Skip to main content
Top
Published in: Cardiology and Therapy 1-2/2014

Open Access 01-12-2014 | Original Research

Ivabradine Versus Beta-Blockers in Patients with Conduction Abnormalities or Left Ventricular Dysfunction Undergoing Cardiac Surgery

Authors: Luminita Iliuta, Marius Rac-Albu

Published in: Cardiology and Therapy | Issue 1-2/2014

Login to get access

Abstract

Introduction

In patients with conduction abnormalities or left ventricle (LV) dysfunction the use of β-blockers for post cardiac surgery rhythm control is difficult and controversial, with a paucity of information about other drugs such ivabradine used postoperatively. The objective of this study was to compare the efficacy and safety of ivabradine versus metoprolol used perioperatively in cardiac surgery patients with conduction abnormalities or LV systolic dysfunction.

Methods

This was an open-label, randomized clinical trial enrolling 527 patients with conduction abnormalities or LV systolic dysfunction undergoing coronary artery bypass grafting or valvular replacement, randomized to take ivabradine or metoprolol, or metoprolol plus ivabradine. The primary endpoints were the composites of 30-day mortality, in-hospital atrial fibrillation (AF), in-hospital three-degree atrioventricular block and need for pacing, in-hospital worsening heart failure (HF; safety endpoints), duration of hospital stay and immobilization and the above endpoint plus in-hospital bradycardia, gastrointestinal symptoms, sleep disturbances, cold extremities (efficacy plus safety endpoint).

Results

Heart rate reduction and prevention of postoperative AF or tachyarrhythmia with combined therapy was more effective than with metoprolol or ivabradine alone during the immediate postoperative management of cardiac surgery patients. In the Ivabradine group, the frequency of early postoperative pacing and HF worsening was smaller than in the Metoprolol group and in combined therapy group. The frequency of primary combined endpoint was lower in the combined Ivabradine + Metoprolol group compared with the monotherapy groups.

