Cardiovascular Division, Brigham & Women’s Hospital, Boston, Massachusetts 02115, USA.
J Am Coll Cardiol. 2010 Sep 14;56(12):934-42. doi: 10.1016/j.jacc.2010.04.042.
The purpose of this explanatory analysis was to investigate the relationship between ST-segment depression and the rate-pressure product (RPP) during exercise to determine whether ranolazine's mechanism of action was related to a reduction in myocardial oxygen demand or preservation of myocardial oxygen supply.
In patients with stable ischemic heart disease, ranolazine increases exercise duration and reduces maximal ST-segment depression while exerting minimal effects on heart rate and blood pressure, although its mechanism of action during exercise has not been investigated.
Patients with stable ischemic heart disease (n = 191) were randomly allocated to a 4-period, double-blind, balanced Latin square crossover study to receive placebo, and ranolazine 500, 1,000, and 1,500 mg twice daily (bid) for 1 week each. Exercise treadmill tests were performed at baseline and at the end of each treatment period. The RPP and ST-segment depression were assessed before starting exercise, at each stage of exercise, and at maximal exercise.
Compared with placebo, ranolazine produced a dose-dependent reduction in ST-segment depression that became more marked as exercise-induced ischemia became more pronounced, associated with clinically minor decreases in heart rate and blood pressure. At 12-min exercise, the amount of ST-segment depression compared with placebo and controlled for RPP was reduced by 22.3% on ranolazine 500 mg bid (p = 0.137), by 35.4% on 1,000 mg bid (p = 0.005), and by 45.8% on 1,500 mg bid (p < 0.001).
The progressive magnitude of ischemia reduction on ranolazine was proportionally more substantial than the minor reductions in heart rate or RPP, suggesting that ranolazine's beneficial mechanism of action is most likely primarily due to an improvement in regional coronary blood flow in areas of myocardial ischemia.
本解释性分析旨在研究运动期间 ST 段压低与心率-压力乘积（RPP）之间的关系，以确定雷诺嗪的作用机制是否与降低心肌需氧量或维持心肌氧供有关。
在稳定性缺血性心脏病患者中，雷诺嗪增加运动时间并减少最大 ST 段压低，同时对心率和血压影响最小，尽管其在运动期间的作用机制尚未得到研究。
将稳定性缺血性心脏病患者（n=191）随机分配至 4 期、双盲、平衡拉丁方交叉研究，分别接受安慰剂和雷诺嗪 500、1000 和 1500 mg 每日 2 次（bid）治疗 1 周。在基线和每个治疗期结束时进行运动平板测试。在开始运动前、运动各阶段和最大运动时评估 RPP 和 ST 段压低。
与安慰剂相比，雷诺嗪呈剂量依赖性降低 ST 段压低，随着运动诱导缺血加重，压低程度更加明显，同时心率和血压有临床意义的轻度下降。在 12 分钟运动时，与安慰剂相比，雷诺嗪 500 mg bid 组的 ST 段压低程度降低了 22.3%（p=0.137），1000 mg bid 组降低了 35.4%（p=0.005），1500 mg bid 组降低了 45.8%（p<0.001），且与 RPP 呈负相关。
雷诺嗪减轻缺血的程度呈进行性增加，而心率或 RPP 的降低幅度较小，提示雷诺嗪的有益作用机制主要是通过改善心肌缺血区域的局部冠状动脉血流来实现的。
