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Published in: American Journal of Cardiovascular Drugs 2/2014

01-04-2014 | Review Article

Beta-Blockers and Ivabradine in Chronic Heart Failure: From Clinical Trials to Clinical Practice

Authors: Antonino Di Franco, Filippo M. Sarullo, Ylenia Salerno, Stefano Figliozzi, Rossella Parrinello, Pietro Di Pasquale, Gaetano A. Lanza

Published in: American Journal of Cardiovascular Drugs | Issue 2/2014

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Abstract

Beta-blockers have become one of the cornerstones of treatment of patients with heart failure (HF) and depressed left ventricular function, but in clinical practice only 30–35 % of patients achieve the therapeutic target dose as established in randomized clinical trials. Moreover, high resting heart rate (HR) has emerged as a simple but relevant risk factor for cardiovascular events, including coronary artery disease and HF; also, it was found to have an independent prognostic value in patients with HF. Evidence that HR could be considered a good parameter to evaluate the quality of treatment in patients with HF has been suggested; of note, many patients maintain a resting HR ≥70 beats per minute despite optimal beta-blocker therapy. In recent years, a new drug able to reduce HR, ivabradine, has been introduced in clinical practice, and its use in the clinical setting of HF patients has been recommended by current European Society of Cardiology (ESC) guidelines. Here we review the evidence of the prognostic role of HR in systolic HF and the potential relationship between HR lowering and the beneficial effects of beta-blockers; we will also analyze the reasons why an appropriate use of these drugs is seldom achieved in clinical practice, and review the evidence for the use of ivabradine in systolic HF in the clinical setting.
Literature
1.
go back to reference McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A; ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. doi:10.1093/eurheartj/ehs104. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A; ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. doi:10.​1093/​eurheartj/​ehs104.
2.
go back to reference Davie AP, Francis CM, Caruana L, Sutherland GR, McMurray JJ. Assessing diagnosis in heart failure: which features are any use? QJM. 1997;90:335–9.PubMedCrossRef Davie AP, Francis CM, Caruana L, Sutherland GR, McMurray JJ. Assessing diagnosis in heart failure: which features are any use? QJM. 1997;90:335–9.PubMedCrossRef
3.
go back to reference Mant J, Doust J, Roalfe A, Barton P, Cowie MR, Glasziou P, Mant D, McManus RJ, Holder R, Deeks J, Fletcher K, Qume M, Sohanpal S, Sanders S, Hobbs FD. Systematic review and individual patient data meta-analysis of diagnosis of heart failure, with modelling of implications of different diagnostic strategies in primary care. Health Technol Assess. 2009;13:1–207.PubMed Mant J, Doust J, Roalfe A, Barton P, Cowie MR, Glasziou P, Mant D, McManus RJ, Holder R, Deeks J, Fletcher K, Qume M, Sohanpal S, Sanders S, Hobbs FD. Systematic review and individual patient data meta-analysis of diagnosis of heart failure, with modelling of implications of different diagnostic strategies in primary care. Health Technol Assess. 2009;13:1–207.PubMed
4.
go back to reference Oudejans I, Mosterd A, Bloemen JA, Valk MJ, van Velzen E, Wielders JP, Zuithoff NP, Rutten FH, Hoes AW. Clinical evaluation of geriatric outpatients with suspected heart failure: value of symptoms, signs, and additional tests. Eur J Heart Fail. 2011;13:518–27.PubMedCrossRef Oudejans I, Mosterd A, Bloemen JA, Valk MJ, van Velzen E, Wielders JP, Zuithoff NP, Rutten FH, Hoes AW. Clinical evaluation of geriatric outpatients with suspected heart failure: value of symptoms, signs, and additional tests. Eur J Heart Fail. 2011;13:518–27.PubMedCrossRef
6.
go back to reference Kelder JC, Cramer MJ, van Wijngaarden J, van Tooren R, Mosterd A, Moons KG, Lammers JW, Cowie MR, Grobbee DE, Hoes AW. The diagnostic value of physical examination and additional testing in primary care patients with suspected heart failure. Circulation. 2011;124:2865–73.PubMedCrossRef Kelder JC, Cramer MJ, van Wijngaarden J, van Tooren R, Mosterd A, Moons KG, Lammers JW, Cowie MR, Grobbee DE, Hoes AW. The diagnostic value of physical examination and additional testing in primary care patients with suspected heart failure. Circulation. 2011;124:2865–73.PubMedCrossRef
7.