Conclusion

Considering efficacy and safety, the cardiac rhythm reduction after open heart surgery in patients with conduction abnormalities or LV dysfunction with ivabradine plus metoprolol emerged as the best treatment in this trial.
Appendix
Available only for authorised users
Literature
1.
go back to reference Mina K, Chung MD. Cardiac surgery: postoperative arrhythmias. Crit Care Med. 2000;28(10 Suppl):N136–44. Mina K, Chung MD. Cardiac surgery: postoperative arrhythmias. Crit Care Med. 2000;28(10 Suppl):N136–44.
2.
go back to reference Helgadottir S, Sigurdsson MI, Ingvarsdottir IL, Arnar DO, Gudbjartsson T. Atrial fibrillation following cardiac surgery: risk analysis and long-term survival. J Cardiothorac Surg. 2012;7:87.PubMedCentralPubMedCrossRef Helgadottir S, Sigurdsson MI, Ingvarsdottir IL, Arnar DO, Gudbjartsson T. Atrial fibrillation following cardiac surgery: risk analysis and long-term survival. J Cardiothorac Surg. 2012;7:87.PubMedCentralPubMedCrossRef
3.
go back to reference Taylor G, Malik S, Colliver J, et al. Usefulness of AF as a predictor of stroke after isolated coronary artery bypass grafting. Am J Cardiol. 1987;60:905–7.PubMedCrossRef Taylor G, Malik S, Colliver J, et al. Usefulness of AF as a predictor of stroke after isolated coronary artery bypass grafting. Am J Cardiol. 1987;60:905–7.PubMedCrossRef
4.
go back to reference Zaman AG, Archbold RA, Helft G, Paul EA, Curzen NP, Mills PG. AF after coronary artery bypass surgery: a model for preoperative risk stratification. Circulation. 2000;101:1403–8.PubMedCrossRef Zaman AG, Archbold RA, Helft G, Paul EA, Curzen NP, Mills PG. AF after coronary artery bypass surgery: a model for preoperative risk stratification. Circulation. 2000;101:1403–8.PubMedCrossRef
5.
go back to reference Auer J, Weber T, Berent R, et al. Risk factors of postoperative atrial fibrillation after cardiac surgery. J Card Surg. 2005;20(5):425–31.PubMedCrossRef Auer J, Weber T, Berent R, et al. Risk factors of postoperative atrial fibrillation after cardiac surgery. J Card Surg. 2005;20(5):425–31.PubMedCrossRef
6.
go back to reference Mathew JP, Fontes ML, Tudor IC, et al. AF after coronary artery surgery—a multicenter risk index for AF after cardiac Surgery. Am Heart J. 2004;147:636–43.CrossRef Mathew JP, Fontes ML, Tudor IC, et al. AF after coronary artery surgery—a multicenter risk index for AF after cardiac Surgery. Am Heart J. 2004;147:636–43.CrossRef
7.
go back to reference Stebbins D, Igidbashian L, Goldman SM, et al. Clinical outcome of patients who develop AF after coronary artery bypass graft surgery. PACE. 1995;18:798. Stebbins D, Igidbashian L, Goldman SM, et al. Clinical outcome of patients who develop AF after coronary artery bypass graft surgery. PACE. 1995;18:798.
8.
go back to reference Mathew JP, Parks R, Savino JS, et al. AF following coronary artery bypass graft surgery: predictors, outcomes, and resource utilization. JAMA. 1996;276:300–6.PubMedCrossRef Mathew JP, Parks R, Savino JS, et al. AF following coronary artery bypass graft surgery: predictors, outcomes, and resource utilization. JAMA. 1996;276:300–6.PubMedCrossRef
9.
go back to reference Camm AJ, Kirchhof P, Lip GYH, et al. Guidelines for the management of AF. Eur Heart J. 2010;31:2369–429.PubMedCrossRef Camm AJ, Kirchhof P, Lip GYH, et al. Guidelines for the management of AF. Eur Heart J. 2010;31:2369–429.PubMedCrossRef
10.
go back to reference Kaireviciute D, Blann AD, Balakrishnan B, et al. Characterisation and validity of inflammatory biomarkers in the prediction of post-operative AF in coronary artery disease patients. Thromb Haemost. 2010;104:122–7.PubMedCrossRef Kaireviciute D, Blann AD, Balakrishnan B, et al. Characterisation and validity of inflammatory biomarkers in the prediction of post-operative AF in coronary artery disease patients. Thromb Haemost. 2010;104:122–7.PubMedCrossRef
11.
