Elkayam U
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033, USA.
Cardiology. 1998;89 Suppl 1:38-46. doi: 10.1159/000047278.
A considerable effort has been made in the last 15 years to evaluate the safety and efficacy of calcium channel blockers (CCBs) in the treatment of patients with chronic congestive heart failure (CHF). Available studies have provided strong evidence for a potential detrimental effect of the first-generation calcium antagonists in patients with CHF, indicating the need for great caution when these drugs are used in patients with significant depression of left ventricular systolic function. A number of second-generation CCB have demonstrated a strong vasodilatory effect and favorable hemodynamic action but failed to show a similar improvement in exercise capacity, morbidity and mortality. Moreover, drugs such as nicardipine and nisoldipine have resulted in a detrimental effect in some patients and, therefore, cannot be considered safe when used in patients with moderate-to-severe heart failure. Available information from the V-HeFT III study demonstrate a lack of an unfavorable effect of felodipine on exercise tolerance in patients with chronic heart failure. Although mortality rate was similar in both the felodipine and the placebo group, because of the relatively small number of patients in this study, no clear conclusion can be drawn regarding the effect of felodipine on mortality in patients with CHF. An encouraging signal regarding a potential role of CCB in the treatment of chronic heart failure has been provided by the recently completed PRAISE study. This prospective large-scale study demonstrated the safety of amlodipine, a long-acting dihydropyridine derivative, when used in patients with heart failure due to coronary artery disease. Furthermore, this study demonstrated a substantial reduction in mortality in patients with CHF due to nonischemic cardiomyopathy and provided a strong indication for a potential therapeutic benefit of amlodipine when added to standard CHF therapy in this patient population. No clear explanation is available at the present time regarding the reason for the deleterious effect demonstrated with some of the dihydropyridines and the contrasting benefit seen with amlodipine. Finally, more information regarding the safety and efficacy of dihydropyridines should become available in the next year. The PRAISE II study is ongoing and will provide further information regarding the therapeutic role of amlodipine in patients with nonischemic dilated cardiomyopathy. The MACH-1 study is evaluating the effect of mibefradil, a predominant T-type channel blocker with an ideal activity profile, on morbidity and mortality in patients with chronic CHF.
在过去15年里，人们付出了相当大的努力来评估钙通道阻滞剂（CCB）治疗慢性充血性心力衰竭（CHF）患者的安全性和有效性。现有研究提供了有力证据，表明第一代钙拮抗剂对CHF患者可能有有害影响，这表明在左心室收缩功能显著降低的患者中使用这些药物时需格外谨慎。一些第二代CCB已显示出强大的血管舒张作用和良好的血流动力学作用，但未能在运动能力、发病率和死亡率方面表现出类似的改善。此外，尼卡地平和尼索地平等药物在一些患者中产生了有害影响，因此，在中重度心力衰竭患者中使用时不能认为是安全的。V-HeFT III研究的现有信息表明，非洛地平对慢性心力衰竭患者的运动耐量没有不利影响。尽管非洛地平组和安慰剂组的死亡率相似，但由于该研究中的患者数量相对较少，关于非洛地平对CHF患者死亡率的影响无法得出明确结论。最近完成的PRAISE研究提供了一个关于CCB在慢性心力衰竭治疗中潜在作用的令人鼓舞的信号。这项前瞻性大规模研究证明了氨氯地平（一种长效二氢吡啶衍生物）用于冠状动脉疾病所致心力衰竭患者时的安全性。此外，该研究表明，非缺血性心肌病所致CHF患者的死亡率大幅降低，并有力地表明在该患者群体中，氨氯地平添加到标准CHF治疗中可能具有治疗益处。目前尚不清楚一些二氢吡啶类药物显示出有害作用而氨氯地平显示出相反益处的原因。最后，关于二氢吡啶类药物安全性和有效性的更多信息应会在明年获得。PRAISE II研究正在进行中，将提供关于氨氯地平在非缺血性扩张型心肌病患者中治疗作用的进一步信息。MACH-1研究正在评估米贝拉地尔（一种具有理想活性谱的主要T型通道阻滞剂）对慢性CHF患者发病率和死亡率的影响。
