根据一篇发表于4月25 日JAMA 的研究中，研究人员证实雷诺嗪(Ranolazine)可以减少非ST-段抬高型急性冠脉综合征(ACS)患者心肌缺血代谢的有效性研究(MERLIN TIMI-36)。
这项研究一方面提供了雷诺嗪在高危ACS患者中长期应用的安全性数据，另一方面也证实了雷诺嗪在所有ACS导致的心绞痛患者中的有效性。
MERLIN TIMI-36研究是一项安慰剂对照的双盲研究，在17个国家的440个中心，共招募了6560名非ST-段抬高的ACS患者。所有患者都接受了包括阿司匹林、β-阻断剂和口服抗凝药物的标准治疗，还有一部分患者接受了介入治疗或是外科手术。
实验组治疗方案：雷诺嗪200mg静脉滴注1小时，继以80mg/h 的速度静滴96小时；然后口服雷诺嗪1000mg每日两次，持续约12个月。对照组接受同样的静脉滴注和口服治疗方案，但只服用安慰剂。
MERLIN TIMI-36研究结果显示雷诺嗪不能明显降低心源性死亡、心脏病发作和再发性缺血（主要研究终点）的联合发生率，但是却可以单独降低再发性缺血的发生。在接受雷诺嗪治疗的患者中，也没有发生死亡或心律失常的趋势。
雷诺嗪是一种治疗慢性心绞痛的新型抗缺血药物，与其它种类的抗心绞痛药物不同，雷诺嗪对血压和心率没有明显降低作用。在2006年雷诺嗪被批准作为抗心绞痛的二线用药，主要应用于其它抗心绞痛药物治疗无效的患者。这种限制是基于一种理论上安全性的考虑，因为服用雷诺嗪的患者心电图会发生一些微小变化。
MERLIN TIMI-36研究则证实了雷诺嗪对非ST-段抬高ACS患者短期治疗和长期治疗的安全性和有效性。该项研究的负责人，Harvard大学医学院的 David Morrow教授总结说：雷诺嗪在入选的高危患者中显示了其安全性。另外，雷诺嗪组再发性缺血明显减少，为雷诺嗪的抗缺血作用提供了新的证据。
（编译/姜欣慧） (资料来源 : Bio.com)
原始出处:
JAMA, the Journal of the American Medical Association
Vol. 297 No. 16, April 25, 2007
JAMA-EXPRESS
Effects of Ranolazine on Recurrent Cardiovascular Events in Patients With Non–ST-Elevation Acute Coronary Syndromes
The MERLIN-TIMI 36 Randomized Trial
David A. Morrow, MD, MPH; Benjamin M. Scirica, MD, MPH; Ewa Karwatowska-Prokopczuk, MD; Sabina A. Murphy, MPH; Andrzej Budaj, MD; Sergei Varshavsky, MD; Andrew A. Wolff, MD; Allan Skene, PhD; Carolyn H. McCabe, BS; Eugene Braunwald, MD; For the MERLIN-TIMI 36 Trial Investigators
JAMA. 2007;297:1775-1783.
Context Ranolazine is a novel antianginal agent that reduces ischemia in patients with chronic angina but has not been studied in patients with acute coronary syndromes (ACS).
Objective To determine the efficacy and safety of ranolazine during long-term treatment of patients with non–ST-elevation ACS.
Design, Setting, and Patients A randomized, double-blind, placebo-controlled, multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who were treated with ranolazine (initiated intravenously and followed by oral ranolazine extended-release 1000 mg twice daily, n = 3279) or matching placebo (n = 3281), and followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial between October 8, 2004, and February 14, 2007.
Main Outcome Measures The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (MI), or recurrent ischemia through the end of study. The major safety end points were death from any cause and symptomatic documented arrhythmia.
Results The primary end point occurred in 696 patients (21.8%) in the ranolazine group and 753 patients (23.5%) in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.83-1.02; P = .11). The major secondary end point (cardiovascular death, MI, or severe recurrent ischemia) occurred in 602 patients (18.7%) in the ranolazine group and 625 (19.2%) in the placebo group (HR, 0.96; 95% CI, 0.86-1.08; P = .50). Cardiovascular death or MI occurred in 338 patients (10.4%) allocated to ranolazine and 343 patients (10.5%) allocated to placebo (HR, 0.99; 95% CI, 0.85-1.15; P = .87). Recurrent ischemia was reduced in the ranolazine group (430 [13.9%]) compared with the placebo group (494 [16.1%]; HR, 0.87; 95% CI, 0.76-0.99; P = .03). QTc prolongation requiring a reduction in the dose of intravenous drug occurred in 31 patients (0.9%) receiving ranolazine compared with 10 patients (0.3%) receiving placebo. Symptomatic documented arrhythmias did not differ between the ranolazine (99 [3.0%]) and placebo (102 [3.1%]) groups (P = .84). No difference in total mortality was observed with ranolazine compared with placebo (172 vs 175; HR, 0.99; 95% CI, 0.80-1.22; P = .91).
Conclusions The addition of ranolazine to standard treatment for ACS was not effective in reducing major cardiovascular events. Ranolazine did not adversely affect the risk of all-cause death or symptomatic documented arrhythmia. Our findings provide support for the safety and efficacy of ranolazine as antianginal therapy.
Trial Registration clinicaltrials.gov Identifier: NCT00099788
Author Affiliations: TIMI Study Group, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass (Drs Morrow, Scirica, and Braunwald, and Mss Murphy and McCabe); CV Therapeutics, Palo Alto, Calif (Dr Karwatowska-Prokopczuk); Postgraduate Medical School, Department of Cardiology, Grochowski Hospital, Warsaw, Poland (Dr Budaj); Evidence Clinical and Pharmaceutical Research, St Petersburg, Russia (Dr Varshavsky); Cytokinetics, San Francisco, Calif (Dr Wolff); and Nottingham Clinical Research Limited, Nottingham, United Kingdom (Dr Skene).
