Swedberg K
Department of Medicine, Sahlgrenska University Hospital/Ostra, Göteborg, Sweden.
Blood Press Suppl. 2000;1:44-8.
Heart failure remains a major and increasing cause of mortality and morbidity, even when the best available treatments are used. One of its key causes is neuroendocrine activation via the sympathetic nervous system and the renin-angiotensin system (RAS). Neuroendocrine blockers of the sympathetic nervous system (beta-blockers) and of the RAS (angiotensin-converting enzyme [ACE] inhibitors and angiotensin II type 1 [AT1] receptor blockers) therefore have an important potential therapeutic role in heart failure. The promising results from clinical trials with beta-blockers suggest that these drugs will become an established part of the future management of patients with mild to moderate symptomatic heart failure. Blockade of the RAS with ACE inhibitors has also been shown to be effective in reducing the risk of morbidity and mortality in patients with heart failure. Blockade of the AT1-receptor, with agents such as candesartan, produces more specific and, theoretically, more complete blockade of the major negative cardiovascular effects of angiotensin II than is possible using ACE inhibitors, whilst maintaining placebo-like tolerability. Furthermore, AT1-receptor blockade leads to increased stimulation of the angiotensin II type 2 (AT2) receptor, which, according to experimental data, may have favourable cardiovascular effects. Following encouraging results from two pilot studies, a major new international study programme - CHARM (Candesartan in Heart failure - Assessment of Reduction in Mortality and morbidity) - has been initiated to define the clinical benefits of candesartan cilexetil in a wide variety of patients with symptomatic heart failure. CHARM is the first study to accept all relevant heart failure patients who may benefit from RAS blockade, irrespective of their left ventricular function or tolerance of ACE inhibitors. The 6500 patients to be recruited will be divided among three integrated outcome studies. Two of these studies will examine the effect of candesartan cilexetil versus placebo in patients with an ejection fraction of 40% or less who are tolerant or intolerant of ACE inhibitors. The third study arm will examine the benefits of candesartan cilexetil in a previously seldom studied group: those with symptomatic heart failure, but with preserved left-ventricular systolic function. Recruitment of patients into the study has started.
心力衰竭仍然是导致死亡和发病的主要且日益严重的原因，即便使用了现有的最佳治疗方法亦是如此。其关键病因之一是通过交感神经系统和肾素 - 血管紧张素系统（RAS）引发的神经内分泌激活。因此，交感神经系统的神经内分泌阻滞剂（β受体阻滞剂）以及RAS的阻滞剂（血管紧张素转换酶[ACE]抑制剂和血管紧张素II 1型[AT1]受体阻滞剂）在心力衰竭治疗中具有重要的潜在治疗作用。β受体阻滞剂临床试验取得的喜人结果表明，这些药物将成为未来轻至中度症状性心力衰竭患者管理的既定组成部分。ACE抑制剂对RAS的阻断也已被证明可有效降低心力衰竭患者发病和死亡的风险。使用坎地沙坦等药物阻断AT1受体，与使用ACE抑制剂相比，能更特异性地、理论上更完全地阻断血管紧张素II的主要负面心血管效应，同时保持类似安慰剂的耐受性。此外，AT1受体阻断会导致血管紧张素II 2型（AT2）受体的刺激增加，根据实验数据，这可能具有有利的心血管效应。在两项试点研究取得令人鼓舞的结果后，一项重大的新国际研究项目——CHARM（坎地沙坦治疗心力衰竭——降低死亡率和发病率评估）已启动，以确定坎地沙坦酯在各类症状性心力衰竭患者中的临床益处。CHARM是首个接受所有可能从RAS阻断中获益的相关心力衰竭患者的研究，无论其左心室功能或对ACE抑制剂的耐受性如何。即将招募的6500名患者将被分配到三项综合结局研究中。其中两项研究将考察坎地沙坦酯与安慰剂对射血分数为40%或更低、对ACE抑制剂耐受或不耐受的患者的效果。第三个研究组将考察坎地沙坦酯对一个此前很少研究的群体的益处：有症状性心力衰竭但左心室收缩功能保留的患者。患者招募工作已开始。
