Metra M, Nodari S, Dei Cas L
Department of Cardiology, University of Brescia, Brescia, Italy.
Am J Cardiovasc Drugs. 2001;1(1):3-14. doi: 10.2165/00129784-200101010-00001.
Controlled clinical trials performed in more than 13 000 patients have, to date, consistently shown the beneficial effects of long term beta-adrenoceptor antagonist (beta-blocker) therapy in patients with chronic heart failure. It is not clear whether this represents a class effect or whether it is specific only to some agents. Beneficial effects on the prognosis of patients with mild to moderate heart failure have been shown with metoprolol, bisoprolol, and carvedilol. These beta-blockers, however, differ in their pharmacologic characteristics. Metoprolol and bisoprolol are selective for beta(1)-adrenergic receptors and are devoid of ancillary properties. Carvedilol, at a dosage of 50 mg/day, blocks all beta(1)-, beta(2)-, and alpha(1)-adrenergic receptors, and it has associated antiproliferative and antioxidant activities. These differences cause a varied acute hemodynamic response, with a reduction in cardiac output and a tendency toward 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 adverse effects are worsening heart failure with metoprolol and bisoprolol, and hypotension and dizziness with carvedilol. It remains controversial whether these differences also influence the long term effects of therapy. Carvedilol may provide a more comprehensive blockade of the cardiac adrenergic drive than selective beta-blockers because it does not upregulate beta(1)-adrenergic receptors, blocks all adrenergic receptors and decreases cardiac norepinephrine release. These properties may lead to a larger increase in left ventricular function and a lack of improvement in maximal exercise capacity with carvedilol, compared with selective beta-blockers. It is, however, unclear whether these differences also influence patient outcome. The long term effects of different beta-blockers on prognosis are currently being compared in the Carvedilol or Metoprolol European Trial (COMET) in which more than 3000 patients with chronic heart failure have been randomized in a 1 : 1 ratio to receive metoprolol or carvedilol.
迄今为止，在超过13000名患者中进行的对照临床试验一致显示，长期使用β-肾上腺素能受体拮抗剂（β受体阻滞剂）治疗对慢性心力衰竭患者具有有益效果。目前尚不清楚这是类效应还是仅某些药物特有的效应。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作用。然而，这些β受体阻滞剂在药理特性上有所不同。美托洛尔和比索洛尔对β1-肾上腺素能受体具有选择性，且无辅助特性。卡维地洛剂量为50毫克/天时，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降低，肺楔压有升高趋势，而卡维地洛对心输出量无影响，肺压略有下降。因此，开始治疗时，最常见的不良反应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。卡维地洛可能比选择性β受体阻滞剂对心脏肾上腺素能驱动提供更全面的阻断，因为它不会上调β1-肾上腺素能受体，可阻断所有肾上腺素能受体并减少心脏去甲肾上腺素释放。与选择性β受体阻滞剂相比，这些特性可能导致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预后。目前，卡维地洛或美托洛尔欧洲试验（COMET）正在比较不同β受体阻滞剂对预后的长期影响，该试验中，超过3000名慢性心力衰竭患者已按1:1比例随机分组，分别接受美托洛尔或卡维地洛治疗。
