Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of Arrhythmias in patients with Non-ST-Segment-Elevation acute coronary syndrome - Thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36) Randomized controlled trial
Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of Arrhythmias in patients with Non-ST-Segment-Elevation acute coronary syndrome - Thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36) Randomized controlled trial
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DOI：
10.1161/circulationaha.107.724880
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发表时间：
2007-10-09
期刊：
影响因子：
37.8
通讯作者：
Braunwald, Eugene
中科院分区：
文献类型：
--
作者：
Scirica, Benjamin M.;Morrow, David A.;Braunwald, Eugene
背景-雷诺嗪是一种哌嗪衍生物，通过抑制心脏复极过程中内向钠电流的晚期（晚期I-Na），从而减少细胞内钠和钙超载，从而减少缺血。细胞内钙增加导致机械功能障碍和电不稳定。在实验模型中，雷诺嗪可减少促肾上腺皮质激素底物和触发因素，如早期后去极化。然而，在这方面，雷诺嗪的潜在抗心律失常作用尚未在人体中得到证实。方法和结果-雷诺嗪对非ST段抬高急性冠状动脉综合征（MERLIN）缺血较少的代谢效率-心肌梗死溶栓（TIMI）36（MERLIN-TIMI 36）试验将6560例非ST段抬高急性冠脉综合征住院患者随机分为雷诺嗪组和安慰剂组。随机化后前7天进行连续ECG（霍尔特）记录。由对治疗和结局设盲的核心实验室对预先设定的心律失常进行评价。在MERLIN-TIMI 36的6560例患者中，6351例（97%）有连续ECG记录，可用于心律失常分析。雷诺嗪治疗导致心律失常的发生率显著降低。特别是，较少的患者发生持续≥ 8次的室性心动过速（166 [5.3%] vs 265 [8.3%]; P < 0.001），室上性心动过速（1413例[ 44.7%]对1752例[ 55.0%]; P < 0.001）或新发房颤（55例[ 1.7%]对75例[ 2.4%]; P = 0.08）。此外，雷诺嗪组暂停≥ 3秒的频率较低（97 [ 3.1%] vs 136 [ 4.3%]; P = 0.01）。结论：雷诺嗪是一种迟发性INa抑制剂，通过对急性冠脉综合征患者入院后第一周的连续心电图监测评估，似乎具有抗心律失常作用。有必要进行专门设计的研究，以评估雷诺嗪作为抗肿瘤药物的潜在作用。
Background - Ranolazine, a piperazine derivative, reduces ischemia via inhibition of the late phase of the inward sodium current (late I-Na) during cardiac repolarization, with a consequent reduction in intracellular sodium and calcium overload. Increased intracellular calcium leads to both mechanical dysfunction and electric instability. Ranolazine reduces proarrhythmic substrate and triggers such as early afterdepolarization in experimental models. However, the potential antiarrhythmic actions of ranolazine have yet to be demonstrated in humans.Methods and Results - The Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST- Elevation Acute Coronary Syndrome ( MERLIN) - Thrombolysis in Myocardial Infarction ( TIMI) 36 ( MERLIN- TIMI 36) trial randomized 6560 patients hospitalized with a non-ST- elevation acute coronary syndrome to ranolazine or placebo in addition to standard therapy. Continuous ECG ( Holter) recording was performed for the first 7 days after randomization. A prespecified set of arrhythmias were evaluated by a core laboratory blinded to treatment and outcomes. Of the 6560 patients in MERLIN- TIMI 36, 6351 ( 97%) had continuous ECG recordings that could be evaluated for arrhythmia analysis. Treatment with ranolazine resulted in significantly lower incidences of arrhythmias. Specifically, fewer patients had an episode of ventricular tachycardia lasting >= 8 beats ( 166 [5.3%] versus 265 [8.3%]; P < 0.001), supraventricular tachycardia ( 1413 [ 44.7%] versus 1752 [ 55.0%]; P < 0.001), or new- onset atrial fibrillation ( 55 [ 1.7%] versus 75 [ 2.4%]; P = 0.08). In addition, pauses >= 3 seconds were less frequent with ranolazine ( 97 [ 3.1%] versus 136 [ 4.3%]; P = 0.01).Conclusions - Ranolazine, an inhibitor of late INa, appears to have antiarrhythmic effects as assessed by continuous ECG monitoring of patients in the first week after admission for acute coronary syndrome. Studies specifically designed to evaluate the potential role of ranolazine as an antiarrhythmic agent are warranted.