go back to reference Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, Camm AJ, Ellinor PT, Gollob M, Hamilton R, Hershberger RE, Judge DP, Le Marec H, McKenna WJ, Schulze-Bahr E, Semsarian C, Towbin JA, Watkins H, Wilde A, Wolpert C, Zipes DP. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm. 2011;8:1308–39.PubMedCrossRef Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, Camm AJ, Ellinor PT, Gollob M, Hamilton R, Hershberger RE, Judge DP, Le Marec H, McKenna WJ, Schulze-Bahr E, Semsarian C, Towbin JA, Watkins H, Wilde A, Wolpert C, Zipes DP. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies: this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm. 2011;8:1308–39.PubMedCrossRef
8.
go back to reference Kannel WB, Kannel C, Paffenbarger RSJR, Cupples LA. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J. 1987;113(6):1489–94.PubMedCrossRef Kannel WB, Kannel C, Paffenbarger RSJR, Cupples LA. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J. 1987;113(6):1489–94.PubMedCrossRef
9.
go back to reference Fox K, Borer JS, Camm AJ, Danchin N, Ferrari R, Lopez Sendon JL, Steg PG, Tardif JC, Tavazzi L, Tendera M. Resting heart rate in cardiovascular disease. J Am Coll Cardiol. 2007;50(9):823–30.PubMedCrossRef Fox K, Borer JS, Camm AJ, Danchin N, Ferrari R, Lopez Sendon JL, Steg PG, Tardif JC, Tavazzi L, Tendera M. Resting heart rate in cardiovascular disease. J Am Coll Cardiol. 2007;50(9):823–30.PubMedCrossRef
10.
go back to reference CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353:9–13. CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353:9–13.
11.
go back to reference Packer M, Fowler MB, Roecker EB, Coats AJ, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Staiger C, Holcslaw TL, Amann-Zalan I, DeMets DL. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002;106:2194–9.PubMedCrossRef Packer M, Fowler MB, Roecker EB, Coats AJ, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Staiger C, Holcslaw TL, Amann-Zalan I, DeMets DL. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002;106:2194–9.PubMedCrossRef
12.
go back to reference MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001–07. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001–07.
13.
go back to reference Hjalmarson A, Goldstein S, Fagerberg B, Wedel H, Waagstein F, Kjekshus J, Wikstrand J, El Allaf D, Vitovec J, Aldershvile J, Halinen M, Dietz R, Neuhaus KL, Janosi A, Thorgeirsson G, Dunselman PH, Gullestad L, Kuch J, Herlitz J, Rickenbacher P, Ball S, Gottlieb S, Deedwania P. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group. JAMA. 2000;283:1295–302.PubMedCrossRef Hjalmarson A, Goldstein S, Fagerberg B, Wedel H, Waagstein F, Kjekshus J, Wikstrand J, El Allaf D, Vitovec J, Aldershvile J, Halinen M, Dietz R, Neuhaus KL, Janosi A, Thorgeirsson G, Dunselman PH, Gullestad L, Kuch J, Herlitz J, Rickenbacher P, Ball S, Gottlieb S, Deedwania P. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group. JAMA. 2000;283:1295–302.PubMedCrossRef
14.
go back to reference Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651–8.PubMedCrossRef Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651–8.PubMedCrossRef
15.
go back to reference Gheorghiade M, Albert NM, Curtis AB, Thomas Heywood J, McBride ML, Inge PJ, Mehra MR, O’Connor CM, Reynolds D, Walsh MN, Yancy CW, Fonarow GC. Medication dosing in outpatients with heart failure after implementation of a practice-based performance improvement intervention: findings from IMPROVE HF. Congest Heart Fail. 2012;18(1):9–17.PubMedCrossRef Gheorghiade M, Albert NM, Curtis AB, Thomas Heywood J, McBride ML, Inge PJ, Mehra MR, O’Connor CM, Reynolds D, Walsh MN, Yancy CW, Fonarow GC. Medication dosing in outpatients with heart failure after implementation of a practice-based performance improvement intervention: findings from IMPROVE HF. Congest Heart Fail. 2012;18(1):9–17.PubMedCrossRef
16.
go back to reference Fox K, Ford I, Steg PG, Tendera M, Ferrari R. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9641):807–16.PubMedCrossRef Fox K, Ford I, Steg PG, Tendera M, Ferrari R. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9641):807–16.PubMedCrossRef
17.
