Killalea S M, Krum H
Clinical Pharmacology Unit, Department of Epidemiology and Preventive Medicine/Department of Medicine, Monash University, Prahran, Victoria, Australia.
Am J Cardiovasc Drugs. 2001;1(3):193-204. doi: 10.2165/00129784-200101030-00005.
Perhexiline was introduced about 30 years ago and rapidly gained a reputation for efficacy in the management of angina pectoris. However, hepatic and neurological adverse effects associated with perhexiline administration led to a marked decline in its use. The drug was originally classified as a coronary vasodilator, and later as a calcium channel antagonist, but recent data suggests that it acts as a cardiac metabolic agent, through inhibition of the enzyme, carnitine palmitoyltransferase-1 (CPT-1). Given the drug's unique anti-ischemic action and favorable hemodynamic profile, together with an improved understanding of the mechanisms underlying the adverse effects of the drug and the clear clinical need for additional therapies in refractory patients, perhexiline is currently being re-appraised as a potentially useful agent in the management of severe myocardial ischemia. Perhexiline is being considered for registration or re-registration in a number of countries and is being evaluated in a large-scale clinical trial in elderly patients with aortic stenosis and myocardial ischemia. This systematic review examines the evidence from available published literature in relation to the efficacy and tolerability of perhexiline in the treatment of cardiac disease. While there is a lack of well designed controlled trials using objective end-points to determine efficacy (almost all trials used a crossover design, included small numbers of patients and had limited statistical analysis of results), there is consistency in the data available that perhexiline is considerably more effective than placebo when used as monotherapy. Furthermore, it affords additional symptom relief in those already receiving maximal conventional anti-anginal therapy. However, there is a paucity of trials demonstrating the efficacy of low dosages of perhexiline (100 to 200 mg/day) in patients with refractory angina pectoris. Available evidence also suggests that the incidence of adverse events can be minimised, and the efficacy maintained, by keeping plasma perhexiline concentrations within a therapeutic range (150 to 600 micro g/L)
哌克昔林大约在30年前被引入，在心绞痛的治疗中迅速赢得了疗效显著的声誉。然而，与哌克昔林给药相关的肝脏和神经不良反应导致其使用量显著下降。该药物最初被归类为冠状血管扩张剂，后来又被归类为钙通道拮抗剂，但最近的数据表明，它通过抑制肉碱棕榈酰转移酶-1（CPT-1）发挥心脏代谢剂的作用。鉴于该药物独特的抗缺血作用和良好的血流动力学特征，以及对该药物不良反应潜在机制的进一步了解，同时考虑到难治性患者对额外治疗的明确临床需求，哌克昔林目前正在被重新评估为治疗严重心肌缺血的潜在有用药物。多个国家正在考虑对哌克昔林进行注册或重新注册，并且正在针对患有主动脉瓣狭窄和心肌缺血的老年患者开展一项大规模临床试验对其进行评估。本系统评价审查了现有已发表文献中有关哌克昔林治疗心脏病的疗效和耐受性的证据。虽然缺乏使用客观终点来确定疗效的精心设计的对照试验（几乎所有试验都采用交叉设计，纳入患者数量少且对结果的统计分析有限），但现有数据一致表明，哌克昔林作为单一疗法使用时比安慰剂有效得多。此外，它能为那些已经接受最大剂量传统抗心绞痛治疗的患者提供额外的症状缓解。然而，很少有试验证明低剂量哌克昔林（100至200毫克/天）对难治性心绞痛患者的疗效。现有证据还表明，通过将血浆哌克昔林浓度保持在治疗范围内（150至600微克/升），不良事件的发生率可以降至最低，并维持疗效。
