COMET (study)
In COMET is a clinical study or a randomized, controlled trial that the relatively new and therefore expensive beta blockers compared carvedilol with the long-known and affordable metoprolol. The abbreviation COMET means Carvedilol Or Metoprolol European Trial .
Result
Significant reduction ( relative risk reduction ) in mortality by 17% with carvedilol compared to metoprolol
publication
Lancet 2003; 362: 7-13 ( Original title: Comparison of Carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomized controlled trial ) by Philip A. Poole-Wilson u. a.
Study occasion
For a long time it was unclear whether the more expensive combined beta 1 , beta 2 and alpha blocker carvedilol had advantages over a simple blockade of beta 1 receptors.
Study design
3,029 patients with heart failure ( NYHA II-IV stage) were randomized and assigned to either the carvedilol or metoprolol group. Requirements were there
- a left ventricular dysfunction with an EF <35%
- stable conditions under standard therapy with ACE inhibitors and diuretics
In the carvedilol group, treatment was gradually started with 3.125 mg twice a day up to the target dose of 25 mg twice a day; in the metoprolol group, treatment began gradually with 2 × 5 mg up to the target dose of 2 × 50 mg. Both groups tried to reach these target doses, so that the other drugs were partially reduced in the course of the study.
Duration of study: 58 months on average.
Statistical data
Only the average values are given here without the average deviations , which, however, as required by a good study, were comparable in both groups.
| Carvedilol (1511 patients) | Metoprolol (1518 patients) | |
| Age | 61.6 years | 62.3 years |
| Men | 1200 (79%) | 1217 (80%) |
| white | 1494 (99%) | 1504 (99%) |
| BMI | 26.9 | 26.8 |
| Systolic blood pressure | 126 mm Hg | 126 mm Hg |
| Diastolic blood pressure | 77 mm Hg | 77 mm Hg |
| Pulse | 81 mm Hg | 81 mm Hg |
| NYHA Stadium: | ||
| II | 730 (48%) | 736 (49%) |
| III | 732 (48%) | 716 (47%) |
| IV | 49 (3%) | 66 (4%) |
| Duration of heart failure | 42.6 months | 42.2 months |
| all deaths | 512 (34%) | 600 (40%) |
| cardiovascular deaths | 438 (29%) | 534 (35%) |
| of which sudden cardiac death | 218 (14%) | 262 (17%) |
| of which heart failure | 168 (11%) | 197 (13%) |
| other deaths | 74 (5%) | 66 (4%) |
Comparable values could also be recorded in both groups with regard to concomitant diseases, concomitant medication and ECG findings.
discussion
The relevance of the COMET results is controversial to this day, as the metoprolol was administered in a lower dose and with a different galenic formula than is the case with today's standard therapy for heart failure. Critics accuse the heads of the study, financed by the Carvedilol providers Hoffmann-La Roche and GlaxoSmithKline, that it should have been discontinued in 1999 at the latest because of these findings. In the current guidelines for the treatment of heart failure in Europe and the USA, the beta blockers bisoprolol, carvedilol and metoprolol are presumably considered to be equivalent in adequate doses.
The rate of side effects tended to be lower with treatment with carvedilol. The main side effects in both groups were bradycardia and hypotension .