Nottingham University Hospitals NHS Trust (City Campus), Nottingham, UK.
Adv Ther. 2009 Feb;26(2):127-37. doi: 10.1007/s12325-009-0005-x. Epub 2009 Mar 2.
Coronary heart disease is the major cause of morbidity and mortality in industrialized countries, and its prevalence is predicted to grow as the population ages. Current drugs for chronic stable angina (such as beta-blockers, calcium-channel blockers, long- and short-acting nitrates, and potassium-channel activators) are often effective, either as monotherapy or in combination, but side effects and contraindications may limit their use. The "I(f)" (for "funny") channel, discovered in 1979, is expressed mainly in the membrane of pacemaker cells present in the sinus node, the atrioventricular node, the ventricular conduction pathways, and ventricular myocytes. By determining the slope of diastolic depolarization, which in turn controls action potential frequency, it is a key determinant of heart rate and so provides a new therapeutic target for controlling angina symptoms. A new antiangina drug, ivabradine, has been developed and licensed for clinical use. It exclusively reduces the heart rate by selectively blocking the I(f) channel of the sino-atrial node. As clinical trials have shown it to be remarkably well-tolerated, ivabradine offers an alternative for patients who cannot take, or are intolerant of, beta blockade. This review provides an insight into this new agent, its historical background, mechanism of action, and pathophysiologic basis, and provides up-to-date evidence-based information on its optimum use in stable angina.
冠心病是工业化国家发病率和死亡率的主要原因，随着人口老龄化，其患病率预计将会增长。目前用于慢性稳定型心绞痛的药物（如β受体阻滞剂、钙通道阻滞剂、长效和短效硝酸酯类以及钾通道激活剂）通常有效，无论是单独使用还是联合使用，但副作用和禁忌症可能限制其使用。1979 年发现的“i(f)”（“滑稽”）通道主要表达于窦房结、房室结、心室传导途径和心室肌细胞的起搏细胞的膜上。通过确定舒张期去极化的斜率来控制动作电位频率，它是心率的关键决定因素，因此为控制心绞痛症状提供了新的治疗靶点。一种新的抗心绞痛药物伊伐布雷定已经开发并获得临床使用许可。它通过选择性地阻断窦房结的 i(f)通道来专门降低心率。临床试验表明，伊伐布雷定的耐受性非常好，为不能或不耐受β受体阻滞剂的患者提供了一种替代治疗方法。这篇综述深入探讨了这种新药物的背景、作用机制和病理生理基础，并提供了有关其在稳定型心绞痛中的最佳使用的最新循证信息。
