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Effect of metoprolol CR/XL in chronic heart failure; Metoprolol CR/XL. Randomised Intervention Trial in Congestive Heart Failure
[external].
1999 (English)In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 353, no 9169, 2001-2007 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
The Lancet Publishing Group , 1999. Vol. 353, no 9169, 2001-2007 p.
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:hb:diva-7901DOI: 10.1016/S0140-6736(99)04440-2Local ID: 2320/8651OAI: oai:DiVA.org:hb-7901DiVA: diva2:888783
Available from: 2015-12-22 Created: 2015-12-22 Last updated: 2017-03-21Bibliographically approved

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