雷诺嗪是一种具有新型电生理特性的抗心绞痛药物，对非ST段抬高型急性冠状动脉综合征患者心律失常发生率的影响：来自非ST段抬高型急性冠状动脉综合征心肌梗死溶栓36（MERLIN-TIMI 36）随机对照试验中雷诺嗪降低缺血代谢效率的结果。

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: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial.

作者信息

Scirica Benjamin M, Morrow David A, Hod Hanoch, Murphy Sabina A, Belardinelli Luiz, Hedgepeth Chester M, Molhoek Peter, Verheugt Freek W A, Gersh Bernard J, McCabe Carolyn H, Braunwald Eugene

机构信息

TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.

出版信息

Circulation. 2007 Oct 9;116(15):1647-52. doi: 10.1161/CIRCULATIONAHA.107.724880. Epub 2007 Sep 5.

DOI:10.1161/CIRCULATIONAHA.107.724880

PMID:17804441

Abstract

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 > or = 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 > or = 3 seconds were less frequent with ranolazine (97 [3.1%] versus 136 [4.3%]; P=0.01).

CONCLUSIONS

Ranolazine, an inhibitor of late I(Na), 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.

摘要

背景

雷诺嗪是一种哌嗪衍生物，通过抑制心脏复极期间内向钠电流的晚期（晚期I(Na)）来减轻缺血，从而减少细胞内钠和钙超载。细胞内钙增加会导致机械功能障碍和电不稳定。在实验模型中，雷诺嗪可减少促心律失常底物和触发因素，如早期后去极化。然而，雷诺嗪潜在的抗心律失常作用尚未在人类中得到证实。

方法与结果

非ST段抬高急性冠状动脉综合征中雷诺嗪降低缺血的代谢效率（MERLIN）-心肌梗死溶栓（TIMI）36（MERLIN-TIMI 36）试验将6560例因非ST段抬高急性冠状动脉综合征住院的患者随机分为雷诺嗪组或安慰剂组，同时给予标准治疗。随机分组后的前7天进行连续心电图（动态心电图）记录。由对治疗和结果不知情的核心实验室评估一组预先设定的心律失常。在MERLIN-TIMI 36试验的6560例患者中，6351例（97%）有可用于心律失常分析的连续心电图记录。雷诺嗪治疗使心律失常的发生率显著降低。具体而言，持续≥8次搏动的室性心动过速发作的患者较少（166例[5.3%]对265例[8.3%]；P<0.001），室上性心动过速（1413例[44.7%]对1752例[55.0%]；P<0.001），或新发心房颤动（分别为55例[1.7%]和75例[2.4%]；P=0.08）。此外，雷诺嗪治疗时≥3秒的停搏较少见（97例[3.1%]对136例[4.3%]；P=0.01）。