title: Tolerability of carvedilol and ACE-Inhibition in mild heart failure. Results of CARMEN (Carvedilol ACE-Inhibitor Remodelling Mild CHF EvaluatioN).
abstract: BACKGROUND
  Management guidelines for heart failure recommend ACE-I and beta-blockers. The perception of difficult up-titration might have added to the slow uptake of beta-blockers despite their mortality and morbidity benefits.
  
  
  OBJECTIVE
  CARMEN offered a possibility to study safety and tolerability of enalapril against carvedilol and their combination.
  
  
  METHODS
  Five hundred and seventy-two patients were blindly up-titrated on carvedilol (target 25 mg bid) and/or enalapril (target 10 mg bid), and continued for 18 months. In the combination arm, carvedilol was up-titrated before enalapril.
  
  
  RESULTS
  There was no group related difference in adverse events during up-titration. Withdrawal rates were 31, 30 and 30%, and serious adverse events 28, 29 and 34% in the combination, carvedilol and enalapril arms. Mortality was similar in all groups (all-cause N=14, 14 and 14; cardiovascular N=9, 13 and 14). All-cause and cardiovascular hospitalizations occurred in 26, 27 and 32%, and in 12, 16 and 22% in the combination, carvedilol and enalapril arms, respectively.
  
  
  CONCLUSIONS
  The safety profile was similar in all treatment arms. In contrast to common perception, there was no difference in tolerability between the ACE-I and carvedilol. This result is even more remarkable as the high prestudy use of ACE-I (65%) might have introduced a bias by selecting ACE-I tolerant patients, who were only switched from their former ACE-I to enalapril.
authors.affiliation: Institut de Cardiologie, Centre Hospitalier GH Pitié-Salpêtrière, 47-83 Bld de l'Hôpital, 75013, Paris Cedex 13, France. Veronique.villareal@chups.jusssieu.fr
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.forename: Beatrix
authors.initials: B
authors.lastname: Lutiger
authors.forename: Hugo
authors.initials: H
authors.lastname: Madeira
authors.forename: Kristian
authors.initials: K
authors.lastname: Thygesen
authors.forename: Marco
authors.initials: M
authors.lastname: Bobbio
authors.forename: Per
authors.initials: P
authors.lastname: Hildebrandt
authors.forename: Wybren
authors.initials: W
authors.lastname: Jaarsma
authors.forename: Günter
authors.initials: G
authors.lastname: Riegger
authors.forename: Lars
authors.initials: L
authors.lastname: Rydén
authors.forename: Armin
authors.initials: A
authors.lastname: Scherhag
authors.forename: Jordi
authors.initials: J
authors.lastname: Soler-Soler
authors.forename: Willem J
authors.initials: WJ
authors.lastname: Remme
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006760:Hospitalization; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000187:drug effects*; D028761:Withholding Treatment
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D004656:Enalapril; D003404:Creatinine