| 1. |
- Remme, W. J., et al.
(författare)
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Carvedilol protects better against vascular events than metoprolol in heart failure: results from COMET
- 2007
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Ingår i: Journal of the American College of Cardiology. - 1558-3597. ; 49:9, s. 963-71
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We explored whether vascular protection by carvedilol could contribute to its superior effects in the treatment of heart failure (HF) compared with metoprolol tartrate in the COMET (Carvedilol Or Metoprolol European Trial) study. BACKGROUND: Full adrenergic blockade by carvedilol and additional (e.g., antioxidative) properties may lead to vascular protection relative to beta-1 blockade alone, and contribute to its efficacy in HF treatment. METHODS: Three thousand twenty-nine patients with HF due to ischemic (51%) or idiopathic cardiomyopathy (44%) were randomized double-blind to carvedilol (n = 1,511) or metoprolol (n = 1,518) and followed for 58 months. Vascular end points were cardiovascular death, stroke, stroke death, myocardial infarction (MI), and unstable angina. RESULTS: The effect of carvedilol on cardiovascular death improved consistently in subgroups with prespecified baseline variables. Myocardial infarctions were reported in 69 carvedilol and 94 metoprolol patients (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52 to 0.97, p = 0.03). Cardiovascular death or nonfatal MI combined were reduced by 19% in carvedilol (HR 0.81, 95% CI 0.72 to 0.92, p = 0.0009 vs. metoprolol). Unstable angina was reported as an adverse event in 56 carvedilol and in 77 metoprolol patients (HR 0.71, 95% CI 0.501 to 0.998, p = 0.049). A stroke occurred in 65 carvedilol and 80 metoprolol patients (HR 0.79, 95% CI 0.57 to 1.10). Stroke or MI combined occurred in 130 carvedilol and 168 metoprolol patients (HR 0.75, 95% CI 0.60 to 0.95, p = 0.015), and fatal MI or fatal stroke occurred in 34 carvedilol and in 72 metoprolol patients (HR 0.46, 95% CI 0.31 to 0.69, p = 0.0002). Death after a nonfatal MI or stroke occurred in 61 of 124 carvedilol and in 106 of 160 metoprolol patients (HR 0.66, 95% CI 0.48 to 0.90, p = 0.0086). CONCLUSIONS: Carvedilol improves vascular outcomes better than metoprolol. These results suggest a ubiquitous protective effect of carvedilol against major vascular events.
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| 2. |
- Remme, W. J., et al.
(författare)
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Effect of carvedilol and metoprolol on the mode of death in patients with heart failure
- 2007
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Ingår i: Eur J Heart Fail. - : Wiley. - 1388-9842 .- 1879-0844. ; 9:11, s. 1128-35
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the COMET study, carvedilol improved survival compared to metoprolol tartrate in 3029 patients with NYHA II-IV heart failure and EF <35%, followed for an average of 58 months. AIMS: To evaluate whether the effect on overall mortality was specific for a particular mode of death. This may help to identify the mechanism of the observed difference. METHODS: Of the 1112 total deaths, 972 were adjudicated as cardiovascular, including 480 sudden, 365 circulatory failure (CF) and 51 stroke deaths. For each mode of death, the effect of pre-specified baseline variables was assessed, including sex, age, NYHA class, aetiology, heart rate, systolic blood pressure, EF, atrial fibrillation, previous myocardial infarction or hypertension, renal function, concomitant medication, and study treatment allocation. RESULTS: In multivariate Cox regression analyses, compared to metoprolol, carvedilol reduced cardiovascular (RR 0.80, CI 0.7-0.91, p=0.0009), sudden (RR 0.77, CI 0.64-0.93, p=0.0073) and stroke deaths (RR 0.37, CI 0.19-0.71, p=0.0027) with a non-significant trend for CF death (RR 0.83, CI 0.66-1.04, p=0.07). Treatment benefit with carvedilol did not differ between modes of death, except for a greater reduction in stroke death with carvedilol (competing risk analysis, p=0.0071 vs CF death). There were no interactions between treatment allocation and baseline characteristics. CONCLUSION: Mortality reduction with carvedilol compared to metoprolol appears relatively non-specific and could be consistent with a superior effect of carvedilol on cardiac function, arrhythmias or, in view of the greater reduction in stroke deaths, on vascular events.
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| 3. |
- Torp-Pedersen, C., et al.
