[New and old beta-blockers in the treatment of heart failure].
[New and old beta-blockers in the treatment of heart failure].
复制标题
新旧β受体阻滞剂在心力衰竭治疗中的作用[J].
作者：
M. Metra;S. Nodari;T. Bignotti;P. Gnesin;E. Trussardi;L. Cas
迄今为止，在16，000多名患者中进行的对照临床试验一直显示长期β受体阻滞剂治疗对慢性心力衰竭患者的有益作用。然而，尚不清楚这是否代表一种类别效应，或者仅对某些制剂具有特异性。美托洛尔、比索洛尔和卡维地洛对轻中度心力衰竭患者的预后有良好影响。然而，这些β受体阻滞剂的药理学特征不同。美托洛尔和比索洛尔对β 1-肾上腺素能受体具有选择性，并且没有辅助性质。每日50 mg剂量的卡维地醇阻断所有β 1-、β 2-和α 1-肾上腺素能受体，并具有相关的抗增殖和抗氧化活性。这些差异导致不同的急性血流动力学反应，心输出量减少，选择性药物有肺楔压升高的趋势，卡维地洛无心输出量变化，肺压略有下降。因此，当治疗开始时，最常见的副作用是美托洛尔和比索洛尔的心力衰竭恶化，以及卡维地洛的低血压和头晕。这些差异是否也会影响治疗的长期效果仍然存在争议。与选择性β受体阻滞剂不同，卡维地洛不上调β 1受体，阻断所有肾上腺素能受体，减少心脏去甲肾上腺素释放，从而提供对心脏肾上腺素能驱动的更全面阻断。与选择性β-受体阻滞剂相比，卡维地洛的这些特性导致LV功能的更大增加和最大运动能力的缺乏改善。然而，尚不清楚这些差异是否也会影响患者的结局。
Controlled clinical trials, performed in more than 16,000 patients to date, have consistently shown the beneficial effects of long-term beta-blocker therapy in patients with chronic heart failure. However, it is not clear whether this represents a class effect or it is specific only to some agents. Beneficial effects on the prognosis of the patients with mild to moderate heart failure have been shown with metoprolol, bisoprolol, and carvedilol. However, these beta-blockers differ in their pharmacological characteristics. Metoprolol and bisoprolol are selective for beta 1-adrenergic receptors and are devoid of ancillary properties. Carvediol, at doses of 50 mg daily, blocks all beta 1-, beta 2-, and alpha 1- adrenergic receptors, and has associated antiproliferative and antioxidant activities. These differences cause a different acute hemodynamic response with a reduction in cardiac output and a tendency to a rise in pulmonary wedge pressure with selective agents and no change in cardiac output and a slight decrease in pulmonary pressures with carvedilol. Accordingly, when the therapy is started, the most frequent side effects are worsening heart failure with metoprolol and bisoprolol and hypotension and dizziness with carvedilol. It is still controversial whether these differences may also influence the long-term effects of therapy. Differently from selective beta-blockers, carvedilol does not upregulate beta 1-receptors, blocks all adrenergic receptors, decreases cardiac norepinephrine release, thus providing a more comprehensive blockade of the cardiac adrenergic drive. These properties have caused a larger increase in LV function and a lack of improvement in maximal exercise capacity with carvedilol, compared to selective beta-blockers. It is however, unclear whether these differences may also influence the patients' outcome.