Carvedilol improves left ventricular function and symptoms in chronic heart failure: a double-blind randomized study
SL Olsen,
EM Gilbert,
DG Renlund,
DO Taylor,
FD Yanowitz,
and
MR Bristow
Division of Cardiology, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
OBJECTIVES. This study assessed the safety and efficacy of carvedilol in patients with heart failure caused by idiopathic or ischemic cardiomyopathy. BACKGROUND. Carvedilol is a mildly beta 1-selective beta-adrenergic blocking agent with vasodilator properties. Beta-blockade may be beneficial in patients with heart failure, but the effects of carvedilol are not known. METHODS. Sixty patients with heart failure (New York Heart Association functional classes II to IV) and left ventricular ejection fraction < or = 0.35 were enrolled in the study. All patients tolerated challenge with carvedilol, 3.125 mg twice a day, and were randomized to receive carvedilol (n = 36) versus placebo (n = 24). Study medication was titrated over 1 month from 6.25 to 25 mg twice a day (< 75 kg) or 50 mg twice a day (> 75 kg) and continued for 3 months. One placebo-treated and two carvedilol-treated patients did not complete the study. RESULTS. Carvedilol therapy resulted in a significant reduction in heart rate and mean pulmonary artery and pulmonary capillary wedge pressures and a significant increase in stroke volume and left ventricular stroke work. Left ventricular ejection fraction increased 52% in the carvedilol group (from 0.21 to 0.32, p < 0.0001 vs. placebo group). Carvedilol-treated patients also reported a significant lessening of heart failure symptoms (p < 0.05 vs. placebo group). Submaximal exercise duration tended to increase with carvedilol therapy (from 688 +/- 31 s to 871 +/- 32 s), but this change was not significantly different from that with placebo therapy by between-group analysis. Peak oxygen consumption during maximal exercise did not change. CONCLUSIONS. Long-term carvedilol therapy improves rest cardiac function and lessens symptoms in patients with heart failure.
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D. Domanski and E. R. Schwarz
Clinical Review: Is the Perioperative Use of {beta}-Blockers Still Recommended? A Critical Review of Recent Controversies
Journal of Cardiovascular Pharmacology and Therapeutics,
December 1, 2009;
14(4):
258 - 268.
[Abstract]
[PDF]
|
|
|
|
|
|
|
F. A. McAlister, N. Wiebe, J. A. Ezekowitz, A. A. Leung, and P. W. Armstrong
Meta-analysis: {beta}-Blocker Dose, Heart Rate Reduction, and Death in Patients With Heart Failure
Ann Intern Med,
June 2, 2009;
150(11):
784 - 794.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al.
2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation
J. Am. Coll. Cardiol.,
April 14, 2009;
53(15):
e1 - e90.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Jessup, W. T. Abraham, D. E. Casey, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. A. Konstam, D. M. Mancini, P. S. Rahko, M. A. Silver, et al.
2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation
J. Am. Coll. Cardiol.,
April 14, 2009;
53(15):
1343 - 1382.
[Full Text]
[PDF]
|
|
|
|
|
|
|
2009 WRITING GROUP TO REVIEW NEW EVIDENCE AND UPDA, M. Jessup, W. T. Abraham, D. E. Casey, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. A. Konstam, D. M. Mancini, P. S. Rahko, et al.
2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation
Circulation,
April 14, 2009;
119(14):
1977 - 2016.
[Full Text]
[PDF]
|
|
|
|
|
|
|
2005 WRITING COMMITTEE MEMBERS, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, et al.
2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation
Circulation,
April 14, 2009;
119(14):
e391 - e479.
