Prognostic role of β-blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database

S. Paolillo, M. Mapelli, A. Bonomi, U. Corrà, M. Piepoli, F. Veglia, E. Salvioni, P. Gentile, R. Lagioia, M. Metra, G. Limongelli, G. Sinagra, G. Cattadori, A.B. Scardovi, V. Carubelli, D. Scrutino, R. Badagliacca, R. Raimondo, M. Emdin, D. MagrìM. Correale, G. Parati, S. Caravita, E. Spadafora, F. Re, M. Cicoira, M. Frigerio, M. Bussotti, C. Minà, F. Oliva, E. Battaia, R. Belardinelli, A. Mezzani, L. Pastormerlo, A. Di Lenarda, C. Passino, S. Sciomer, A. Iorio, E. Zambon, M. Guazzi, G. Pacileo, R. Ricci, M. Contini, A. Apostolo, P. Palermo, F. Clemenza, G. Marchese, C. Lombardi, A. Passantino, P. Agostoni

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Aims: The use of β-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared β-blockers in HFrEF, and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients (MECKI score database) the association of β-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of β-selectivity and dosage regimens. Methods and results: In 5242 HFrEF patients, we investigated the role of: (i) β-blocker treatment vs. non-β-blocker treatment, (ii) β1-/β2-receptor-blockers vs. β1-selective blockers, and (iii) daily β-blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on β-blockers, while 807 (13.2%) were not. At 5 years, β-blocker-patients showed a better outcome than non-β-blocker-subjects [hazard ratio (HR) 0.48, P <0.0001], while also considering potential confounders. A comparable prognosis was observed at 5 years in the β1-/β2-receptor-blocker (n = 2219) vs. β1-selective group (n = 2216) (HR 0.95, P = ns). A better prognosis was observed in high-dose (>2 5 mg carvedilol equivalent daily dose, n = 1005) patients than in both medium dose (12.5–25 mg, n = 1431) and low dose (
Original languageEnglish
Pages (from-to)904-914
Number of pages11
JournalEuropean Journal of Heart Failure
Volume19
Issue number7
DOIs
Publication statusPublished - 2017

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Heart Failure
Databases
Heart-Assist Devices
Heart Transplantation
Treatment Failure
Therapeutics

Keywords

  • Equivalent dose
  • Heart failure
  • Prognosis
  • β-Blocker selectivity
  • β-Blockers
  • beta adrenergic receptor blocking agent
  • bisoprolol
  • carvedilol
  • metoprolol
  • nebivolol
  • adult
  • Article
  • cohort analysis
  • controlled study
  • drug dose regimen
  • drug megadose
  • drug selectivity
  • female
  • heart failure with reduced ejection fraction
  • human
  • low drug dose
  • major clinical study
  • male
  • Metabolic Exercise Cardiac Kidney Index score
  • priority journal
  • prognosis
  • retrospective study
  • scoring system
  • treatment outcome

Cite this

Prognostic role of β-blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database. / Paolillo, S.; Mapelli, M.; Bonomi, A.; Corrà, U.; Piepoli, M.; Veglia, F.; Salvioni, E.; Gentile, P.; Lagioia, R.; Metra, M.; Limongelli, G.; Sinagra, G.; Cattadori, G.; Scardovi, A.B.; Carubelli, V.; Scrutino, D.; Badagliacca, R.; Raimondo, R.; Emdin, M.; Magrì, D.; Correale, M.; Parati, G.; Caravita, S.; Spadafora, E.; Re, F.; Cicoira, M.; Frigerio, M.; Bussotti, M.; Minà, C.; Oliva, F.; Battaia, E.; Belardinelli, R.; Mezzani, A.; Pastormerlo, L.; Di Lenarda, A.; Passino, C.; Sciomer, S.; Iorio, A.; Zambon, E.; Guazzi, M.; Pacileo, G.; Ricci, R.; Contini, M.; Apostolo, A.; Palermo, P.; Clemenza, F.; Marchese, G.; Lombardi, C.; Passantino, A.; Agostoni, P.

In: European Journal of Heart Failure, Vol. 19, No. 7, 2017, p. 904-914.