(författare)
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The safety of amiodarone in patients with heart failure
- 2007
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Ingår i: J Card Fail. - 1532-8414. ; 13:5, s. 340-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Uncertainty persists about the safety and efficacy of amiodarone for the management of heart failure. METHODS AND RESULTS: We randomized 3029 patients with chronic heart failure to receive carvedilol or metoprolol and followed patients for a median of 58 months. One hundred fifty-five of 1466 patients in New York Heart Association (NYHA) Class II and 209 of 1563 in Class III or IV received amiodarone at baseline. Persistence with amiodarone treatment was high and 66% received amiodarone after 4 years. During follow-up, 38.7% and 58.9% of patients receiving amiodarone in NYHA Classes II and III + IV died versus 26.2% and 43.3% not receiving amiodarone (P < .001). This difference was maintained in multivariable analysis (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.2-1.7, P < .001). The difference was explained by an increased risk of death due to circulatory failure (HR 2.4, CI 1.9-3.1, P < .001) in patients receiving amiodarone. Sudden death was not different (HR 1.07, CI 0.8-1.4, P = .7). The increased risk was similar across NYHA classes with HR of 1.60 (CI 1.2-2.1, P < .001) in NYHA Class II versus 1.58 (CI 1.3-1.9, P < .001) in Classes III + IV. CONCLUSIONS: Treatment with amiodarone was associated with an increased risk of death from circulatory failure independent of functional class.
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| 4. |
- Cleland, J. G., et al.
(författare)
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A comparison of the effects of carvedilol and metoprolol on well-being, morbidity, and mortality (the "patient journey") in patients with heart failure: a report from the Carvedilol Or Metoprolol European Trial (COMET)
- 2006
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 47:8, s. 1603-11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study was designed to investigate the loss of well-being, in terms of life-years, overall and in patients randomized to metoprolol versus carvedilol in the Carvedilol Or Metoprolol European Trial (COMET). BACKGROUND: The ultimate objectives of treating patients with heart failure are to relieve suffering and prolong life. Although the effect of treatment on mortality is usually described in trials, the effects on patient well-being throughout the trials' courses are rarely reported. METHODS: A total of 3,029 patients randomized in the COMET study were included in the analysis. "Patient journey" was calculated by adjusting days alive and out of hospital over four years using a five-point score completed by the patient every four months, adjusted according to the need for intensification of diuretic therapy. Scores ranged from 0% (dead or hospitalized) to 100% (feeling very well). RESULTS: Over 48 months, 17% of all days were lost through death, 1% through hospitalization, 23% through impaired well-being, and 2% through the need for intensified therapy. Compared with metoprolol, carvedilol was associated with fewer days lost to death, with no increase in days lost due to impaired well-being or days in hospital. The "patient journey" score improved from a mean of 54.8% (SD 26.0) to 57.4% (SD 26.3%) (p < 0.0068). CONCLUSIONS: Despite treatment with beta-blockers, heart failure remains associated with a marked reduction in well-being and survival. Loss of quality-adjusted life-years through death and poor well-being seemed of similar magnitude over four years, and both were much larger than the loss that could be attributed to hospitalization.
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| 5. |
- Di Lenarda, A., et al.
(författare)
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Exchange of beta-blockers in heart failure patients. Experiences from the poststudy phase of COMET (the Carvedilol or Metoprolol European Trial)
- 2005
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842. ; 7:4, s. 640-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Carvedilol or Metoprolol European Trial (COMET) reported a significant survival benefit for carvedilol, a beta1-, beta2- and alpha1-blocker, vs. metoprolol tartrate, a beta1-selective blocker, in patients with mild-to-severe chronic heart failure (CHF). Patients on treatment with metoprolol might benefit from switching to carvedilol. AIM: To investigate the safety and tolerability of switching beta-blockers in CHF. METHODS: At the end of COMET, the Steering Committee recommended that study medication was stopped without unblinding, and patients were commenced on open-label beta-blockade at a dose equivalent to half the dose of blinded therapy, with subsequent titration to target or maximum tolerated dose. Patients were followed for 30 days. RESULTS: 1321 out of 1440 patients were transitioned to open-label treatment (76.8% to carvedilol). Serious adverse and CHF-related events were respectively 9.4% and 4.7% in those switching from carvedilol to metoprolol and 3.1% and 1.5% in patients switching from metoprolol to carvedilol. Patients who switched from carvedilol to metoprolol showed the highest mortality or hospitalisation rate (12.3%) in comparison with those who switched from metoprolol to carvedilol (3.1%, p<0.001) or who stayed on the same drug (carvedilol: 2.5%, p<0.001; metoprolol: 4.2%, p=0.04). Reducing the initial dose of the second beta-blocker maximised the safety of this strategy. Event rate was higher in patients with more severe heart failure and in those withdrawing from beta-blockade. CONCLUSION: Our data show that switching beta-blockers is a practical, safe and well-tolerated strategy to optimise treatment of CHF. Patients who switched to carvedilol showed the lowest rate of adverse events. A closer clinical monitoring is recommended during transition in high-risk patients.