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Oldenburg, A. Schmidt, B. Lamp, T. Bitter, B. G. Muntean, C. Langer, and D. Horstkotte
Adaptive servoventilation improves cardiac function in patients with chronic heart failure and Cheyne-Stokes respiration
Eur J Heart Fail,
June 1, 2008;
10(6):
581 - 586.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. F. Murphy, C. O'Loughlin, M. Ledwidge, D. McCaffrey, and K. McDonald
Improvement but no cure of left ventricular systolic dysfunction in treated heart failure patients
Eur J Heart Fail,
December 1, 2007;
9(12):
1196 - 1204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. A. Nasr, A. Bouzamondo, J.-S. Hulot, O. Dubourg, J.-Y. Le Heuzey, and P. Lechat
Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a meta-analysis
Eur. Heart J.,
February 8, 2007;
(2007)
ehl484v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Abdulla, L. Kober, E. Christensen, and C. Torp-Pedersen
Effect of beta-blocker therapy on functional status in patients with heart failure -- A meta-analysis
Eur J Heart Fail,
August 1, 2006;
8(5):
522 - 531.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Funck-Brentano
Beta-blockade in CHF: from contraindication to indication
Eur. Heart J. Suppl.,
June 1, 2006;
8(suppl_C):
C19 - C27.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Cohen-Solal, F. Rouzet, A. Berdeaux, D. Le Guludec, E. Abergel, A. Syrota, and P. Merlet
Effects of Carvedilol on Myocardial Sympathetic Innervation in Patients with Chronic Heart Failure
J. Nucl. Med.,
November 1, 2005;
46(11):
1796 - 1803.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Developed in Collaboration With the American Colle, Endorsed by the Heart Rhythm Society, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, et al.
ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure)
J. Am. Coll. Cardiol.,
September 20, 2005;
46(6):
1116 - 1143.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al.
ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society
Circulation,
September 20, 2005;
112(12):
1825 - 1852.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. R. Schwarz, R. Gupta, T. P. Diep, B. Nowak, S. Kostin, B. Grohmann, B. F. Uretsky, and J. Schaper
Carvedilol Improves Myocardial Contractility Compared With Metoprolol in Patients With Chronic Hibernating Myocardium After Revascularization
Journal of Cardiovascular Pharmacology and Therapeutics,
July 1, 2005;
10(3):
181 - 190.
[Abstract]
[PDF]
|
|
|
|
|
|
|
B. F. McBride and C. M. White
Critical Differences Among Beta-Adrenoreceptor Antagonists in Myocardial Failure: Debating the MERIT of COMET
J. Clin. Pharmacol.,
January 1, 2005;
45(1):
6 - 24.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kawai, F. Qin, J. Shite, W. Mao, S. Fukuoka, and C.-s. Liang
Importance of antioxidant and antiapoptotic effects of {beta}-receptor blockers in heart failure therapy
Am J Physiol Heart Circ Physiol,
September 1, 2004;
287(3):
H1003 - H1012.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. E. Sirak, S. Jelic, and T. H. Le Jemtel
Therapeutic update: Non-selective beta- and alpha-adrenergic blockade in patients with coexistent chronic obstructive pulmonary disease and chronic heart failure
J. Am. Coll. Cardiol.,
August 4, 2004;
44(3):
497 - 502.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Penicka, J. Bartunek, B. De Bruyne, M. Vanderheyden, M. Goethals, M. De Zutter, P. Brugada, and P. Geelen
Improvement of Left Ventricular Function After Cardiac Resynchronization Therapy Is Predicted by Tissue Doppler Imaging Echocardiography
Circulation,
March 2, 2004;
109(8):
978 - 983.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. de Groote, N. Helbecque, N. Lamblin, X. Hermant, P. Amouyel, C. Bauters, and J. Dallongeville
Beta-adrenergic receptor blockade and the angiotensin-converting enzyme deletion polymorphism in patients with chronic heart failure
Eur J Heart Fail,
January 1, 2004;
6(1):
17 - 21.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. G. Shlipak
Pharmacotherapy for Heart Failure in Patients with Renal Insufficiency
Ann Intern Med,
June 3, 2003;
138(11):
917 - 924.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. H. Barry and E. M. Gilbert
How Do {beta}-Blockers Improve Ventricular Function in Patients With Congestive Heart Failure?
