title: Addition of ivabradine to β-blocker improves exercise capacity in systolic heart failure patients in a prospective, open-label study.
abstract: BACKGROUND
  Difficulties initiating and uptitrating β-blockers due to tolerability can complicate management of heart failure. Among other actions, β-blockers reduce heart rate, which is an important cardiovascular risk factor in heart failure. A new therapeutic strategy is ivabradine, which reduces resting heart rate and is associated with improved outcomes.
  
  
  METHODS
  A 5-month, prospective, open-label, nonrandomized single-center study was performed in 69 patients. All patients had chronic heart failure with left ventricular systolic dysfunction in sinus rhythm, each were initiated on 3.125 mg twice daily (bid) carvedilol alone (n = 36) or 3.125 mg bid carvedilol/5 mg bid ivabradine (n = 33), on top of background therapy including angiotensin-converting enzyme inhibitor (88%), diuretics (86%), antiplatelet agents (91%), and statins (90%). Dosages were uptitrated every 2 weeks to 25 mg bid carvedilol in both groups and 7.5 mg bid ivabradine maximum in the carvedilol/ivabradine group. Uptitration of carvedilol lasted 1.9 ± 0.4 months with carvedilol/ivabradine and 2.8 ± 0.6 months with carvedilol alone (P < 0.05).
  
  
  RESULTS
  The patients receiving ivabradine had lower resting heart rate at 5 months (61.6 ± 3.1 versus 70.2 ± 4.4 bpm, P < 0.05). Adding ivabradine to carvedilol in patients with heart failure was associated with increases in the 6-min walk test and ejection fraction (all P < 0.05). Treatment tolerability was satisfactory. Patients receiving ivabradine and carvedilol had lower heart rates and better exercise capacity than those on carvedilol alone.
  
  
  CONCLUSIONS
  Adding ivabradine to carvedilol in patients with chronic heart failure improves the uptitration of β-blocker. The results merit further verification in a prospective double-blind study.
authors.affiliation: Donetsk National Medical University of Maxim Gorky, Illicha Avenue, 16, Donetsk, 83000, Ukraine, bagriyae@mail.ru.
authors.forename: A E
authors.initials: AE
authors.lastname: Bagriy
authors.forename: E V
authors.initials: EV
authors.lastname: Schukina
authors.forename: O V
authors.initials: OV
authors.lastname: Samoilova
authors.forename: O A
authors.initials: OA
authors.lastname: Pricolota
authors.forename: S I
authors.initials: SI
authors.lastname: Malovichko
authors.forename: A V
authors.initials: AV
authors.lastname: Pricolota
authors.forename: E A
authors.initials: EA
authors.lastname: Bagriy
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D001552:Benzazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D002227:Carbazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077261:Carvedilol; D004359:Drug Therapy, Combination; D015444:Exercise; D017079:Exercise Tolerance; D005260:Female; D054143:Heart Failure, Systolic / Q000188:drug therapy*; D006339:Heart Rate; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D012307:Risk Factors; D018487:Ventricular Dysfunction, Left
chemical_list: D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D002227:Carbazoles; D002317:Cardiovascular Agents; D011412:Propanolamines; D000077261:Carvedilol; D000077550:Ivabradine