go back to reference Swedberg K, Komajda M, Böhm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376(9744):875–85.PubMedCrossRef Swedberg K, Komajda M, Böhm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376(9744):875–85.PubMedCrossRef
19.
go back to reference Stewart S, Jenkins A, Buchan S, McGuire A, Capewell S, McMurray JJ. The current cost of heart failure to the National Health Service in the UK. Eur J Heart Fail. 2002;4(3):361–71.PubMedCrossRef Stewart S, Jenkins A, Buchan S, McGuire A, Capewell S, McMurray JJ. The current cost of heart failure to the National Health Service in the UK. Eur J Heart Fail. 2002;4(3):361–71.PubMedCrossRef
20.
go back to reference Juenger J, Schellberg D, Kraemer S, Haunstetter A, Zugck C, Herzog W, Haass M. Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables. Heart. 2002;87(3):235–41.PubMedCentralPubMedCrossRef Juenger J, Schellberg D, Kraemer S, Haunstetter A, Zugck C, Herzog W, Haass M. Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables. Heart. 2002;87(3):235–41.PubMedCentralPubMedCrossRef
21.
go back to reference Gorkin L, Norvell NK, Rosen RC, Charles E, Shumaker SA, McIntyre KM, Capone RJ, Kostis J, Niaura R, Woods P. Assessment of quality of life as observed from the baseline data of the studies of left ventricular dysfunction (SOLVD) trial quality-of-life substudy. Am J Cardiol. 1993;71:1069–73.PubMedCrossRef Gorkin L, Norvell NK, Rosen RC, Charles E, Shumaker SA, McIntyre KM, Capone RJ, Kostis J, Niaura R, Woods P. Assessment of quality of life as observed from the baseline data of the studies of left ventricular dysfunction (SOLVD) trial quality-of-life substudy. Am J Cardiol. 1993;71:1069–73.PubMedCrossRef
22.
go back to reference Dracup K, Walden JA, Stevenson LW, Brecht ML. Quality of life in patients with advanced heart failure. J Heart Lung Transpl. 1992;11:273–9. Dracup K, Walden JA, Stevenson LW, Brecht ML. Quality of life in patients with advanced heart failure. J Heart Lung Transpl. 1992;11:273–9.
23.
go back to reference Huikuri HV, Jokinen V, Syvänne M, et al. Heart rate variability and progression of coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 1999;19:1979–85.PubMedCrossRef Huikuri HV, Jokinen V, Syvänne M, et al. Heart rate variability and progression of coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 1999;19:1979–85.PubMedCrossRef
24.
go back to reference Sambuceti G, Marzilli M, Marraccini P, et al. Coronary vasoconstriction during myocardial ischemia induced by rises in metabolic demand in patients with coronary artery disease. Circulation. 1997;95:2652–9.PubMedCrossRef Sambuceti G, Marzilli M, Marraccini P, et al. Coronary vasoconstriction during myocardial ischemia induced by rises in metabolic demand in patients with coronary artery disease. Circulation. 1997;95:2652–9.PubMedCrossRef
25.
go back to reference Thackray SDR, Ghosh JM, Wright GA, et al. The effect of altering heart rate on ventricular function in patients with heart failure treated with beta-blockers. Am Heart J. 2006;152:713.e9–13. Thackray SDR, Ghosh JM, Wright GA, et al. The effect of altering heart rate on ventricular function in patients with heart failure treated with beta-blockers. Am Heart J. 2006;152:713.e9–13.
26.
go back to reference Traub O, Berk BC. Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler Thromb Vasc Biol. 1998;18:677–85.PubMedCrossRef Traub O, Berk BC. Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler Thromb Vasc Biol. 1998;18:677–85.PubMedCrossRef
27.
go back to reference Ekman I, Chassany O, Komajda M, Böhm M, Borer JS, Ford I, Tavazzi L, Swedberg K. Heart rate reduction with ivabradine and health related quality of life in patients with chronic heart failure: results from the SHIFT study. Eur Heart J. 2011;32(19):2395–404.PubMedCrossRef Ekman I, Chassany O, Komajda M, Böhm M, Borer JS, Ford I, Tavazzi L, Swedberg K. Heart rate reduction with ivabradine and health related quality of life in patients with chronic heart failure: results from the SHIFT study. Eur Heart J. 2011;32(19):2395–404.PubMedCrossRef
28.
go back to reference Diaz A, Bourassa MG, Guertin MC, Tardif JC. Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease. Eur Heart J. 2005;26(10):967–74.PubMedCrossRef Diaz A, Bourassa MG, Guertin MC, Tardif JC. Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease. Eur Heart J. 2005;26(10):967–74.PubMedCrossRef
29.
go back to reference Kjekshus J, Gullestad L. Heart rate as a therapeutic target in heart failure. Eur Heart J Suppl. 1999;1(Suppl H):H64–9. Kjekshus J, Gullestad L. Heart rate as a therapeutic target in heart failure. Eur Heart J Suppl. 1999;1(Suppl H):H64–9.