Research output: Contribution to journalArticle

Paolillo, S, Mapelli, M, Bonomi, A, Corrà, U, Piepoli, M, Veglia, F, Salvioni, E, Gentile, P, Lagioia, R, Metra, M, Limongelli, G, Sinagra, G, Cattadori, G, Scardovi, AB, Carubelli, V, Scrutino, D, Badagliacca, R, Raimondo, R, Emdin, M, Magrì, D, Correale, M, Parati, G, Caravita, S, Spadafora, E, Re, F, Cicoira, M, Frigerio, M, Bussotti, M, Minà, C, Oliva, F, Battaia, E, Belardinelli, R, Mezzani, A, Pastormerlo, L, Di Lenarda, A, Passino, C, Sciomer, S, Iorio, A, Zambon, E, Guazzi, M, Pacileo, G, Ricci, R, Contini, M, Apostolo, A, Palermo, P, Clemenza, F, Marchese, G, Lombardi, C, Passantino, A & Agostoni, P 2017, 'Prognostic role of β-blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database', European Journal of Heart Failure, vol. 19, no. 7, pp. 904-914. https://doi.org/10.1002/ejhf.775
Paolillo, S. ; Mapelli, M. ; Bonomi, A. ; Corrà, U. ; Piepoli, M. ; Veglia, F. ; Salvioni, E. ; Gentile, P. ; Lagioia, R. ; Metra, M. ; Limongelli, G. ; Sinagra, G. ; Cattadori, G. ; Scardovi, A.B. ; Carubelli, V. ; Scrutino, D. ; Badagliacca, R. ; Raimondo, R. ; Emdin, M. ; Magrì, D. ; Correale, M. ; Parati, G. ; Caravita, S. ; Spadafora, E. ; Re, F. ; Cicoira, M. ; Frigerio, M. ; Bussotti, M. ; Minà, C. ; Oliva, F. ; Battaia, E. ; Belardinelli, R. ; Mezzani, A. ; Pastormerlo, L. ; Di Lenarda, A. ; Passino, C. ; Sciomer, S. ; Iorio, A. ; Zambon, E. ; Guazzi, M. ; Pacileo, G. ; Ricci, R. ; Contini, M. ; Apostolo, A. ; Palermo, P. ; Clemenza, F. ; Marchese, G. ; Lombardi, C. ; Passantino, A. ; Agostoni, P. / Prognostic role of β-blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database. In: European Journal of Heart Failure. 2017 ; Vol. 19, No. 7. pp. 904-914.
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title = "Prognostic role of β-blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database",
abstract = "Aims: The use of β-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared β-blockers in HFrEF, and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients (MECKI score database) the association of β-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of β-selectivity and dosage regimens. Methods and results: In 5242 HFrEF patients, we investigated the role of: (i) β-blocker treatment vs. non-β-blocker treatment, (ii) β1-/β2-receptor-blockers vs. β1-selective blockers, and (iii) daily β-blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3{\%}) were observed; 4435 patients (86.8{\%}) were on β-blockers, while 807 (13.2{\%}) were not. At 5 years, β-blocker-patients showed a better outcome than non-β-blocker-subjects [hazard ratio (HR) 0.48, P <0.0001], while also considering potential confounders. A comparable prognosis was observed at 5 years in the β1-/β2-receptor-blocker (n = 2219) vs. β1-selective group (n = 2216) (HR 0.95, P = ns). A better prognosis was observed in high-dose (>2 5 mg carvedilol equivalent daily dose, n = 1005) patients than in both medium dose (12.5–25 mg, n = 1431) and low dose (",
keywords = "Equivalent dose, Heart failure, Prognosis, β-Blocker selectivity, β-Blockers, beta adrenergic receptor blocking agent, bisoprolol, carvedilol, metoprolol, nebivolol, adult, Article, cohort analysis, controlled study, drug dose regimen, drug megadose, drug selectivity, female, heart failure with reduced ejection fraction, human, low drug dose, major clinical study, male, Metabolic Exercise Cardiac Kidney Index score, priority journal, prognosis, retrospective study, scoring system, treatment outcome",
author = "S. Paolillo and M. Mapelli and A. Bonomi and U. Corr{\`a} and M. Piepoli and F. Veglia and E. Salvioni and P. Gentile and R. Lagioia and M. Metra and G. Limongelli and G. Sinagra and G. Cattadori and A.B. Scardovi and V. Carubelli and D. Scrutino and R. Badagliacca and R. Raimondo and M. Emdin and D. Magr{\`i} and M. Correale and G. Parati and S. Caravita and E. Spadafora and F. Re and M. Cicoira and M. Frigerio and M. Bussotti and C. Min{\`a} and F. Oliva and E. Battaia and R. Belardinelli and A. Mezzani and L. Pastormerlo and {Di Lenarda}, A. and C. Passino and S. Sciomer and A. Iorio and E. Zambon and M. Guazzi and G. Pacileo and R. Ricci and M. Contini and A. Apostolo and P. Palermo and F. Clemenza and G. Marchese and C. Lombardi and A. Passantino and P. Agostoni",
