Sulfi S, Timmis A D
Department Cardiology, London Chest Hospital, London, UK.
Int J Clin Pract. 2006 Feb;60(2):222-8. doi: 10.1111/j.1742-1241.2006.00817.x.
Heart rate, a major determinant of angina in coronary disease, is also an important predictor of cardiovascular mortality. Lowering heart rate is therefore one of the most important therapeutic approaches in the treatment of stable angina pectoris. To date, beta-blockers and some calcium-channel antagonists reduce heart rate, but their use may be limited by adverse reactions or contraindications. Heart rate is determined by spontaneous electrical pacemaker activity in the sinoatrial node controlled by the I(f) current. Ivabradine is the first specific heart rate-lowering agent that has completed clinical development for stable angina pectoris. It is selective for the I(f) current, lowering heart rate at concentrations that do not affect other cardiac ionic currents. Specific heart-rate lowering with ivabradine reduces myocardial oxygen demand, simultaneously improving oxygen supply. Ivabradine has no negative inotropic or lusitropic effects, preserving ventricular contractility, and does not change any major electrophysiological parameters unrelated to heart rate. Randomised clinical studies in patients with stable angina show that ivabradine effectively reduces heart rate, improves exercise capacity and reduces the number of angina attacks. It has superior anti-anginal and anti-ischaemic activity to placebo and is non-inferior to atenolol and amlodipine. Ivabradine therefore offers a valuable approach to lowering heart rate exclusively and provides an attractive alternative to conventional treatment for a wide range of patients with confirmed stable angina.
心率是冠心病心绞痛的主要决定因素，也是心血管疾病死亡率的重要预测指标。因此，降低心率是治疗稳定型心绞痛最重要的治疗方法之一。迄今为止，β受体阻滞剂和一些钙通道拮抗剂可降低心率，但它们的使用可能会受到不良反应或禁忌症的限制。心率由受I(f)电流控制的窦房结自发电起搏活动决定。伊伐布雷定是首个完成稳定型心绞痛临床开发的特异性降低心率药物。它对I(f)电流具有选择性，能在不影响其他心脏离子电流的浓度下降低心率。伊伐布雷定特异性降低心率可减少心肌需氧量，同时改善氧供应。伊伐布雷定没有负性肌力或负性变时作用，可保持心室收缩力，且不改变任何与心率无关的主要电生理参数。对稳定型心绞痛患者的随机临床研究表明，伊伐布雷定可有效降低心率、提高运动能力并减少心绞痛发作次数。其抗心绞痛和抗缺血活性优于安慰剂，且不劣于阿替洛尔和氨氯地平。因此，伊伐布雷定提供了一种专门降低心率的有效方法，并为广泛确诊的稳定型心绞痛患者提供了一种有吸引力的传统治疗替代方案。
