title: Effect of Carvedilol, Ivabradine or their combination on exercise capacity in patients with Heart Failure (the CARVIVA HF trial).
abstract: OBJECTIVE
  Patients with heart failure (HF) have reduced exercise capacity. The beneficial effect of beta-blocker on prognosis is not matched by an impact on exercise capacity and quality of life. We performed a randomised open blinded endpoint study to assess the effect of heart rate reduction with carvedilol, ivabradine, and their combination on exercise capacity in HF patients receiving maximal dose of ACE inhibitor.
  
  
  RESULTS
  After a run-in phase patients were randomly allocated to 3 groups: carvedilol up to 25mg bid (n=38); ivabradine up to 7.5mg bid (n=41); and carvedilol/ivabradine up to 12.5/7.5mg bid (n=42). The maximal dose of study treatment was more frequently tolerated in patients receiving ivabradine (36/41) than in those receiving carvedilol (18/38) or combination therapy (32/42) (P<0.01 ivabradine versus carvedilol). Heart rate was reduced in all three groups, but to a greater extent by the combination. The distance walked on the 6-min walking test and the exercise time on MVO(2) test significantly improved in the ivabradine and combination groups (both P<0.01 versus baseline), as did peak VO(2) and VAT (P<0.01 for ivabradine and P<0.03 for combination versus carvedilol, respectively). No changes in these parameters were found with carvedilol. The patients receiving ivabradine or the combination had better quality of life (P<0.01 versus baseline for ivabradine and P<0.02 for combination), versus no change with carvedilol.
  
  
  CONCLUSIONS
  Ivabradine alone or in combination with carvedilol is more effective than carvedilol alone at improving exercise tolerance and quality of life in HF patients.
authors.affiliation: Department of Medical Sciences, IRCCS San Raffaele Roma, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Volterrani
authors.forename: Gennaro
authors.initials: G
authors.lastname: Cice
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Caminiti
authors.forename: Cristiana
authors.initials: C
authors.lastname: Vitale
authors.forename: Salvatore
authors.initials: S
authors.lastname: D'Isa
authors.forename: Pasquale
authors.initials: P
authors.lastname: Perrone Filardi
authors.forename: Flavio
authors.initials: F
authors.lastname: Acquistapace
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marazzi
authors.forename: Massimo
authors.initials: M
authors.lastname: Fini
authors.forename: Giuseppe M C
authors.initials: GM
authors.lastname: Rosano
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D001552:Benzazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D002227:Carbazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D000077261:Carvedilol; D054815:Cyclic Nucleotide-Gated Cation Channels; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D000077550:Ivabradine; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D011788:Quality of Life; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D002227:Carbazoles; D054815:Cyclic Nucleotide-Gated Cation Channels; D011412:Propanolamines; D000077261:Carvedilol; D000077550:Ivabradine