go back to reference Kalman JM, Munawar M, Howes LG, et al. AF after coronary artery bypass grafting is associated with sympathetic activation. Ann Thorac Surg. 1995;60:1709–15.PubMedCrossRef Kalman JM, Munawar M, Howes LG, et al. AF after coronary artery bypass grafting is associated with sympathetic activation. Ann Thorac Surg. 1995;60:1709–15.PubMedCrossRef
12.
go back to reference Kaireviciute D, Aidietis A, Lip GY. AF following cardiac surgery: clinical features and preventative strategies. Eur Heart J. 2009;30:410–25.PubMedCrossRef Kaireviciute D, Aidietis A, Lip GY. AF following cardiac surgery: clinical features and preventative strategies. Eur Heart J. 2009;30:410–25.PubMedCrossRef
13.
go back to reference Mathew JP, Fontes ML, Tudor IC, et al. A multicenter risk index for AF after cardiac surgery. JAMA. 2004;291:1720–9.PubMedCrossRef Mathew JP, Fontes ML, Tudor IC, et al. A multicenter risk index for AF after cardiac surgery. JAMA. 2004;291:1720–9.PubMedCrossRef
14.
go back to reference Aranski SF, ShawDP, Adams DH, Rizzo RJ, Couper GS, VanderVliet M. Predictors of AF after coronary artery surgery. Current trends and impact on hospital resources. Circulation 1996;94:390–7. Aranski SF, ShawDP, Adams DH, Rizzo RJ, Couper GS, VanderVliet M. Predictors of AF after coronary artery surgery. Current trends and impact on hospital resources. Circulation 1996;94:390–7.
15.
go back to reference Ascione R, Caputo M, Calori G, Lloyd CT, Underwood MJ, Angelini GD. Predictors of AF after conventional and beating heart coronary surgery: a prospective, randomized study. Circulation. 2000;102:1530–5. Ascione R, Caputo M, Calori G, Lloyd CT, Underwood MJ, Angelini GD. Predictors of AF after conventional and beating heart coronary surgery: a prospective, randomized study. Circulation. 2000;102:1530–5.
16.
go back to reference Iliuta L, Christodorescu R, Filipescu D, et al. Prevention of perioperative AF with betablockers in coronary surgery: betaxolol versus metoprolol. Interact Cardiov Thorac Surg. 2010;9:89–93.CrossRef Iliuta L, Christodorescu R, Filipescu D, et al. Prevention of perioperative AF with betablockers in coronary surgery: betaxolol versus metoprolol. Interact Cardiov Thorac Surg. 2010;9:89–93.CrossRef
17.
go back to reference Burgess DC, Kilborn MJ, Keech AC. Interventions for prevention of postoperative AF and its complications after cardiac surgery: a meta-analysis. Eur Heart J. 2006;27:2846–57.PubMedCrossRef Burgess DC, Kilborn MJ, Keech AC. Interventions for prevention of postoperative AF and its complications after cardiac surgery: a meta-analysis. Eur Heart J. 2006;27:2846–57.PubMedCrossRef
18.
go back to reference Lucio Ede A, Flores A, Blacher C, et al. Effectiveness of metoprolol in preventing AF and flutter in the postoperative period of coronary artery bypass graft surgery. Arquivos Brasileiros de Cardiologia. 2004;82:42–46; 37–41. Lucio Ede A, Flores A, Blacher C, et al. Effectiveness of metoprolol in preventing AF and flutter in the postoperative period of coronary artery bypass graft surgery. Arquivos Brasileiros de Cardiologia. 2004;82:42–46; 37–41.
19.
go back to reference Matangi MF, Neutze JM, Graham KJ, et al. Arrhythmia prophylaxis after aorto-coronary bypass: the effect of minidose propanolol. J Thorac Cardiov Sur. 1985;89:439–43. Matangi MF, Neutze JM, Graham KJ, et al. Arrhythmia prophylaxis after aorto-coronary bypass: the effect of minidose propanolol. J Thorac Cardiov Sur. 1985;89:439–43.
20.
go back to reference Crystal E, Garfinkle MS, Connolly SS, et al.: Interventions for preventing post-operative AF in patients undergoing heart surgery. Cochrane Database Syst Rev. 2004(4), Art. No.CD003611. Crystal E, Garfinkle MS, Connolly SS, et al.: Interventions for preventing post-operative AF in patients undergoing heart surgery. Cochrane Database Syst Rev. 2004(4), Art. No.CD003611.
21.
