Gilbert E M, Abraham W T, Olsen S, Hattler B, White M, Mealy P, Larrabee P, Bristow M R
University of Utah School of Medicine, Salt Lake City, USA.
Circulation. 1996 Dec 1;94(11):2817-25. doi: 10.1161/01.cir.94.11.2817.
The basic pharmacology of the third-generation beta-blocking agent carvedilol differs considerably from second-generation compounds such as metoprolol. Moreover, carvedilol may produce different, ie, more favorable, clinical effects in chronic heart failure. For these reasons, we compared the effects of carvedilol and metoprolol on adrenergic activity, receptor expression, degree of clinical beta-blockade, hemodynamics, and left ventricular function in patients with mild or moderate chronic heart failure.
The effects of carvedilol versus metoprolol were compared in two concurrent placebo-controlled trials with carvedilol or metoprolol that had common substudies focused on adrenergic, hemodynamic, and left ventricular functional measurements. All subjects in the substudies had chronic heart failure resulting from idiopathic dilated cardiomyopathy. Carvedilol at 50 to 100 mg/d produced reductions in exercise heart rate that were similar to metoprolol at 125 to 150 mg/d, indicating comparable degrees of beta-blockade. Compared with metoprolol, carvedilol was associated with greater improvement in New York Heart Association functional class. Although there were no significant differences in hemodynamic effects between the carvedilol and metoprolol active-treatment groups, carvedilol tended to produce relatively greater improvements in left ventricular ejection fraction, stroke volume, and stroke work compared with changes in the respective placebo groups. Carvedilol selectively lowered coronary sinus norepinephrine levels, an index of cardiac adrenergic activity, whereas metoprolol did not lower coronary sinus norepinephrine and actually increased central venous norepinephrine levels. Finally, metoprolol was associated with an increase in cardiac beta-receptor density, whereas carvedilol did not change cardiac beta-receptor expression.
The third-generation beta-blocking agent carvedilol has substantially different effects on left ventricular function, hemodynamics, adrenergic activity, and beta-receptor expression than dose the second-generation compound metoprolol. Some or all of these differences may explain the apparent differences in clinical results between the two compounds.
第三代β受体阻滞剂卡维地洛的基本药理学与第二代化合物如美托洛尔有很大不同。此外，卡维地洛在慢性心力衰竭中可能产生不同的，即更有利的临床效果。基于这些原因，我们比较了卡维地洛和美托洛尔对轻、中度慢性心力衰竭患者肾上腺素能活性、受体表达、临床β受体阻滞程度、血流动力学和左心室功能的影响。
在两项同时进行的安慰剂对照试验中比较了卡维地洛与美托洛尔的效果，这两项试验分别使用卡维地洛或美托洛尔，并有共同的子研究聚焦于肾上腺素能、血流动力学和左心室功能测量。子研究中的所有受试者均患有特发性扩张型心肌病导致的慢性心力衰竭。50至100mg/d的卡维地洛降低运动心率的效果与125至150mg/d的美托洛尔相似，表明β受体阻滞程度相当。与美托洛尔相比，卡维地洛与纽约心脏协会心功能分级的更大改善相关。虽然卡维地洛和美托洛尔活性治疗组之间的血流动力学效应没有显著差异，但与各自安慰剂组的变化相比，卡维地洛在左心室射血分数、每搏输出量和每搏功方面往往产生相对更大的改善。卡维地洛选择性降低冠状窦去甲肾上腺素水平，这是心脏肾上腺素能活性的一个指标，而美托洛尔没有降低冠状窦去甲肾上腺素水平，实际上还增加了中心静脉去甲肾上腺素水平。最后，美托洛尔与心脏β受体密度增加有关，而卡维地洛没有改变心脏β受体表达。
第三代β受体阻滞剂卡维地洛在左心室功能、血流动力学、肾上腺素能活性和β受体表达方面与第二代化合物美托洛尔有显著不同的影响。这些差异中的一些或全部可能解释了这两种化合物在临床结果上的明显差异。
