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- Hjamarson, A, et al.
(författare)
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Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure. The Metoprolol CR/XL randomized intervention trial in congestive heart failure
- 2000
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Ingår i: Journal of the American Medical Association. - : JAMA. - 0221-7678. ; 283:10, s. 1295-1302
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Tidskriftsartikel (refereegranskat)abstract
- Results from recent studies on the effects of beta1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of beta1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored. OBJECTIVE: To examine the effects of the beta1-blocker controlled-release/extended-release metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure. DESIGN: Randomized, double-blind controlled trial, preceded by a 2-week single-blind placebo run-in period, conducted from February 14, 1997, to October 31, 1998, with a mean follow-up of 1 year. SETTING: Three hundred thirteen sites in 14 countries. PARTICIPANTS: Patients (n = 3991) with chronic heart failure, New York Heart Association (NYHA) functional class II to IV, and ejection fraction of 0.40 or less who were stabilized with optimum standard therapy. INTERVENTIONS: Patients were randomized to metoprolol CR/XL, 25 mg once per day (NYHA class II), or 12.5 mg once per day (NYHA class III or IV), titrated for 6 to 8 weeks up to a target dosage of 200 mg once per day (n = 1990); or matching placebo (n = 2001). MAIN OUTCOME MEASURES: Total mortality or any hospitalization (time to first event), number of hospitalizations for worsening heart failure, and change in NYHA class, by intervention group; quality of life was assessed in a substudy of 741 patients. RESULTS: The incidence of all predefined end points was lower in the metoprolol CR/XL group than in the placebo group, including total mortality or all-cause hospitalizations (the prespecified second primary end point; 641 vs 767 events; risk reduction, 19%; 95% confidence interval [CI], 10%-27%; P<.001); total mortality or hospitalizations due to worsening heart failure (311 vs 439 events; risk reduction, 31%; 95% CI, 20%-40%; P<.001), number of hospitalizations due to worsening heart failure (317 vs 451; P<.001); and number of days in hospital due to worsening heart failure (3401 vs 5303 days; P<.001). NYHA functional class, assessed by physicians, and McMaster Overall Treatment Evaluation score, assessed by patients, both improved in the metoprolol CR/XL group compared with the placebo group (P = .003 and P = .009, respectively). CONCLUSIONS: In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being.
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| 2. |
- Deedwania, P. C., et al.
(författare)
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Efficacy, safety and tolerability of beta-adrenergic blockade with metoprolol CR/XL in elderly patients with heart failure
- 2004
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Ingår i: Eur Heart J. - : Oxford University Press (OUP). - 0195-668X. ; 25:15, s. 1300-9
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the efficacy and tolerability of beta-blockade in elderly patients with heart failure in the MERIT-HF study. METHODS AND RESULTS: Cox proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). Risk reduction was defined as (1-HR). In patients > or = 65 years total mortality was reduced by 37% (95% CI 17% to 52%; p=0.0008), sudden death by 43% (95% CI 17% to 61%; p=0.0032), and death from worsening heart failure by 61% (95% CI 32% to 77%; p=0.0005). Hospitalisations for worsening heart failure was reduced by 36% (p=0.0006). Elderly patients with severe heart failure (NYHA class III/IV with ejection fraction < 0.25; n=425, and patients above 75 years (n=490) showed similar risk reductions. Metoprolol CR/XL was safe and well tolerated both during initiating therapy and during long-term follow-up. CONCLUSIONS: Metoprolol CR/XL was easily instituted, safe and well tolerated in elderly patients with systolic heart failure. The data suggest that these are the patients in whom treatment will have the greatest impact as shown by number of lives saved and number of hospitalisations avoided. The time has come to overcome the barriers that physicians perceive to beta-blocker treatment, and to provide it to the large number of elderly patients with heart failure in need of this therapy.
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| 3. |
- Ghali, J. K., et al.
(författare)
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Consistency of the beneficial effect of metoprolol succinate extended release across a wide range dose of angiotensin-converting enzyme inhibitors and digitalis
- 2004
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Ingår i: J Card Fail. - 1071-9164. ; 10:6, s. 452-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The effects of beta-blockade with different extent of angiotensin-converting enzyme inhibitors (ACEI) and digitalization are unknown. To assess the effect of metoprolol succinate controlled release/extended release (CR/XL) combined with high versus low doses of ACEI and digitalis, we analyzed data from The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) in which patients with heart failure and left ventricular ejection fraction < or =40% were randomized to metoprolol CR/XL versus placebo. METHODS AND RESULTS: Outcome was analyzed separately for those on a low dose (< or =median) of the ACEI or digitalis versus high dose (> median). The mean dose of ACEI in the high-dose group (n = 1457) was 3 times higher than that in the low-dose group (n = 2094). Mortality was reduced to a similar extent in the high- and low-dose ACEI subgroups (RR = .69 versus .64, respectively). Corresponding figures for combined mortality/all hospitalization and for mortality/hospitalization for heart failure were .85 versus .83, and .70 versus .68, respectively. Likewise, reduction in total mortality with metoprolol CR/XL was similar in patients receiving no digitalis (n = 1447; RR = .56), low dose (n = 1122; RR = .71), or high dose (n = 1421; RR = .71). CONCLUSION: This analysis of MERIT-HF demonstrates consistent and similar improvement in outcome of patients receiving metoprolol CR/XL when combined with either a high or low dose of an ACEI or digitalis, or no digitalis at all. Thus regardless of ACEI and digitalis dose and whether patients are treated with digitalis or not, it is very important to add a beta-blocker to the existing heart failure therapy. beta-blockers should not be withheld until target doses of ACEI have been achieved.
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