30.
go back to reference Fox K, Ford I, Steg PG, Tendera M, Robertson M. Ferrari R; BEAUTIFUL investigators; Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet. 2008;372(9641):817–21.PubMedCrossRef Fox K, Ford I, Steg PG, Tendera M, Robertson M. Ferrari R; BEAUTIFUL investigators; Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet. 2008;372(9641):817–21.PubMedCrossRef
31.
go back to reference Bristow MR, Kantrowitz NE, Ginsburg R, Fowler MB. β-adrenergic function in heart muscle disease and heart failure. J Mol Cell Cardiol. 1985;17(suppl.2):41–52.PubMedCrossRef Bristow MR, Kantrowitz NE, Ginsburg R, Fowler MB. β-adrenergic function in heart muscle disease and heart failure. J Mol Cell Cardiol. 1985;17(suppl.2):41–52.PubMedCrossRef
32.
go back to reference Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984;311:819–23.PubMedCrossRef Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984;311:819–23.PubMedCrossRef
33.
go back to reference Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):1495–539.CrossRef Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):1495–539.CrossRef
34.
go back to reference Lanza GA, Fox K, Crea F. Heart rate: a risk factor for cardiac diseases and outcomes? Pathophysiology of cardiac diseases and the potential role of heart rate slowing. Adv Cardiol. 2006;43:1–16.PubMedCrossRef Lanza GA, Fox K, Crea F. Heart rate: a risk factor for cardiac diseases and outcomes? Pathophysiology of cardiac diseases and the potential role of heart rate slowing. Adv Cardiol. 2006;43:1–16.PubMedCrossRef
35.
go back to reference Willenheimer R, van Veldhuisen DJ, Silke B, Erdmann E, Follath F, Krum H, et al. CIBIS III Investigators. Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence: results of the randomized cardiac insufficiency bisoprolol study (CIBIS) III. Circulation. 2005;112(16):2426–35.PubMedCrossRef Willenheimer R, van Veldhuisen DJ, Silke B, Erdmann E, Follath F, Krum H, et al. CIBIS III Investigators. Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence: results of the randomized cardiac insufficiency bisoprolol study (CIBIS) III. Circulation. 2005;112(16):2426–35.PubMedCrossRef
36.
go back to reference Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Circulation. 1996;94(11):2807–16.PubMedCrossRef Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Circulation. 1996;94(11):2807–16.PubMedCrossRef
37.
go back to reference Colucci WS, Kolias TJ, Kirkwood FA, Adams KF, Armstrong WF, Ghali JK, Gottlieb SS, et al. REVERT Study Group. Metoprolol reverses left ventricular remodeling in patients with asymptomatic systolic dysfunction: the REversal of VEntricular Remodeling with toprol-XL (REVERT) trial. Circulation. 2007;116(1):49–56.PubMedCrossRef Colucci WS, Kolias TJ, Kirkwood FA, Adams KF, Armstrong WF, Ghali JK, Gottlieb SS, et al. REVERT Study Group. Metoprolol reverses left ventricular remodeling in patients with asymptomatic systolic dysfunction: the REversal of VEntricular Remodeling with toprol-XL (REVERT) trial. Circulation. 2007;116(1):49–56.PubMedCrossRef
38.
go back to reference Fiuzat M, Wojdyla D, Kitzman D, Fleg J, Keteyian SJ, Kraus WE, et al. Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction: results from the HF-ACTION (Heart Failure: a Controlled Trial Investigating Outcomes of Exercise Training) trial. J Am Coll Cardiol. 2012;60:208–15.PubMedCentralPubMedCrossRef Fiuzat M, Wojdyla D, Kitzman D, Fleg J, Keteyian SJ, Kraus WE, et al. Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction: results from the HF-ACTION (Heart Failure: a Controlled Trial Investigating Outcomes of Exercise Training) trial. J Am Coll Cardiol. 2012;60:208–15.PubMedCentralPubMedCrossRef
39.
