Prescrire Int. 2007 Apr;16(88):53-6.
(1) The first-line symptomatic treatment for stable angina is a betablocker such as atenolol. Some calcium channel blockers such as verapamil, and the potassium channel agonist amlodipine, are second-line alternatives. Long-acting nitrate derivatives have poorly documented efficacy but can be used as adjuvants or as third-line treatments. (2) Ivabradine is derived from verapamil but appears to have a different mechanism of action, mainly lowering the heart rate. It was approved for sale in Europe through the centralised procedure for second-line treatment of stable angina. (3) Clinical evaluation of ivabradine only includes randomised controlled trials versus two other anti-angina drugs: atenolol and amlodipine. Three double-blind randomised controlled trials lasting 3 to 4 months, based on surrogate exercise endpoints, failed to show that ivabradine was any more effective than atenolol or amlodipine, or even more effective than placebo in patients already treated with amlodipine. (4) In two one-year double-blind randomised controlled trials comparing ivabradine with atenolol or amlodipine in a total of 704 patients, ivabradine was no more effective than the comparators in preventing angina attacks. (5) In head-to-head comparisons, serious coronary events were significantly more frequent with ivabradine than with atenolol (3.8% versus 1.5%). Severe arrhythmias were also more frequent with ivabradine than with atenolol (1.3% versus 0.7%) or amlodipine (0.6% versus 0.2%). (6) Ivabradine provokes phosphenes (flashing lights, etc.) in about 17% of patients in the short term. Information is inadequate to assess possible risks of retinal toxicity in the long term. (7) Ivabradine is metabolised by cytochrome P450 isoenzyme CYP 3A4; there is therefore a potentially high risk of pharmacokinetic interactions. (8) In practice, for long-term preventive treatment of angina it is better to avoid ivabradine and to use better-documented treatments: preferably a betablocker, or, if a betablocker cannot be used, verapamil or amlodipine.
(1) 稳定型心绞痛的一线对症治疗药物是β受体阻滞剂，如阿替洛尔。一些钙通道阻滞剂，如维拉帕米，以及钾通道激动剂氨氯地平，是二线替代药物。长效硝酸盐衍生物的疗效记录不佳，但可作为辅助药物或三线治疗药物使用。(2) 伊伐布雷定由维拉帕米衍生而来，但作用机制似乎不同，主要是降低心率。它通过集中程序在欧洲获批用于稳定型心绞痛的二线治疗。(3) 伊伐布雷定的临床评估仅包括与另外两种抗心绞痛药物阿替洛尔和氨氯地平的随机对照试验。三项基于替代运动终点、为期3至4个月的双盲随机对照试验未能表明伊伐布雷定比阿替洛尔或氨氯地平更有效，甚至在已接受氨氯地平治疗的患者中也不比安慰剂更有效。(4) 在两项为期一年的双盲随机对照试验中，将伊伐布雷定与阿替洛尔或氨氯地平在总共704例患者中进行比较，伊伐布雷定在预防心绞痛发作方面并不比对照药物更有效。(5) 在直接比较中，伊伐布雷定导致的严重冠状动脉事件明显比阿替洛尔更频繁（3.8% 对1.5%）。严重心律失常在伊伐布雷定组中也比阿替洛尔组（1.3% 对0.7%）或氨氯地平组（0.6% 对0.2%）更频繁。(6) 伊伐布雷定在短期内约17% 的患者中会引发光幻视（闪光等）。长期视网膜毒性的潜在风险信息不足。(7) 伊伐布雷定由细胞色素P450同工酶CYP 3A4代谢；因此存在潜在的高药代动力学相互作用风险。(8) 在实践中，对于心绞痛的长期预防性治疗，最好避免使用伊伐布雷定，而使用记录更完善的治疗方法：首选β受体阻滞剂，或者，如果不能使用β受体阻滞剂，则使用维拉帕米或氨氯地平。