note = "Cited By :3 Export Date: 6 March 2018 CODEN: EJHFF Correspondence Address: Agostoni, P.; Centro Cardiologico Monzino, IRCCSItaly; email: piergiuseppe.agostoni@unimi.it Chemicals/CAS: bisoprolol, 66722-44-9; carvedilol, 72956-09-3; metoprolol, 37350-58-6; nebivolol, 99200-09-6, 118457-15-1, 118457-16-2 References: Ponikowski, P., Voors, A.A., Anker, S.D., Bueno, H., Cleland, J.G., Coats, A.J., Falk, V., van der Meer, P., 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC (2016) Eur J Heart Fail, 18, pp. 891-975; Yancy, C.W., Jessup, M., Bozkurt, B., Butler, J., Casey, D.E., Jr., Colvin, M.M., Drazner, M.H., Westlake, C., 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: an update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America (2016) J Am Coll Cardiol, 68, pp. 1476-1488; Lechat, P., Packer, M., Chalon, S., Cucherat, M., Arab, T., Boissel, J.P., Clinical effects of beta-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials (1998) Circulation, 98, pp. 1184-1191; Paolillo, S., Pellegrino, R., Salvioni, E., Contini, M., Iorio, A., Bovis, F., Antonelli, A., Agostoni, P., Role of alveolar beta2-adrenergic receptors on lung fluid clearance and exercise ventilation in healthy humans (2013) PLoS One, 8; Contini, M., Apostolo, A., Cattadori, G., Paolillo, S., Iorio, A., Bertella, E., Salvioni, E., Agostoni, P., Multiparametric comparison of CARvedilol, vs. NEbivolol, vs. BIsoprolol in moderate heart failure: the CARNEBI trial (2013) Int J Cardiol, 168, pp. 2134-2140; Agostoni, P., Contini, M., Cattadori, G., Apostolo, A., Sciomer, S., Bussotti, M., Palermo, P., Fiorentini, C., Lung function with carvedilol and bisoprolol in chronic heart failure: is beta selectivity relevant? (2007) Eur J Heart Fail, 9, pp. 827-833; Packer, M., Bristow, M.R., Cohn, J.N., Colucci, W.S., Fowler, M.B., Gilbert, E.M., Shusterman, N.H., The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group (1996) N Engl J Med, 334, pp. 1349-1355; Packer, M., Fowler, M.B., Roecker, E.B., Coats, A.J., Katus, H.A., Krum, H., Mohacsi, P., DeMets, D.L., Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study (2002) Circulation, 106, pp. 2194-2199; The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial (1999) Lancet, 353, pp. 9-13; Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) (1999) Lancet, 353, pp. 2001-2007; Flather, M.D., Shibata, M.C., Coats, A.J., Van Veldhuisen, D.J., Parkhomenko, A., Borbola, J., Cohen-Solal, A., Poole-Wilson, P.A., Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS) (2005) Eur Heart J, 26, pp. 215-225; Poole-Wilson, P.A., Swedberg, K., Cleland, J.G., Di Lenarda, A., Hanrath, P., Komajda, M., Lubsen, J., Skene, A., Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial (2003) Lancet, 362, pp. 7-13; Bristow, M.R., Feldman, A.M., Adams, K.F., Jr., Goldstein, S., Selective versus nonselective beta-blockade for heart failure therapy: are there lessons to be learned from the COMET trial? (2003) J Card Fail, 9, pp. 444-453; Packer, M., Do beta-blockers prolong survival in heart failure only by inhibiting the beta1-receptor? A perspective on the results of the COMET trial (2003) J Card Fail, 9, pp. 429-443; Bolling, R., Scheller, N.M., Kober, L., Poulsen, H.E., Gislason, G.H., Torp-Pedersen, C., Comparison of the clinical outcome of different beta-blockers in heart failure patients: a retrospective nationwide cohort study (2014) Eur J Heart Fail, 16, pp. 678-684; Pasternak, B., Svanstrom, H., Melbye, M., Hviid, A., Association of treatment with carvedilol vs