go back to reference McAlister FA, Wiebe N, Ezekowitz JA, Leung AA, Armstrong PW. Meta-analysis: beta-blocker dose, heart rate reduction, and death in patients with heart failure. Ann Intern Med. 2009;150(11):784–94.PubMedCrossRef McAlister FA, Wiebe N, Ezekowitz JA, Leung AA, Armstrong PW. Meta-analysis: beta-blocker dose, heart rate reduction, and death in patients with heart failure. Ann Intern Med. 2009;150(11):784–94.PubMedCrossRef
40.
go back to reference Flannery G, Gehrig-Mills R, Billah B, Krum H. Analysis of randomized controlled trials on the effect of magnitude of heart rate reduction on clinical outcomes in patients with systolic chronic heart failure receiving beta-blockers. Am J Cardiol. 2008;101(6):865–9.PubMedCrossRef Flannery G, Gehrig-Mills R, Billah B, Krum H. Analysis of randomized controlled trials on the effect of magnitude of heart rate reduction on clinical outcomes in patients with systolic chronic heart failure receiving beta-blockers. Am J Cardiol. 2008;101(6):865–9.PubMedCrossRef
41.
go back to reference Franciosa JA. The potential role of community-based registries to complement the limited applicability of clinical trial results to the community setting: heart failure as an example. Am J Manag Care. 2004;10:487–92.PubMed Franciosa JA. The potential role of community-based registries to complement the limited applicability of clinical trial results to the community setting: heart failure as an example. Am J Manag Care. 2004;10:487–92.PubMed
42.
go back to reference Stafford RS, Radley DC. The underutilization of cardiac medications of proven benefit, 1990 to 2002. J Am Coll Cardiol. 2003;41:56–61.PubMedCrossRef Stafford RS, Radley DC. The underutilization of cardiac medications of proven benefit, 1990 to 2002. J Am Coll Cardiol. 2003;41:56–61.PubMedCrossRef
43.
go back to reference Gupta R, Tang WH, Young JB. Patterns of beta-blocker utilization in patients with chronic heart failure: experience from a specialized outpatient heart failure clinic. Am Heart J. 2004;147:79–83.PubMedCrossRef Gupta R, Tang WH, Young JB. Patterns of beta-blocker utilization in patients with chronic heart failure: experience from a specialized outpatient heart failure clinic. Am Heart J. 2004;147:79–83.PubMedCrossRef
44.
go back to reference Maggioni AP, Sinagra G, Opasich C, Geraci E, Gorini M, Gronda E, Lucci D, Tognoni G, Balli E, Tavazzi L. Treatment of chronic heart failure with beta adrenergic blockade beyond controlled clinical trials: the BRING-UP experience. Heart. 2003;89:299–305.PubMedCentralPubMedCrossRef Maggioni AP, Sinagra G, Opasich C, Geraci E, Gorini M, Gronda E, Lucci D, Tognoni G, Balli E, Tavazzi L. Treatment of chronic heart failure with beta adrenergic blockade beyond controlled clinical trials: the BRING-UP experience. Heart. 2003;89:299–305.PubMedCentralPubMedCrossRef
45.
go back to reference Mehta PA, McDonagh S, Poole-Wilson PA, Grocott-Mason R, Dubrey SW. Heart failure in a district general hospital: are target doses of beta-blockers realistic? Q J Med. 2004;97:133–9.CrossRef Mehta PA, McDonagh S, Poole-Wilson PA, Grocott-Mason R, Dubrey SW. Heart failure in a district general hospital: are target doses of beta-blockers realistic? Q J Med. 2004;97:133–9.CrossRef
46.
go back to reference Young D, McGuire M. Few CHF patients achieve target dosages of beta blockers, risking hospitalizations and death. Formulary. 2002;37:321. Young D, McGuire M. Few CHF patients achieve target dosages of beta blockers, risking hospitalizations and death. Formulary. 2002;37:321.
