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Medical Forum / General / Cardiology / August 2007Effect of carvedilol and metoprolol on the mode of death in patients
Eur J Heart Fail. 2007 Aug 21; [Epub ahead of print] Effect of carvedilol and metoprolol on the mode of death in patients with heart failure. Remme WJ, Cleland JG, Erhardt L, Spark P, Torp-Pedersen C, Metra M, Komajda M, Moullet C, Lukas MA, Poole-Wilson P, Di Lenarda A, Swedberg K. Sticares Cardiovascular Research Foundation, P.O. Box 882, 3160 AB Rhoon, The Netherlands. 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. PMID: 17716943 [PubMed - as supplied by publisher]  SignatureS Jersey USA Zone 5 Shade This article is posted under fair use rules in accordance with Title 17 U.S.C. Section 107, and is strictly for the educational and informative purposes. This material is distributed without profit. http://www.ocutech.com/ High tech Vison aid Interesting. Thanks, Bill. -- Jim Chinnis Warrenton, Virginia, USA > Interesting. Thanks, Bill. > -- > Jim Chinnis Warrenton, Virginia, USA Well if you never mentioned carvedilol in an earlier post I never would have found it. Thank You Jim! Bill SignatureS Jersey USA Zone 5 Shade This article is posted under fair use rules in accordance with Title 17 U.S.C. Section 107, and is strictly for the educational and informative purposes. This material is distributed without profit. http://www.ocutech.com/ High tech Vison aid > Eur J Heart Fail. 2007 Aug 21; [Epub ahead of print] > [quoted text clipped - 32 lines] > vascular events. > PMID: 17716943 [PubMed - as supplied by publisher] The COMET trial used an inappropriately low dose of metoprolol, making its results less useful. SignatureDavid Rind drind@caregroup.harvard.edu > > Eur J Heart Fail. 2007 Aug 21; [Epub ahead of print] > > [quoted text clipped - 35 lines] > The COMET trial used an inappropriately low dose of metoprolol, making > its results less useful. Where do you find info like that ? I used to have a scifinder chair CAS and it had useful front end tools but it still used Pubmed and other private databases. Bill SignatureS Jersey USA Zone 5 Shade This article is posted under fair use rules in accordance with Title 17 U.S.C. Section 107, and is strictly for the educational and informative purposes. This material is distributed without profit. http://www.ocutech.com/ High tech Vison aid > > Eur J Heart Fail. 2007 Aug 21; [Epub ahead of print] > > [quoted text clipped - 35 lines] > The COMET trial used an inappropriately low dose of metoprolol, making > its results less useful. The target dose was 100 mg of metoprolol tartrate versus 50 mg of carvedilol. It was certainly enough metoprolol to increase the incidence of diabetic events. Source: http://heart.bmj.com/cgi/content/abstract/93/8/968 Thus, it remains a matter of debate whether 100 mg of metoprolol tartrate was an inappropriately low dose. Be hungry... be healthy... be hungrier... be blessed: http://TheWellnessFoundation.com/PressRelease Prayerfully in Jesus' awesome love, Andrew <>< -- Andrew B. Chung, MD/PhD Cardiologist > Thus, it remains a matter of debate whether 100 mg of metoprolol > tartrate was an inappropriately low dose. I agree that it is a matter of debate (in that there are clearly experts who would take either side of the point I was making). However: 1) The dose used was lower than the dose that had been used in the earlier heart failure trials with metoprolol. 2) They used tartrate rather than the long-acting succinate that was used in the heart failure trials. 3) The achieved heart rate reduction was substantially greater with carvedilol, showing that the degree of beta blockade was not equivalent in the two arms. I do not find COMET convincing that carvedilol is superior to appropriate doses of long-acting metoprolol. SignatureDavid Rind drind@caregroup.harvard.edu > Andrew, in the Holy Spirit, boldly wrote: > [quoted text clipped - 6 lines] > 1) The dose used was lower than the dose that had been used in the > earlier heart failure trials with metoprolol. The justification would be that the formulation is different (tartrate instead of succinate). > 2) They used tartrate rather than the long-acting succinate that was > used in the heart failure trials. This would not go toward supporting your position about the dosage being too low. A case could be made that for a head-to-head comparison with short- acting carvedilol which is dosed twice daily that short-acting twice daily metoprolol tartrate was appropriately used. > 3) The achieved heart rate reduction was substantially greater with > carvedilol, showing that the degree of beta blockade was not equivalent > in the two arms. It is not clear that heart rate reduction in heart failure patients is a good measure of degree of beta blockade. The case could be made that because blood pressure lowering in both arms were comparable that so was the degree of beta blockade. > I do not find COMET convincing that carvedilol is superior to > appropriate doses of long-acting metoprolol. However, it does serve to justify preferential use of carvedilol over short-acting metoprolol tartrate in heart failure patients. We will have to wait for head-to-head comparisons of long-acting forms of carvedilol with long-acting metoprolol succinate to determine which is better. May GOD bless you in HIS mighty way making you healthier (hungrier) than ever: http://HeartMDPhD.com/HolySpirit/PressRelease Prayerfully in Jesus' awesome love, Andrew <>< -- Andrew B. Chung, MD/PhD Cardiologist |
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