metoprolol succinate and mortality in patients with heart failure (2014) JAMA Intern Med, 174, pp. 1597-1604; Chatterjee, S., Biondi-Zoccai, G., Abbate, A., D'Ascenzo, F., Castagno, D., Van Tassell, B., Mukherjee, D., Lichstein, E., Benefits of beta blockers in patients with heart failure and reduced ejection fraction: network meta-analysis (2013) BMJ, 346, p. f55; Mrdovic, I.B., Savic, L.Z., Perunicic, J.P., Asanin, M.R., Lasica, R.M., Jelena, M.M., Matic, M.D., Ostojic, M.C., Randomized active-controlled study comparing effects of treatment with carvedilol versus metoprolol in patients with left ventricular dysfunction after acute myocardial infarction (2007) Am Heart J, 154, pp. 116-122; Fiuzat, M., Wojdyla, D., Kitzman, D., Fleg, J., Keteyian, S.J., Kraus, W.E., Pina, I.L., O'Connor, C.M., 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 (2012) J Am Coll Cardiol, 60, pp. 208-215; Bristow, M.R., Gilbert, E.M., Abraham, W.T., Adams, K.F., Fowler, M.B., Hershberger, R.E., Kubo, S.H., Shusterman, N., Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators (1996) Circulation, 94, pp. 2807-2816; Agostoni, P., Corra, U., Cattadori, G., Veglia, F., La Gioia, R., Scardovi, A.B., Emdin, M., Passino, C., Metabolic exercise test data combined with cardiac and kidney indexes, the MECKI score: a multiparametric approach to heart failure prognosis (2013) Int J Cardiol, 167, pp. 2710-2718; Piepoli, M.F., Corra, U., Agostoni, P.G., Belardinelli, R., Cohen-Solal, A., Hambrecht, R., Vanhees, L., Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation Part II: how to perform cardiopulmonary exercise testing in chronic heart failure (2006) Eur J Cardiovasc Prev Rehabil, 13, pp. 300-311; Swedberg, K., Cleland, J., Dargie, H., Drexler, H., Follath, F., Komajda, M., Tavazzi, L., Remme, W.J., Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): the Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology (2005) Eur Heart J, 26, pp. 1115-1140; Swedberg, K., Komajda, M., Bohm, M., Borer, J.S., Ford, I., Dubost-Brama, A., Lerebours, G., Tavazzi, L., Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study (2010) Lancet, 376, pp. 875-885; 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?: findings from the SHIFT (Systolic Heart failure treatment with the I(f) inhibitor ivabradine Trial) study (2012) J Am Coll Cardiol, 59, pp. 1938-1945; Waagstein, F., Bristow, M.R., Swedberg, K., Camerini, F., Fowler, M.B., Silver, M.A., Gilbert, E.M., Hjalmarson, A., Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group (1993) Lancet, 342, pp. 1441-1446; DiNicolantonio, J.J., Lavie, C.J., Fares, H., Menezes, A.R., O'Keefe, J.H., Meta-analysis of carvedilol versus beta 1 selective beta-blockers (atenolol, bisoprolol, metoprolol, and nebivolol) (2013) Am J Cardiol, 111, pp. 765-769; Bristow, M.R., Treatment of chronic heart failure with beta-adrenergic receptor antagonists: a convergence of receptor pharmacology and clinical cardiology (2011) Circ Res, 109, pp. 1176-1194; Maggioni, A.P., Dahlstrom, U., Filippatos, G., Chioncel, O., Leiro, M.C., Drozdz, J., Fruhwald, F., Tavazzi, L., EURObservational Research Programme: the Heart Failure Pilot Survey (ESC-HF Pilot) (2010) Eur J Heart Fail, 12, pp. 1076-1084; Maggioni, A.P., Anker, S.D., Dahlstrom, U., Filippatos, G., Ponikowski, P., Zannad, F., Amir, O., Tavazzi, L., Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12 440 patients of the ESC Heart Failure Long-Term Registry (2013) Eur J Heart Fail, 15, pp. 1173-1184; McAlister, F.A., Wiebe, N., Ezekowitz, J.A., Leung, A.A., Armstrong, P.W., Meta-analysis: beta-blocker dose, heart rate reduction, and death in patients with heart failure (2009) Ann Intern Med, 150, pp. 784-794",
year = "2017",
doi = "10.1002/ejhf.775",
language = "English",
volume = "19",
pages = "904--914",
journal = "European Journal of Heart Failure",
issn = "1388-9842",
publisher = "John Wiley & Sons, Ltd",
number = "7",