47.
go back to reference Kawashiro N, Kasanuki H, Ogawa H, Matsuda N, Hagiwara N, Heart Institute of Japan–Department of Cardiology (HIJC) Investigators. Clinical characteristics and outcome of hospitalized patients with congestive heart failure: results of the HIJC-HF registry. Circ J. 2008;72(12):2015–20.PubMedCrossRef Kawashiro N, Kasanuki H, Ogawa H, Matsuda N, Hagiwara N, Heart Institute of Japan–Department of Cardiology (HIJC) Investigators. Clinical characteristics and outcome of hospitalized patients with congestive heart failure: results of the HIJC-HF registry. Circ J. 2008;72(12):2015–20.PubMedCrossRef
48.
go back to reference Maggioni AP, Dahlström U, Filippatos G, Chioncel O, Leiro MC, Drozdz J, Fruhwald F, Gullestad L, Logeart D, Metra M, Parissis J, Persson H, Ponikowski P, Rauchhaus M, Voors A, Nielsen OW, Zannad F, Tavazzi L. Heart Failure Association of ESC (HFA). EURObservational Research Programme: the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail. 2010;12(10):1076–84.PubMedCrossRef Maggioni AP, Dahlström U, Filippatos G, Chioncel O, Leiro MC, Drozdz J, Fruhwald F, Gullestad L, Logeart D, Metra M, Parissis J, Persson H, Ponikowski P, Rauchhaus M, Voors A, Nielsen OW, Zannad F, Tavazzi L. Heart Failure Association of ESC (HFA). EURObservational Research Programme: the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail. 2010;12(10):1076–84.PubMedCrossRef
49.
go back to reference Fonarow GC, Yancy CW, Albert NM, Curtis AB, Stough WG, Gheorghiade M, Heywood JT, Mehra M, O’Connor CM, Reynolds D, Walsh MN. Improving the use of evidence-based heart failure therapies in the outpatient setting: the IMPROVE HF performance improvement registry. Am Heart J. 2007;154:12–38.PubMedCrossRef Fonarow GC, Yancy CW, Albert NM, Curtis AB, Stough WG, Gheorghiade M, Heywood JT, Mehra M, O’Connor CM, Reynolds D, Walsh MN. Improving the use of evidence-based heart failure therapies in the outpatient setting: the IMPROVE HF performance improvement registry. Am Heart J. 2007;154:12–38.PubMedCrossRef
50.
go back to reference Fowler MB, Lottes SR, Nelson JJ, Lukas MA, Gilbert EM, Greenberg B, Massie BM, Abraham WT, Franciosa JA. Beta-blocker dosing in community-based treatment of heart failure. Am Heart J. 2007;153:1029–36.PubMedCrossRef Fowler MB, Lottes SR, Nelson JJ, Lukas MA, Gilbert EM, Greenberg B, Massie BM, Abraham WT, Franciosa JA. Beta-blocker dosing in community-based treatment of heart failure. Am Heart J. 2007;153:1029–36.PubMedCrossRef
51.
go back to reference Arnold SV, Spertus JA, Masoudi FA, Daugherty SL, Maddox TM, Li Y, Dodson JA, Chan PS. Beyond medication prescription as performance measures: optimal secondary prevention medication dosing after AMI. J Am Coll Cardiol. 2013. doi:10.1016/j.jacc.2013.04.102. [Epub ahead of print]. Arnold SV, Spertus JA, Masoudi FA, Daugherty SL, Maddox TM, Li Y, Dodson JA, Chan PS. Beyond medication prescription as performance measures: optimal secondary prevention medication dosing after AMI. J Am Coll Cardiol. 2013. doi:10.​1016/​j.​jacc.​2013.​04.​102. [Epub ahead of print].
53.
go back to reference Salem SA, McDevitt DG. Central effects of beta-adrenoceptor antagonists. Clin Pharmacol Ther. 1983;33(1):52–7.PubMedCrossRef Salem SA, McDevitt DG. Central effects of beta-adrenoceptor antagonists. Clin Pharmacol Ther. 1983;33(1):52–7.PubMedCrossRef
54.
go back to reference Moreno IB, Carlo CH, Pereira-Barretto AC. Optimized treatment and heart rate reduction in chronic heart failure. Arq Bras Cardiol. 2013. pii:S0066-782X2013005000088. [Epub ahead of print]. Moreno IB, Carlo CH, Pereira-Barretto AC. Optimized treatment and heart rate reduction in chronic heart failure. Arq Bras Cardiol. 2013. pii:S0066-782X2013005000088. [Epub ahead of print].
