Cardiovascular Drugs and Therapy

, Volume 18, Issue 1, pp 57–66 | Cite as

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)

  • Willem J. Remme
  • Guenter Riegger
  • Per Hildebrandt
  • Michel Komajda
  • Wybren Jaarsma
  • Marco Bobbio
  • Jordi Soler-Soler
  • Armin Scherhag
  • Beatrix Lutiger
  • Lars Rydén


Aims: Heart failure (HF) treatment guidelines of the ESC recommend ACE-inhibitors (ACE-I) as first-line treatment and β-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 β-blockade should not be delayed.

carvedilol ACE inhibition heart failure ventricular remodelling guidelines echocardiography first-line therapy combined treatment monotherapy CARMEN randomised controlled trial 


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Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Willem J. Remme
    • 1
  • Guenter Riegger
    • 2
  • Per Hildebrandt
    • 3
  • Michel Komajda
    • 4
  • Wybren Jaarsma
    • 5
  • Marco Bobbio
    • 6
  • Jordi Soler-Soler
    • 7
  • Armin Scherhag
    • 8
  • Beatrix Lutiger
    • 8
  • Lars Rydén
    • 9
  1. 1.Sticares FoundationRhoonThe Netherlands
  2. 2.University of RegensburgRegensburgGermany
  3. 3.Frederiksberg HospitalFrederiksbergDenmark
  4. 4.Centre Hospitalier Pitié SalpetrièreParisFrance
  5. 5.St. Antonius HospitalNieuwegeinThe Netherlands
  6. 6.Hospital Le MolinetteTorinoItaly
  7. 7.University Hospital Vall d’HebronBarcelonaSpain
  8. 8.F. Hoffmann-La RocheBaselSwitzerland
  9. 9.Karolinska HospitalStockholmSweden

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