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| 6. |
- Gustafsson, I., et al.
(författare)
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[Metabolic control by means of insulin in patients with type 2 diabetes and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity--secondary publication]
- 2006
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Ingår i: Ugeskr Laeger. - : Almindelige danske Lægeforening. - 1603-6824 .- 0041-5782. ; 168:6, s. 581-4
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Tidskriftsartikel (refereegranskat)abstract
- Patients with diabetes have an unfavourable prognosis after an acute myocardial infarction. The DIGAMI 2 study investigated the effect of various metabolic treatment strategies in type 2 diabetic patients with acute myocardial infarction: acutely introduced, long-term insulin treatment did not improve survival when compared with conventional management at similar levels of glucose control. However, good glucose control seems important since the glucose level was found to be a strong predictor of long-term mortality in this patient category.
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| 7. |
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| 8. |
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| 9. |
- Metra, M., et al.
(författare)
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Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial
- 2005
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 26:21, s. 2259-68
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We studied the influence of heart rate (HR), systolic blood pressure (SBP), and beta-blocker dose on outcome in the 2599 out of 3029 patients in Carvedilol Or Metoprolol European Trial (COMET) who were alive and on study drug at 4 months after randomization (time of first visit on maintenance therapy). METHODS AND RESULTS: By multivariable analysis, baseline HR, baseline SBP, and their change after 4 months were not independently related to subsequent outcome. In a multivariable analysis including clinical variables, HR above and SBP below the median value achieved at 4 months predicted subsequent increased mortality [relative risk (RR) for HR>68 b.p.m. 1.333; 95% confidence intervals (CI) 1.152-1.542; P<0.0001 and RR for SBP>120 mmHg 0.78; 95% CI 0.671-0.907; P<0.0013]. Achieving target beta-blocker dose was associated with a better outcome (RR 0.779; 95% CI 0.662-0.916; P<0.0025). The superiority of carvedilol as compared to metoprolol tartrate was maintained in a multivariable model (RR 0.767; 95% CI 0.663-0.887; P=0.0004) and there was no interaction with HR, SBP, or beta-blocker dose. CONCLUSION: Beta-blocker dose, HR, and SBP achieved during beta-blocker therapy have independent prognostic value in heart failure. None of these factors influenced the beneficial effects of carvedilol when compared with metoprolol tartrate at the pre-defined target doses used in COMET.
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| 10. |
- Metra, M., et al.
(författare)
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Should beta-blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET
- 2007
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Ingår i: Eur J Heart Fail. - : Wiley. - 1388-9842. ; 9:9, s. 901-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is unclear whether beta-blocker therapy should be reduced or withdrawn in patients who develop acute decompensated heart failure (HF). We studied the relationship between changes in beta-blocker dose and outcome in patients surviving a HF hospitalisation in COMET. METHODS: Patients hospitalised for HF were subdivided on the basis of the beta-blocker dose administered at the visit following hospitalisation, compared to that administered before. RESULTS: In COMET, 752/3029 patients (25%, 361 carvedilol and 391 metoprolol) had a non-fatal HF hospitalisation while on study treatment. Of these, 61 patients (8%) had beta-blocker treatment withdrawn, 162 (22%) had a dose reduction and 529 (70%) were maintained on the same dose. One-and two-year cumulative mortality rates were 28.7% and 44.6% for patients withdrawn from study medication, 37.4% and 51.4% for those with a reduced dosage (n.s.) and 19.1% and 32.5% for those maintained on the same dose (HR,1.59; 95%CI, 1.28-1.98; p<0.001, compared to the others). The result remained significant in a multivariable model: (HR, 1.30; 95%CI, 1.02-1.66; p=0.0318). No interaction with the beneficial effects of carvedilol, compared to metoprolol, on outcome was observed (p=0.8436). CONCLUSIONS: HF hospitalisations are associated with a high subsequent mortality. The risk of death is higher in patients who discontinue beta-blocker therapy or have their dose reduced. The increase in mortality is only partially explained by the worse prognostic profile of these patients.