55.
go back to reference Komajda M, Lapuerta P, Hermans N, Gonzalez-Juanatey JR, van Veldhuisen DJ, Erdmann E, et al. Adherence to guidelines is a predictor of outcome in chronic heart failure: the MAHLER survey. Eur Heart J. 2005;26(16):1653–9.PubMedCrossRef Komajda M, Lapuerta P, Hermans N, Gonzalez-Juanatey JR, van Veldhuisen DJ, Erdmann E, et al. Adherence to guidelines is a predictor of outcome in chronic heart failure: the MAHLER survey. Eur Heart J. 2005;26(16):1653–9.PubMedCrossRef
56.
go back to reference Nieminen MS, Brutsaert D, Dickstein K, Drexler H, Follath F, Harjola VP, et al. EuroHeart Survey Investigators; Heart Failure Association, European Society of Cardiology. EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population. Eur Heart J. 2006;27(22):2725–36.PubMedCrossRef Nieminen MS, Brutsaert D, Dickstein K, Drexler H, Follath F, Harjola VP, et al. EuroHeart Survey Investigators; Heart Failure Association, European Society of Cardiology. EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population. Eur Heart J. 2006;27(22):2725–36.PubMedCrossRef
57.
go back to reference Bucchi A, Baruscotti M, DiFrancesco D. Current-dependent block of rabbit sino-atrial node I(f) channels by ivabradine. J Gen Physiol. 2002;120(1):1–13.PubMedCentralPubMedCrossRef Bucchi A, Baruscotti M, DiFrancesco D. Current-dependent block of rabbit sino-atrial node I(f) channels by ivabradine. J Gen Physiol. 2002;120(1):1–13.PubMedCentralPubMedCrossRef
58.
go back to reference Di Francesco D. I (f) inhibition: a novel mechanism of action. Eur Heart J. 2003;5(suppl G):G19–25.CrossRef Di Francesco D. I (f) inhibition: a novel mechanism of action. Eur Heart J. 2003;5(suppl G):G19–25.CrossRef
59.
go back to reference Fox K, Ford I, Steg PG, Tendera M, Robertson M, Ferrari R. Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet. 2008;372(9641):817–21.PubMedCrossRef Fox K, Ford I, Steg PG, Tendera M, Robertson M, Ferrari R. Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet. 2008;372(9641):817–21.PubMedCrossRef
60.
go back to reference Böhm M, Swedberg K, Komajda M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L. SHIFT Investigators. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet. 2010;376(9744):886–94.PubMedCrossRef Böhm M, Swedberg K, Komajda M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L. SHIFT Investigators. Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial. Lancet. 2010;376(9744):886–94.PubMedCrossRef
61.
go back to reference Swedberg K, Komajda M, Bohm M, Borer J, Robertson M, Tavazzi L, Ford I. Effects on outcomes of heart rate reduction by ivabradine in patients with congestive heart failure: is there an influence of beta-blocker dose? Fndings from the SHIFT (systolic heart failure treatment with the I(f) inhibitor ivabradine trial) Study. J Am Coll Cardiol. 2012;59(22):1938–45.PubMedCrossRef Swedberg K, Komajda M, Bohm M, Borer J, Robertson M, Tavazzi L, Ford I. Effects on outcomes of heart rate reduction by ivabradine in patients with congestive heart failure: is there an influence of beta-blocker dose? Fndings from the SHIFT (systolic heart failure treatment with the I(f) inhibitor ivabradine trial) Study. J Am Coll Cardiol. 2012;59(22):1938–45.PubMedCrossRef
62.
go back to reference Sarullo FM, Fazio G, Puccio D, Fasullo S, Paterna S, Novo S, Di Pasquale P. Impact of “off-label” use of ivabradine on exercise capacity, gas exchange, functional class, quality of life, and neurohormonal modulation in patients with ischemic chronic heart failure. J Cardiovasc Pharmacol Ther. 2010;15(4):349–55.PubMedCrossRef Sarullo FM, Fazio G, Puccio D, Fasullo S, Paterna S, Novo S, Di Pasquale P. Impact of “off-label” use of ivabradine on exercise capacity, gas exchange, functional class, quality of life, and neurohormonal modulation in patients with ischemic chronic heart failure. J Cardiovasc Pharmacol Ther. 2010;15(4):349–55.PubMedCrossRef
64.
go back to reference De Ferrari GM, Mazzuero A, Agnesina L, Bertoletti A, Lettino M, Campana C, Schwartz PJ, Tavazzi L. Favourable effects of heart rate reduction with intravenous administration of ivabradine in patients with advanced heart failure. Eur J Heart Fail. 2008;10(6):550–5.PubMedCrossRef De Ferrari GM, Mazzuero A, Agnesina L, Bertoletti A, Lettino M, Campana C, Schwartz PJ, Tavazzi L. Favourable effects of heart rate reduction with intravenous administration of ivabradine in patients with advanced heart failure. Eur J Heart Fail. 2008;10(6):550–5.PubMedCrossRef
65.
