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 language | English (US) |
|---|---|
| Pages (from-to) | 2001-2007 |
| Number of pages | 7 |
| Journal | Lancet |
| Volume | 353 |
| Issue number | 9169 |
| DOIs | |
| State | Published - Jun 12 1999 |
ASJC Scopus subject areas
- General Medicine
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In: Lancet, Vol. 353, No. 9169, 12.06.1999, p. 2001-2007.
Research output: Contribution to journal › Article › peer-review
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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.
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AU - Maislos, F.
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AU - Phadke, K.
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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.
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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
SN - 0140-6736
VL - 353
SP - 2001
EP - 2007
JO - Lancet
JF - Lancet
IS - 9169
ER -