}

TY - JOUR

T1 - Prognostic role of β-blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database

AU - Paolillo, S.

AU - Mapelli, M.

AU - Bonomi, A.

AU - Corrà, U.

AU - Piepoli, M.

AU - Veglia, F.

AU - Salvioni, E.

AU - Gentile, P.

AU - Lagioia, R.

AU - Metra, M.

AU - Limongelli, G.

AU - Sinagra, G.

AU - Cattadori, G.

AU - Scardovi, A.B.

AU - Carubelli, V.

AU - Scrutino, D.

AU - Badagliacca, R.

AU - Raimondo, R.

AU - Emdin, M.

AU - Magrì, D.

AU - Correale, M.

AU - Parati, G.

AU - Caravita, S.

AU - Spadafora, E.

AU - Re, F.

AU - Cicoira, M.

AU - Frigerio, M.

AU - Bussotti, M.

AU - Minà, C.

AU - Oliva, F.

AU - Battaia, E.

AU - Belardinelli, R.

AU - Mezzani, A.

AU - Pastormerlo, L.

AU - Di Lenarda, A.

AU - Passino, C.

AU - Sciomer, S.

AU - Iorio, A.

AU - Zambon, E.

AU - Guazzi, M.

AU - Pacileo, G.

AU - Ricci, R.

AU - Contini, M.

AU - Apostolo, A.

AU - Palermo, P.

AU - Clemenza, F.

AU - Marchese, G.

AU - Lombardi, C.

AU - Passantino, A.

AU - Agostoni, P.

N1 - Cited By :3 Export Date: 6 March 2018 CODEN: EJHFF Correspondence Address: Agostoni, P.; Centro Cardiologico Monzino, IRCCSItaly; email: piergiuseppe.agostoni@unimi.it Chemicals/CAS: bisoprolol, 66722-44-9; carvedilol, 72956-09-3; metoprolol, 37350-58-6; nebivolol, 99200-09-6, 118457-15-1, 118457-16-2 References: Ponikowski, P., Voors, A.A., Anker, S.D., Bueno, H., Cleland, J.G., Coats, A.J., Falk, V., van der Meer, P., 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC (2016) Eur J Heart Fail, 18, pp. 891-975; Yancy, C.W., Jessup, M., Bozkurt, B., Butler, J., Casey, D.E., Jr., Colvin, M.M., Drazner, M.H., Westlake, C., 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: an update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America (2016) J Am Coll Cardiol, 68, pp. 1476-1488; Lechat, P., Packer, M., Chalon, S., Cucherat, M., Arab, T., Boissel, J.P., Clinical effects of beta-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials (1998) Circulation, 98, pp. 1184-1191; Paolillo, S., Pellegrino, R., Salvioni, E., Contini, M., Iorio, A., Bovis, F., Antonelli, A., Agostoni, P., Role of alveolar beta2-adrenergic receptors on lung fluid clearance and exercise ventilation in healthy humans (2013) PLoS One, 8; Contini, M., Apostolo, A., Cattadori, G., Paolillo, S., Iorio, A., Bertella, E., Salvioni, E., Agostoni, P., Multiparametric comparison of CARvedilol, vs. NEbivolol, vs. BIsoprolol in moderate heart failure: the CARNEBI trial (2013) Int J Cardiol, 168, pp. 2134-2140; Agostoni, P., Contini, M., Cattadori, G., Apostolo, A., Sciomer, S., Bussotti, M., Palermo, P., Fiorentini, C., Lung function with carvedilol and bisoprolol in chronic heart failure: is beta selectivity relevant? (2007) Eur J Heart Fail, 9, pp. 827-833; Packer, M., Bristow, M.R., Cohn, J.N., Colucci, W.S., Fowler, M.B., Gilbert, E.M., Shusterman, N.H., The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group (1996) N Engl J Med, 334, pp. 1349-1355; Packer, M., Fowler, M.B., Roecker, E.B., Coats, A.J., Katus, H.A., Krum, H., Mohacsi, P., DeMets, D.L., Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study (2002) Circulation, 106, pp. 2194-2199; The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial (1999) Lancet, 353, pp. 9-13; Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) (1999) Lancet, 353, pp. 2001-2007; Flather, M.D., Shibata, M.C., Coats, A.J., Van Veldhuisen, D.J., Parkhomenko, A., Borbola, J., Cohen-Solal, A., Poole-Wilson, P.A., Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS) (2005) Eur Heart J, 26, pp. 215-225; Poole-Wilson, P.A., Swedberg, K., Cleland, J.G., Di Lenarda, A., Hanrath, P., Komajda, M., Lubsen, J., Skene, A., Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial (2003) Lancet, 362, pp. 7-13; Bristow, M.R., Feldman, A.M., Adams, K.F., Jr., Goldstein, S., Selective versus nonselective beta-blockade for heart failure therapy: are there lessons to be learned from the COMET trial? (2003) J Card Fail, 9, pp. 444-453; Packer, M., Do beta-blockers prolong survival in heart failure only by inhibiting the beta1-receptor? 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PY - 2017