go back to reference Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251–9.PubMedCrossRef Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251–9.PubMedCrossRef
66.
go back to reference Setaro JF, Zaret BL, Schulman DS, Black HR, Soufer R. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Am J Cardiol. 1990;66:981–6.PubMedCrossRef Setaro JF, Zaret BL, Schulman DS, Black HR, Soufer R. Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance. Am J Cardiol. 1990;66:981–6.PubMedCrossRef
67.
go back to reference Hung MJ, Cherng WJ, Kuo LT, Wang CH. Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure. Int J Clin Pract. 2002;56:57–62.PubMed Hung MJ, Cherng WJ, Kuo LT, Wang CH. Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure. Int J Clin Pract. 2002;56:57–62.PubMed
68.
go back to reference van Veldhuisen DJ, Cohen-Solal A, Böhm M, et al. Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction: data from SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure). J Am Coll Cardiol. 2009;53:2150–8.PubMedCrossRef van Veldhuisen DJ, Cohen-Solal A, Böhm M, et al. Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction: data from SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure). J Am Coll Cardiol. 2009;53:2150–8.PubMedCrossRef
69.
go back to reference Bergstrom A, Andersson B, Edner M, Nylander E, Persson H, Dahlstrom U. Effect of carvedilol on diastolic function in patients with diastolic heart failure and preserved systolic function. Results of the Swedish Doppler-Echocardiographic Study (SWEDIC). Eur J Heart Fail. 2004;6:453–61.PubMedCrossRef Bergstrom A, Andersson B, Edner M, Nylander E, Persson H, Dahlstrom U. Effect of carvedilol on diastolic function in patients with diastolic heart failure and preserved systolic function. Results of the Swedish Doppler-Echocardiographic Study (SWEDIC). Eur J Heart Fail. 2004;6:453–61.PubMedCrossRef
70.
go back to reference Kosmala W, Holland DJ, Rojek A, Wright L, Przewlocka-Kosmala M, Marwick TH. Effect of if-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction: a randomized trial. J Am Coll Cardiol. 2013;62(15):1330–8.PubMedCrossRef Kosmala W, Holland DJ, Rojek A, Wright L, Przewlocka-Kosmala M, Marwick TH. Effect of if-channel inhibition on hemodynamic status and exercise tolerance in heart failure with preserved ejection fraction: a randomized trial. J Am Coll Cardiol. 2013;62(15):1330–8.PubMedCrossRef
71.
go back to reference Reil JC, Hohl M, Reil GH, Granzier HL, Kratz MT, Kazakov A, Fries P, Müller A, Lenski M, Custodis F, Gräber S, Fröhlig G, Steendijk P, Neuberger HR, Böhm M. Heart rate reduction by If-inhibition improves vascular stiffness and left ventricular systolic and diastolic function in a mouse model of heart failure with preserved ejection fraction. Eur Heart J. 2013;34(36):2839–49.PubMedCrossRef Reil JC, Hohl M, Reil GH, Granzier HL, Kratz MT, Kazakov A, Fries P, Müller A, Lenski M, Custodis F, Gräber S, Fröhlig G, Steendijk P, Neuberger HR, Böhm M. Heart rate reduction by If-inhibition improves vascular stiffness and left ventricular systolic and diastolic function in a mouse model of heart failure with preserved ejection fraction. Eur Heart J. 2013;34(36):2839–49.PubMedCrossRef
72.
go back to reference Colin P, Ghaleh B, Hittinger L, et al. Differential effects of heart-rate reduction and b-blockade on left ventricular relaxation during exercise. Am J Physiol Heart Circ Physiol. 2002;282:H672–9.PubMed Colin P, Ghaleh B, Hittinger L, et al. Differential effects of heart-rate reduction and b-blockade on left ventricular relaxation during exercise. Am J Physiol Heart Circ Physiol. 2002;282:H672–9.PubMed
Metadata
Title
Beta-Blockers and Ivabradine in Chronic Heart Failure: From Clinical Trials to Clinical Practice
Authors
Antonino Di Franco
Filippo M. Sarullo
Ylenia Salerno
Stefano Figliozzi
Rossella Parrinello
Pietro Di Pasquale
Gaetano A. Lanza
Publication date
01-04-2014
Publisher
Springer International Publishing
Published in
American Journal of Cardiovascular Drugs / Issue 2/2014
Print ISSN: 1175-3277
Electronic ISSN: 1179-187X
DOI
https://doi.org/10.1007/s40256-013-0057-9

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