Systematic review of the efficacy and safety of perhexiline in the treatment of ischemic heart disease.
Systematic review of the efficacy and safety of perhexiline in the treatment of ischemic heart disease.
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DOI：
10.2165/00129784-200101030-00005
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发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Krum, H
中科院分区：
文献类型：
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作者：
Killalea, S M;Krum, H
Perhexiline 大约 30 年前推出，并因其在治疗心绞痛方面的功效而迅速赢得声誉。然而，与哌可昔林给药相关的肝脏和神经系统不良反应导致其使用量显着下降。该药物最初被归类为冠状血管扩张剂，后来被归类为钙通道拮抗剂，但最近的数据表明，它通过抑制肉毒碱棕榈酰转移酶-1 (CPT-1) 酶，充当心脏代谢剂。鉴于该药物独特的抗缺血作用和良好的血流动力学特征，加上对该药物不良反应机制的进一步了解以及难治性患者对额外治疗的明确临床需求，perhexiline 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。 Perhexiline 正在考虑在多个国家注册或重新注册，并正在对患有主动脉瓣狭窄和心肌缺血的老年患者进行大规模临床试验进行评估。本系统综述检查了现有已发表文献中与哌克昔林治疗心脏病的功效和耐受性相关的证据。虽然缺乏设计良好的对照试验使用客观终点来确定疗效（几乎所有试验都使用交叉设计，包括少量患者并且对结果进行有限的统计分析），但现有数据一致表明，哌克昔林作为单一疗法比安慰剂更有效。此外，它还可以为那些已经接受最大程度的常规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，通过将血浆哌可昔林浓度保持在治疗范围内（150 至 600 微克/升），可以最大限度地减少不良事件的发生率并保持疗效
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)