Y1 - 2017

N2 - Aims: The use of β-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared β-blockers in HFrEF, and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients (MECKI score database) the association of β-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of β-selectivity and dosage regimens. Methods and results: In 5242 HFrEF patients, we investigated the role of: (i) β-blocker treatment vs. non-β-blocker treatment, (ii) β1-/β2-receptor-blockers vs. β1-selective blockers, and (iii) daily β-blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on β-blockers, while 807 (13.2%) were not. At 5 years, β-blocker-patients showed a better outcome than non-β-blocker-subjects [hazard ratio (HR) 0.48, P <0.0001], while also considering potential confounders. A comparable prognosis was observed at 5 years in the β1-/β2-receptor-blocker (n = 2219) vs. β1-selective group (n = 2216) (HR 0.95, P = ns). A better prognosis was observed in high-dose (>2 5 mg carvedilol equivalent daily dose, n = 1005) patients than in both medium dose (12.5–25 mg, n = 1431) and low dose (

AB - Aims: The use of β-blockers represents a milestone in the treatment of heart failure with reduced ejection fraction (HFrEF). Few studies have compared β-blockers in HFrEF, and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients (MECKI score database) the association of β-blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of β-selectivity and dosage regimens. Methods and results: In 5242 HFrEF patients, we investigated the role of: (i) β-blocker treatment vs. non-β-blocker treatment, (ii) β1-/β2-receptor-blockers vs. β1-selective blockers, and (iii) daily β-blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on β-blockers, while 807 (13.2%) were not. At 5 years, β-blocker-patients showed a better outcome than non-β-blocker-subjects [hazard ratio (HR) 0.48, P <0.0001], while also considering potential confounders. A comparable prognosis was observed at 5 years in the β1-/β2-receptor-blocker (n = 2219) vs. β1-selective group (n = 2216) (HR 0.95, P = ns). A better prognosis was observed in high-dose (>2 5 mg carvedilol equivalent daily dose, n = 1005) patients than in both medium dose (12.5–25 mg, n = 1431) and low dose (

KW - Equivalent dose

KW - Heart failure

KW - Prognosis

KW - β-Blocker selectivity

KW - β-Blockers

KW - beta adrenergic receptor blocking agent

KW - bisoprolol

KW - carvedilol

KW - metoprolol

KW - nebivolol

KW - adult

KW - Article

KW - cohort analysis

KW - controlled study

KW - drug dose regimen

KW - drug megadose

KW - drug selectivity

KW - female

KW - heart failure with reduced ejection fraction

KW - human

KW - low drug dose

KW - major clinical study

KW - male

KW - Metabolic Exercise Cardiac Kidney Index score

KW - priority journal

KW - prognosis

KW - retrospective study

KW - scoring system

KW - treatment outcome

U2 - 10.1002/ejhf.775

DO - 10.1002/ejhf.775

M3 - Article

VL - 19

SP - 904

EP - 914

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

SN - 1388-9842

IS - 7

ER -