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| 11. |
- Olsson, Lars G., 1970, et al.
(författare)
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Prognostic importance of plasma NT-pro BNP in chronic heart failure in patients treated with a beta-blocker: results from the Carvedilol Or Metoprolol European Trial (COMET) trial
- 2007
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Ingår i: Eur J Heart Fail. - 1388-9842. ; 9:8, s. 795-801
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Plasma levels of N-terminal pro-brain natriuretic peptide (NT-pro BNP) are increased in patients with chronic heart failure (CHF). Beta-blockers (BB) may influence these levels but it is unclear whether changes in NT-pro BNP reflect concomitant changes in prognosis. OBJECTIVES: To assess the prognostic importance of NT-pro BNP at baseline and during follow-up, in patients in whom beta-blocker therapy is initiated. METHODS: In COMET, 3029 patients with CHF in NYHA class II-IV and EF<35% were randomised to carvedilol or metoprolol tartrate and were followed for an average of 58 months. Blood samples were collected for the measurement of NT-pro BNP at baseline (n=1559) and during follow-up (n=309). RESULTS: Baseline plasma concentrations of NT-pro BNP above the median (1242 pg/ml) were associated with higher all-cause mortality (RR 2.77; 95% CI 2.33-3.3, p<0.001). Patients who achieved NT-pro BNP levels<400 pg/ml during follow-up had a lower subsequent mortality (RR 0.32; 95% CI 0.15-0.69, p=0.004). CONCLUSIONS: The plasma concentration of NT-pro BNP is a powerful predictor of mortality in patients with CHF. Patients who achieve an NT-pro BNP of <400 pg/ml subsequent to treatment with a beta-blocker have a favourable prognosis.
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| 12. |
- Swedberg, Karl, 1944, et al.
(författare)
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Prognostic relevance of atrial fibrillation in patients with chronic heart failure on long-term treatment with beta-blockers: results from COMET
- 2005
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 26:13, s. 1303-8
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Atrial fibrillation is common in patients with chronic heart failure (CHF). We analysed the risk associated with atrial fibrillation in a large cohort of patients with chronic heart failure all treated with a beta-blocker. METHODS AND RESULTS: In COMET, 3029 patients with CHF were randomized to carvedilol or metoprolol tartrate and followed for a mean of 58 months. We analysed the prognostic relevance on other outcomes of atrial fibrillation on the baseline electrocardiogram compared with no atrial fibrillation and the impact of new onset atrial fibrillation during follow-up. A multivariate analysis was performed using a Cox regression model where 10 baseline covariates were entered together with study treatment allocation. Six hundred patients (19.8%) had atrial fibrillation at baseline. These patients were older (65 vs. 61 years), included more men (88 vs.78%), had more severe symptoms [higher New York Heart Association (NYHA) class] and a longer duration of heart failure (all P<0.0001). Atrial fibrillation was associated with significantly increased mortality [relative risk (RR) 1.29: 95% CI 1.12-1.48; P<0.0001], higher all-cause death or hospitalization (RR 1.25: CI 1.13-1.38), and cardiovascular death or hospitalization for worsening heart failure (RR 1.34: CI 1.20-1.52), both P<0.0001. By multivariable analysis, atrial fibrillation no longer independently predicted mortality. Beneficial effects on mortality by carvedilol remained significant (RR 0.836: CI 0.74-0.94; P=0.0042). New onset atrial fibrillation during follow-up (n=580) was associated with significant increased risk for subsequent death in a time-dependent analysis (RR 1.90: CI 1.54-2.35; P<0.0001) regardless of treatment allocation and changes in NYHA class. CONCLUSION: In CHF, atrial fibrillation significantly increases the risk for death and heart failure hospitalization, but is not an independent risk factor for mortality after adjusting for other predictors of prognosis. Treatment with carvedilol compared with metoprolol offers additional benefits among patients with atrial fibrillation. Onset of new atrial fibrillation in patients on long-term beta-blocker therapy is associated with significant increased subsequent risk of mortality and morbidity.
