Carvedilol - A review of its use in chronic heart failure

被引:56
作者
Keating, GM [1 ]
Jarvis, B [1 ]
机构
[1] Adis Int Ltd, Auckland, New Zealand
关键词
Carvedilol; heart failure; pharmacodynamics; pharmacokinetics; therapeutic use;
D O I
10.2165/00003495-200363160-00006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Carvedilol (Dilatrend(R)) blocks beta(1)-, beta(2)- and alpha(1)-adrenoceptors, and has antioxidant and antiproliferative effects. Carvedilol improved left ventricular ejection fraction (LVEF) in patients with chronic heart failure (CHF) in numerous studies. Moreover, significantly greater increases from baseline in LVEF were seen with carvedilol than with metoprolol in a double-blind, randomised study and in a meta-analysis. Carvedilol also reversed or attenuated left ventricular remodelling in patients with CHF and in those with left ventricular dysfunction after acute myocardial infarction (MI). Combined analysis of studies in the US Carvedilol Heart Failure Trials Program (patients had varying severities of CHF; n = 1094) revealed that mortality was significantly lower in carvedilol than in placebo recipients. In addition, the risk of hospitalisation for any cardiovascular cause was significantly lower with carvedilol than with placebo. Mortality was significantly lower with carvedilol than with metoprolol in patients with mild to severe CHF in the Carvedilol Or Metoprolol European Trial (COMET) [n = 3029]. The Carvedilol Prospective Randomised Cumulative Survival (COPERNICUS) trial (n = 2289) demonstrated that compared with placebo, carvedilol was associated with significant reductions in all-cause mortality and the combined endpoint of death or hospitalisation for any reason in severe CHF. All-cause mortality was reduced in patients who received carvedilol in addition to conventional therapy compared with those who received placebo plus conventional therapy in the Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN) trial (enrolling 1959 patients with left ventricular dysfunction following acute MI). Carvedilol was generally well tolerated in patients with CHF. Adverse events associated with the alpha- and beta-blocking effects of the drug occurred more commonly with carvedilol than with placebo, whereas placebo recipients were more likely to experience worsening heart failure. In conclusion, carvedilol blocks beta(1)-, beta(2)- and alpha(1)-adrenoceptors and has a unique pharmacological profile. It is thought that additional properties of carvedilol (e.g. antioxidant and antiproliferative effects) contribute to its beneficial effects in CHF. Carvedilol improves ventricular function and reduces mortality and morbidity in patients with mild to severe CHF, and should be considered a standard treatment option in this setting. Administering carvedilol in addition to conventional therapy reduces mortality and attenuates myocardial remodelling in patients with left ventricular dysfunction following acute MI. Moreover, mortality was significantly lower with carvedilol than with metoprolol in patients with mild to severe CHF, suggesting that carvedilol may be the preferred beta-blocker.
引用
收藏
页码:1697 / 1741
页数:45
相关论文
共 177 条
  • [1] Abraham WT, 1998, CIRCULATION, V98, P378
  • [2] Carvedilol reduces the inappropriate increase of ventilation during exercise in heart failure patients
    Agostoni, P
    Guazzi, M
    Bussotti, M
    De Vita, S
    Palermo, P
    [J]. CHEST, 2002, 122 (06) : 2062 - 2067
  • [3] Al-Hesayen A, 2000, CIRCULATION, V102, P779
  • [4] Bucindolol displays intrinsic sympathomimetic activity in human myocardium
    Andreka, P
    Aiyar, N
    Olson, LC
    Wei, JQ
    Turner, MS
    Webster, KA
    Ohlstein, EH
    Bishopric, NH
    [J]. CIRCULATION, 2002, 105 (20) : 2429 - 2434
  • [5] Angermann C. E., 2001, Journal of Heart and Lung Transplantation, V20, P250, DOI 10.1016/S1053-2498(00)00570-2
  • [6] Anker SD, 2002, EUR HEART J, V23, P394
  • [7] Antioxidant properties of carvedilol and metoprolol in heart failure: A double-blind randomized controlled trial
    Arumanayagam, M
    Chan, S
    Tong, S
    Sanderson, JE
    [J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2001, 37 (01) : 48 - 54
  • [8] No effect of carvedilol on nitric oxide generation in phagocytes but modulation of production of superoxide ions
    Åsbrink, S
    Zickert, A
    Bratt, J
    Gyllenhammar, H
    Palmblad, J
    [J]. BIOCHEMICAL PHARMACOLOGY, 2000, 59 (08) : 1007 - 1013
  • [9] Basu S, 1997, CIRCULATION, V96, P183
  • [10] Berdeaux A, 2000, CIRCULATION, V102, P627