go back to reference Crystal E, Thorpe KE, Connolly SJ, et al. Metoprolol prophylaxis against postoperative AF increases length of hospital stay in patients not on preoperative β-blockers: the beta blocker length of stay (BLOS) trial. Heart. 2004;90:941–2.PubMedCentralPubMedCrossRef Crystal E, Thorpe KE, Connolly SJ, et al. Metoprolol prophylaxis against postoperative AF increases length of hospital stay in patients not on preoperative β-blockers: the beta blocker length of stay (BLOS) trial. Heart. 2004;90:941–2.PubMedCentralPubMedCrossRef
22.
go back to reference Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation. 2004;110:340–437.CrossRef Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation. 2004;110:340–437.CrossRef
23.
go back to reference Swedberg K, Komajda M, Böhm M, et al. SHIFT Investigators: Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;9744:875–85.CrossRef Swedberg K, Komajda M, Böhm M, et al. SHIFT Investigators: Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;9744:875–85.CrossRef
24.
go back to reference Fox K, Ford I, Steg PG, BEAUTIFUL Investigators, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;9641:807–16.CrossRef Fox K, Ford I, Steg PG, BEAUTIFUL Investigators, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;9641:807–16.CrossRef
25.
go back to reference Iliuta L, Enache R. Ivabradine versus beta-blockers in patients with conduction abnormalities or left ventricular dysfunction undergoing coronary artery bypass grafting. InTech Publishing. 2011, p. 355–368. Iliuta L, Enache R. Ivabradine versus beta-blockers in patients with conduction abnormalities or left ventricular dysfunction undergoing coronary artery bypass grafting. InTech Publishing. 2011, p. 355–368.
26.
go back to reference Yue-Chun L, Teng Z, Na-Dan Z, Li-Sha G, Qin L, Xue-Qiang G, Jia-Feng L. Comparison of effects of ivabradine versus carvedilol in murine model with the Coxsackievirus B3-induced viral myocarditis. PLoS ONE. 2012;7:e39394.PubMedCentralPubMedCrossRef Yue-Chun L, Teng Z, Na-Dan Z, Li-Sha G, Qin L, Xue-Qiang G, Jia-Feng L. Comparison of effects of ivabradine versus carvedilol in murine model with the Coxsackievirus B3-induced viral myocarditis. PLoS ONE. 2012;7:e39394.PubMedCentralPubMedCrossRef
27.
go back to reference Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001;33:337–43.PubMedCrossRef Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001;33:337–43.PubMedCrossRef
28.
go back to reference Villareal RP, Hariharan R, Liu B, et al. Postoperative AF and mortality after coronary artery bypass surgery. J Am Coll Cardiol. 2004;43:742–8.PubMedCrossRef Villareal RP, Hariharan R, Liu B, et al. Postoperative AF and mortality after coronary artery bypass surgery. J Am Coll Cardiol. 2004;43:742–8.PubMedCrossRef
29.
go back to reference Tamis JE, Steinberg JS. AF independently prolongs hospital stay after coronary artery bypass surgery. Clin Cardiol. 2000;23:155–9.PubMedCrossRef Tamis JE, Steinberg JS. AF independently prolongs hospital stay after coronary artery bypass surgery. Clin Cardiol. 2000;23:155–9.PubMedCrossRef
30.
go back to reference Reed G III, Singer DE, Picard EH, DeSanctis RW. Stroke following coronary-artery bypass surgery. A case-control estimate of the risk from carotid bruits. New Engl J Med. 1988;319:1246–50. Reed G III, Singer DE, Picard EH, DeSanctis RW. Stroke following coronary-artery bypass surgery. A case-control estimate of the risk from carotid bruits. New Engl J Med. 1988;319:1246–50.
31.
go back to reference Martinez EA, Bass EB, Zimetbaum P. Pharmacologic control of rhythm: American College of Chest Physicians guidelines for the prevention and management of postoperative AF after cardiac surgery. Chest. 2005;128(2 Suppl):48S–55S.PubMedCrossRef Martinez EA, Bass EB, Zimetbaum P. Pharmacologic control of rhythm: American College of Chest Physicians guidelines for the prevention and management of postoperative AF after cardiac surgery. Chest. 2005;128(2 Suppl):48S–55S.PubMedCrossRef
32.
go back to reference Lamb RK, Prabhakar G, Thorpe JA, et al. The use of atenolol in the prevention of supraventricular arrhythmias following coronary artery surgery. Eur Heart J. 1988;9:32–36. Lamb RK, Prabhakar G, Thorpe JA, et al. The use of atenolol in the prevention of supraventricular arrhythmias following coronary artery surgery. Eur Heart J. 1988;9:32–36.
