

AU - Swan, J.

AU - Tildesley, G.

AU - Abbasi, A.

AU - Alagona, P.

AU - Alderman, J.

AU - Alipour, M.

AU - Anderson, J. L.

AU - Ansari, Z.

AU - Ashraf, M.

AU - Beanblossom, B. T.

AU - Bennett, S.

AU - Benvenuti, D.

AU - Berk, M. R.

AU - Bhalla, R.

AU - Bilazarian, S. D.

AU - Browne, K. F.

AU - MBuchter, C.

AU - Carlson, R.

AU - Carlson, C. J.

AU - Danisa, K.

AU - Dauber, I.

AU - DeWood, M. A.

AU - Dennish, G.

AU - Denny, D. M.

AU - DiBianco, R.

AU - Diller, P. M.

AU - Dunlap, M.

AU - Dowd, K.

AU - Edmiston, A.

AU - El Shahawy, M.

AU - Elkayam, U.

AU - Farnham, J.

AU - Fenster, P.

AU - Friedman, S.

AU - Heywood, T.

AU - Galichia, J. P.

AU - Geller, M.

AU - Ghali, J. K.

AU - Gheorghiade, M.

AU - Giles, T.

AU - Gillespe, R.

AU - Goldberg, G.

AU - Goldberg, M. C.

AU - Goldscher, D. A.

AU - Gooden, G. P.

AU - Goodman, M.

AU - Goodman, L.

AU - Gorwit, J.

AU - Gottlieb, S. S.

AU - Gradman, A.

AU - Grech, D.

AU - Hack, T.

AU - Hall, J. H.

AU - Hattenhauer, M. T.

AU - Higginbotham, M. B.

AU - Hutchins, S.

AU - Imburgia, M.

AU - Iteld, B. J.

AU - Jackson, B.

AU - Jafri, S.

AU - Jauch, W.

AU - Jennison, S.

AU - Kahn, B. H.

AU - Kao, W.

AU - Kaplan, K.

AU - Karlsberg, R.

AU - Kennedy, H. L.

AU - Kennedy, J. J.

AU - Kirkegaard, L.

AU - Kraus, D. H.

AU - LaBresh, K.

AU - Lalonde, L.

AU - Lesser, M. F.

AU - Levites, R.

AU - Levy, M.

AU - Lewis, R. K.

AU - Loh, I. K.

AU - Madyoon, H.

AU - Maislos, F.

AU - Mann, D.

AU - Maurice, G. L.

AU - Nisar, A.

AU - Old, W.

AU - Pappas, J. D.

AU - Phadke, K.

AU - Promisloff, S.

AU - Rashkow, A. M.

AU - Reeves, B.

AU - Rosen, J. H.

AU - Rotman, M.

AU - Saleem, T.

AU - Savran, S. V.

AU - Shah, R.

AU - Shalev, Y.

AU - Shanes, J. G.

AU - O'Shaughnessy, M.

AU - Silverman, B.

AU - Steingart, R. M.

AU - Swenson, L.

AU - Syed, K.

AU - Thadani, U.

AU - Thorsen, R. D.

AU - Tonkon, M. J.

AU - Touchon, R.

AU - Uhl, G.

AU - Vaska, K. J.

AU - Wagner, S. G.

AU - Weaver, C. J.

AU - Weiss, R. J.

AU - Wickemeyer, W. J.

AU - Willens, H. J.

AU - Wilson, J. R.

AU - Wright, R.

AU - Yellen, L.

PY - 1999/6/12

Y1 - 1999/6/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033549290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033549290&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(99)04440-2

DO - 10.1016/S0140-6736(99)04440-2

M3 - Article

C2 - 10376614

AN - SCOPUS:0033549290

VL - 353

SP - 2001

EP - 2007

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9169

ER -