The benefits of early combination treatment of carvedilol and an ACE-inhibitor in mild heart failure and left ventricular systolic dysfunction. The carvedilol and ACE-inhibitor remodelling mild heart failure evaluation trial (CARMEN).

Abstract

AIMS:

Heart failure (HF) treatment guidelines of the ESC recommend ACE-inhibitors (ACE-I) as first-line treatment and beta-blockers added if patients remain symptomatic. CARMEN explored the need for combined treatment for remodelling and order of introduction by comparing the ACE-I enalapril against carvedilol and their combination.

METHODS:

In a parallel-group, 3-arm study of 18 months duration, 572 mild heart failure patients were randomly assigned to carvedilol (N = 191), enalapril (N = 190) or their combination (N = 191). In the latter, carvedilol was up-titrated before enalapril. Left ventricular (LV) remodelling was assessed by transthoracic echocardiography (biplane, modified Simpson) at baseline and after 6, 12 and 18 months of maintenance therapy. Primary comparisons considered the change in LV end-systolic volume index (LVESVI) from baseline to month 18 between the combination and enalapril, and between carvedilol and enalapril.

RESULTS:

In the first primary comparison, LVESVI was reduced by 5.4 ml/m2 (p = 0.0015) in favour of combination therapy compared to enalapril. The second primary comparison tended to favour carvedilol to enalapril (NS). In the within treatment arm analyses, carvedilol significantly reduced LVESVI by 2.8 ml/m2 (p = 0.018) compared to baseline, whereas enalapril did not. LVESVI decreased by 6.3 ml/m2 (p = 0.0001) with combination therapy. All three arms showed similar safety profiles and withdrawal rates.

CONCLUSION:

CARMEN is the first study to demonstrate that early combination of ACE-I and carvedilol reverses LV remodelling in patients with mild to moderate HF and LV systolic dysfunction. The results of the CARMEN study support a therapeutic strategy in which the institution of beta-blockade should not be delayed.

• Authors: Willem J Remme, Guenter Riegger, Per Hildebrandt, Michel Komajda, Wybren Jaarsma, Marco Bobbio, Jordi Soler-Soler, Armin Scherhag, Beatrix Lutiger, Lars Rydén
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 18 Issue 1 Pg. 57-66 (Jan 2004) ISSN: 0920-3206 [Print] United States
• PMID: 15115904 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Carbazoles
• Propanolamines
• Carvedilol
• Enalapril

Topics

• Adrenergic beta-Antagonists (administration & dosage, therapeutic use)
• Adult
• Aged
• Aged, 80 and over
• Angiotensin-Converting Enzyme Inhibitors (administration & dosage, therapeutic use)
• Carbazoles (administration & dosage, therapeutic use)
• Carvedilol
• Chronic Disease
• Double-Blind Method
• Drug Therapy, Combination
• Enalapril (administration & dosage, therapeutic use)
• Female
• Heart Failure (drug therapy, physiopathology)
• Humans
• Male
• Middle Aged
• Propanolamines (administration & dosage, therapeutic use)
• Ventricular Remodeling (drug effects)