Circulation,
May 20, 2003;
107(19):
2395 - 2397.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Palazzuoli, F. Bruni, L. Puccetti, M. Pastorelli, P. Angori, A.L. Pasqui, and A. Auteri
Effects of carvedilol on left ventricular remodeling and systolic function in elderly patients with heart failure
Eur J Heart Fail,
December 1, 2002;
4(6):
765 - 770.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kubo, E. R. Azevedo, G. E. Newton, J. D. Parker, and J. S. Floras
Lack of evidence for peripheral alpha1- adrenoceptor blockade during long-term treatment of heart failure with carvedilol
J. Am. Coll. Cardiol.,
November 1, 2001;
38(5):
1463 - 1469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.K. Agarwal and P. Venugopalan
Beneficial effect of carvedilol on heart rate response to exercise in digitalised patients with heart failure in atrial fibrillation due to idiopathic dilated cardiomyopathy
Eur J Heart Fail,
August 1, 2001;
3(4):
437 - 440.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Gullestad, C. Manhenke, T. Aarsland, R. Skardal, H. Fagertun, J. Wikstrand, and J. Kjekshus
Effect of metoprolol CR/XL on exercise tolerance in chronic heart failure -- a substudy to the MERIT-HF trial
Eur J Heart Fail,
August 1, 2001;
3(4):
463 - 468.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.F. Forissier, P. Vernochet, P. Bertrand, B. Charbonnier, and C. Monpere
Influence of carvedilol on the benefits of physical training in patients with moderate chronic heart failure
Eur J Heart Fail,
June 1, 2001;
3(3):
335 - 342.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Shibata, M. D. Flather, and D. Wang
Systematic review of the impact of beta blockers on mortality and hospital admissions in heart failure
Eur J Heart Fail,
June 1, 2001;
3(3):
351 - 357.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Brophy, L. Joseph, and J. L. Rouleau
{beta}-Blockers in Congestive Heart Failure: A Bayesian Meta-Analysis
Ann Intern Med,
April 3, 2001;
134(7):
550 - 560.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C Opasich, G.D Pinna, A Mazza, O Febo, R Riccardi, P.G Riccardi, S Capomolla, G Forni, F Cobelli, and L Tavazzi
Six-minute walking performance in patients with moderate-to-severe heart failure; is it a useful indicator in clinical practice?
Eur. Heart J.,
March 2, 2001;
22(6):
488 - 496.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. M. Ramahi, M. D. Longo, A. R. Cadariu, K. Rohlfs, S. A. Carolan, K. M. Engle, H. Samady, and F. J. T. Wackers
Left ventricular inotropic reserve and right ventricular function predict increase of left ventricular ejection fraction after beta-blocker therapy in nonischemic cardiomyopathy
J. Am. Coll. Cardiol.,
March 1, 2001;
37(3):
818 - 824.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Dargie and The CAPRICORN Steering Committee
Design and methodology of the CAPRICORN trial -- a randomised double blind placebo controlled study of the impact of carvedilol on morbidity and mortality in patients with left ventricular dysfunction after myocardial infarction
Eur J Heart Fail,
September 1, 2000;
2(3):
325 - 332.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Kukin, M. M. Mannino, R. S. Freudenberger, J. Kalman, C. Buchholz-Varley, and O. Ocampo
Hemodynamic comparison of twice daily metoprolol tartrate with once daily metoprolol succinate in congestive heart failure
J. Am. Coll. Cardiol.,
January 1, 2000;
35(1):
45 - 50.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Di Lenarda, G. Sabbadini, L. Salvatore, G. Sinagra, L. Mestroni, B. Pinamonti, D. Gregori, F. Ciani, A. Muzzi, S. Klugmann, et al.
Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol
J. Am. Coll. Cardiol.,
June 1, 1999;
33(7):
1926 - 1934.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Macdonald, A. M. Keogh, C. L. Aboyoun, M. Lund, R. Amor, and D. J. McCaffrey
Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure
J. Am. Coll. Cardiol.,
March 15, 1999;
33(4):
924 - 931.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Carlson and K. Oberg
Clinical Pharmacology of Carvedilol
Journal of Cardiovascular Pharmacology and Therapeutics,
January 1, 1999;
4(4):
205 - 218.
[Abstract]
[PDF]
|
|
|
|
|
|
|
W. T. Abraham
Pharmacologic Management of Chronic Heart Failure: A Review
Seminars in Cardiothoracic and Vascular Anesthesia,
September 1, 1998;
2(3):
168 - 190.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. D. Sackner-Bernstein and D. M. Mancini
Rationale for Treatment of Patients With Chronic Heart Failure With Adrenergic Blockade
JAMA,
November 8, 1995;
274(18):
1462 - 1467.
[Abstract]
[PDF]
|
|
|
|
