Metra Marco, Nodari Savina, Bignotti Tommaso, Gnesin Paolo, Trussardi Elena, Cas Livio Dei
Cattedra di Cardiologia, Università, Brescia.
Recenti Prog Med. 2002 Feb;93(2):113-24.
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.
迄今为止,针对超过16000名患者进行的对照临床试验一直表明,长期使用β受体阻滞剂治疗对慢性心力衰竭患者具有有益效果。然而,尚不清楚这是一种类效应,还是仅特定于某些药物。美托洛尔、比索洛尔和卡维地洛已显示出对轻至中度心力衰竭患者预后的有益影响。然而,这些β受体阻滞剂在药理特性上存在差异。美托洛尔和比索洛尔对β1肾上腺素能受体具有选择性,且无附加特性。卡维地洛每日剂量为50毫克时,可阻断所有β1、β2和α1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,选择性药物会使心输出量减少,肺楔压有升高趋势,而卡维地洛则使心输出量无变化,肺压力略有下降。因此,在开始治疗时,最常见的副作用是美托洛尔和比索洛尔导致心力衰竭恶化,卡维地洛导致低血压和头晕。这些差异是否也会影响治疗的长期效果仍存在争议。与选择性β受体阻滞剂不同,卡维地洛不会上调β1受体,可阻断所有肾上腺素能受体,减少心脏去甲肾上腺素释放,从而更全面地阻断心脏肾上腺素能驱动。与选择性β受体阻滞剂相比,这些特性使卡维地洛使左心室功能有更大改善,但最大运动能力无改善。然而,尚不清楚这些差异是否也会影响患者的预后。