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| 13. |
- Torp-Pedersen, C., et al.
(författare)
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Effects of metoprolol and carvedilol on cause-specific mortality and morbidity in patients with chronic heart failure--COMET
- 2005
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Ingår i: American heart journal. - 1097-6744. ; 149:2, s. 370-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Beta-blockers with different receptor bindings reduce mortality in patients with chronic heart failure. We compared the effects of the beta1-blocker metoprolol tartrate and the beta1-, beta2-, and alpha1-blocker carvedilol. METHODS: In a randomized double-blind design, 3029 patients with chronic congestive heart failure requiring diuretic therapy and with left ventricular dysfunction were randomized to treatment with carvedilol (n = 1511) or metoprolol tartrate (n = 1518) and titrated to target doses of 25 mg of carvedilol twice daily or 50 mg of metoprolol tartrate twice daily. The main outcome measures were total mortality and the combination of mortality or hospitalization for any cause. Secondary end points were cardiovascular death, combinations of morbidity and mortality, New York Heart Association class, worsening of heart failure, hospitalizations, and discontinuation of study therapy. RESULTS: A total of 512 and 600 patients in the carvedilol group and metoprolol group, respectively, died (hazard ratio [HR] 0.83, 95% CI 0.74-0.93, P = .0017). Cardiovascular death was reduced by carvedilol (HR 0.80, 95% CI 0.70-0.90, P = .0004). There were fewer sudden deaths and deaths caused by circulatory failure or by stroke in the carvedilol group. There was no difference in all-cause hospitalizations or in worsening heart failure between treatment groups. The incidence of fatal or nonfatal acute myocardial infarction was significantly lower in the carvedilol group (HR 0.71, 95% CI 0.52-0.97, P = .03). Discontinuations of study therapy were similar in the 2 groups. CONCLUSION: Compared with metoprolol tartrate, carvedilol reduced cardiovascular mortality, sudden death, death caused by circulatory failure, death caused by stroke, as well as fatal and nonfatal myocardial infarctions.
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| 14. |
- Torp-Pedersen, C., et al.
(författare)
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Effects of metoprolol and carvedilol on preexisting and new on-set diabetes in patients with chronic heart failure {inverted exclamation}V data from the Carvedilol or metoprolol European Trial (COMET)
- 2007
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Ingår i: Heart. - 1468-201X. ; 93:8, s. 968-973
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Tidskriftsartikel (refereegranskat)abstract
- Objective Beta-blocker therapy may worsen glucose metabolism. We studied the development of new onset diabetes in a large cohort of heart failure patients treated with either metoprolol or carvedilol. Design Prospective and retrospective analysis of a controlled clinical trial. Setting Multinational multicenter study Patients 3029 patients with chronic heart failure. Interventions Randomly assigned treatment with carvedilol (n=1511, target dose 50 mg daily) or metoprolol tartrate (n=1518, target dose 100 mg daily). Results Diabetic events (diabetic coma, peripheral gangrene, diabetic foot, de-creased glucose tolerance or hyperglycemia) and new onset diabetes (clinical di-agnosis, repeated high random glucose level or glucose lowering medication) were assessed in 2298 patients without diabetes at baseline. Diabetic events oc-curred in 122/1151 (10.6%) patients in the carvedilol group and 149/1147 (13.0%) patients in the metoprolol group (hazard ratio (HR) 0.78; 95% confi-dence interval (CI) 0.61-0.99, p=0.039). New onset diabetes was diagnosed in 119/1151 (10.4%) versus 145/1147 (12.6%) cases in the carvedilol and metoprolol treatment groups (HR 0.78, CI 0.61-0.998, p=0.048). Patients with diabetes at baseline had an increased mortality, compared to non-diabetics (45.3% versus, 33.9%; HR 1.45, CI 1.28-1.65). Both diabetics and non-diabetics at baseline had a similar reduction in mortality with carvedilol compared to metoprolol (RR 0.85; CI 0.69-1.06 and RR 0.82; CI, 0.71-0.94, respectively). Conclusion This study demonstrates both a high prevalence and incidence of diabetes in patients with heart failure over a course of 5 years. New onset diabe-tes was more likely to occur during treatment with metoprolol than during treat-ment with carvedilol.
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