33.
go back to reference Kamei M, Morita S, Hayashi Y, et al. Carvedilol versus metoprolol for the prevention of AF after off-pump coronary bypass surgery: rationale and design of the carvedilol or metoprolol post-revascularization AF controlled trial (COMPACT). Cardiovasc Drug Ther. 2006;20:219–27.CrossRef Kamei M, Morita S, Hayashi Y, et al. Carvedilol versus metoprolol for the prevention of AF after off-pump coronary bypass surgery: rationale and design of the carvedilol or metoprolol post-revascularization AF controlled trial (COMPACT). Cardiovasc Drug Ther. 2006;20:219–27.CrossRef
34.
go back to reference Celik T, Iyisoy A, Jata B, et al. Betablockers for the prevention of AF after coronary artery bypass surgery: carvedilol versus metoprolol. Int J Cardiol. 2009;135:393–6.PubMedCrossRef Celik T, Iyisoy A, Jata B, et al. Betablockers for the prevention of AF after coronary artery bypass surgery: carvedilol versus metoprolol. Int J Cardiol. 2009;135:393–6.PubMedCrossRef
35.
go back to reference Daudon P, Corcos T, Gandjbakhch I, et al. Prevention of AF or flutter by acebutolol after coronary bypass grafting. Am J Cardiol. 1986;58:933–66.PubMedCrossRef Daudon P, Corcos T, Gandjbakhch I, et al. Prevention of AF or flutter by acebutolol after coronary bypass grafting. Am J Cardiol. 1986;58:933–66.PubMedCrossRef
36.
go back to reference White HD, Antman EM, Glynn MA, et al. Efficacy and safety of timolol for prevention of supraventricular tachyarrhythmias after coronary artery bypass surgery. Circulation. 1984;70:479–84.PubMedCrossRef White HD, Antman EM, Glynn MA, et al. Efficacy and safety of timolol for prevention of supraventricular tachyarrhythmias after coronary artery bypass surgery. Circulation. 1984;70:479–84.PubMedCrossRef
37.
go back to reference Sanjuan R, Blasco M, Carbonell N, et al. Preoperative use of sotalol versus atenolol for AF after cardiac surgery. Ann Thorac Surg. 2004;77:838–43.PubMedCrossRef Sanjuan R, Blasco M, Carbonell N, et al. Preoperative use of sotalol versus atenolol for AF after cardiac surgery. Ann Thorac Surg. 2004;77:838–43.PubMedCrossRef
38.
go back to reference Parikka H, Toivonen L, Heikkila L, et al. Comparison of sotalol and metoprolol in the prevention of AF after coronary artery bypass surgery. J Cardiovasc Pharm. 1998;31:67–73.CrossRef Parikka H, Toivonen L, Heikkila L, et al. Comparison of sotalol and metoprolol in the prevention of AF after coronary artery bypass surgery. J Cardiovasc Pharm. 1998;31:67–73.CrossRef
39.
go back to reference Suttorp MJ, Kingma JH, Tjon Joe Gin RM, et al. Efficacy and safety of low- and high-dose sotalol versus propranolol in the prevention of supraventricular tachyarrhythmias early after coronary artery bypass operations. J Thorac Cardiov Surg. 1990;100:921–26. Suttorp MJ, Kingma JH, Tjon Joe Gin RM, et al. Efficacy and safety of low- and high-dose sotalol versus propranolol in the prevention of supraventricular tachyarrhythmias early after coronary artery bypass operations. J Thorac Cardiov Surg. 1990;100:921–26.
40.
go back to reference Bagshaw SM, Galbraith PD, Mitchell LB, et al. Prophylactic amiodarone for prevention of AF after cardiac surgery: a meta-analysis. Ann Thorac Surg. 2006;82:1927–37.PubMedCrossRef Bagshaw SM, Galbraith PD, Mitchell LB, et al. Prophylactic amiodarone for prevention of AF after cardiac surgery: a meta-analysis. Ann Thorac Surg. 2006;82:1927–37.PubMedCrossRef
Metadata
Title
Ivabradine Versus Beta-Blockers in Patients with Conduction Abnormalities or Left Ventricular Dysfunction Undergoing Cardiac Surgery
Authors
Luminita Iliuta
Marius Rac-Albu
Publication date
01-12-2014
Publisher
Springer Healthcare
Published in
Cardiology and Therapy / Issue 1-2/2014
Print ISSN: 2193-8261
Electronic ISSN: 2193-6544
DOI
https://doi.org/10.1007/s40119-013-0024-1

Other articles of this Issue 1-2/2014

Cardiology and Therapy 1-2/2014 Go to the issue