Diaz Ariel, Tardif Jean-Claude
Montreal Heart Institute, Montreal, Canada.
Adv Cardiol. 2006;43:65-78. doi: 10.1159/000095429.
Relieving the symptoms of angina and improving the quality of life and functional status are important objectives in the management of patients with chronic stable angina. A high heart rate induces or exacerbates myocardial ischemia and angina because it both increases oxygen demand and decreases myocardial perfusion. Beta-Blockers are effective at reducing anginal symptoms largely by decreasing heart rate. Physician use and patient compliance may be limited by the side effects of Beta-blockers which include fatigue, depression and sexual dysfunction. Heart rate reduction can also be obtained by the calcium antagonists verapamil and diltiazem and by the new selective heart-rate-reducing agent ivabradine. Ivabradine (Procoralan) is a selective and specific I(f) inhibitor that acts on one of the most important ionic currents for the regulation of the pacemaker activity of sinoatrial node cells. Ivabradine has demonstrated dosedependent anti-ischemic and antianginal effects in a placebo-controlled study. The INITIATIVE trial is a large multicenter trial in which 939 patients with stable angina were randomized to ivabradine or atenolol. The noninferiority of ivabradine was shown in the INITIATIVE trial at all doses and for all criteria including time to limiting angina. The number of angina attacks per week was decreased by two thirds with both ivabradine and atenolol. In another trial of 1,195 patients, time to 1mm ST segment depression was increased by 45 s with ivabradine 7.5 mg b.i.d. and by 40 s with amlodipine 10 mg daily. Unlike beta-blockers, ivabradine is devoid of intrinsic negative inotropic effects and does not affect coronary vasomotion. A whole range of patients with angina may benefit from exclusive heart rate reduction with ivabradine, including those with contraindications or intolerance to the use of beta-blockers and patients that are insufficiently controlled by beta-blockers or calcium channel blockers.
缓解心绞痛症状、改善生活质量和功能状态是慢性稳定型心绞痛患者管理中的重要目标。心率过快会诱发或加重心肌缺血和心绞痛，因为它既增加了氧需求，又减少了心肌灌注。β受体阻滞剂主要通过降低心率来有效减轻心绞痛症状。β受体阻滞剂的副作用（包括疲劳、抑郁和性功能障碍）可能会限制医生的使用和患者的依从性。钙拮抗剂维拉帕米和地尔硫䓬以及新型选择性心率降低剂伊伐布雷定也可降低心率。伊伐布雷定（可兰特）是一种选择性、特异性的I(f)抑制剂，作用于调节窦房结细胞起搏活动的最重要离子电流之一。在一项安慰剂对照研究中，伊伐布雷定已显示出剂量依赖性的抗缺血和抗心绞痛作用。INITIATIVE试验是一项大型多中心试验，939例稳定型心绞痛患者被随机分为伊伐布雷定组或阿替洛尔组。在INITIATIVE试验中，伊伐布雷定在所有剂量和所有标准（包括至限定性心绞痛的时间）下均显示出非劣效性。伊伐布雷定和阿替洛尔均可使每周心绞痛发作次数减少三分之二。在另一项针对1195例患者的试验中，伊伐布雷定7.5 mg每日两次可使至ST段压低1mm的时间延长45秒，氨氯地平10 mg每日一次可使该时间延长40秒。与β受体阻滞剂不同，伊伐布雷定没有内在的负性肌力作用，也不影响冠状动脉血管运动。包括那些有β受体阻滞剂使用禁忌证或不耐受以及β受体阻滞剂或钙通道阻滞剂控制不佳的患者在内，各类心绞痛患者都可能从单纯使用伊伐布雷定降低心率中获益。
