Melloni Chiara, Newby L Kristin
Duke Clinical Research Institute, 2400 Pratt Street, Durham, NC 27705, USA.
Expert Rev Cardiovasc Ther. 2008 Jan;6(1):9-16. doi: 10.1586/14779072.6.1.9.
Ranolazine is a piperazine derivative believed to reduce anginal symptoms by preventing ischemia-mediated sodium and calcium overload in myocardial cells through inhibition of the late sodium current (late INa). Three small studies demonstrated the antianginal efficacy of ranolazine alone and in combination with betablockers or calcium channel blockers on conventional end points such as total exercise duration and time to ischemia/angina on a treadmill; however, questions of safety related to QT prolongation, efficacy in women and potential utility in higher risk populations remained. Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes-Thrombolysis in Myocardial Infarction (MERLIN-TIMI) 36 was a large randomized, double-blind, placebo-controlled trial, which evaluated the efficacy and safety of ranolazine initiated acutely and continued as chronic therapy following a non-ST-segment elevation acute coronary syndrome event. A total of 6560 patients were randomized 1:1 to ranolazine or placebo; the primary efficacy end point of the trial was a composite of cardiovascular death, myocardial infarction or recurrent ischemia. The key safety end points were death from any cause and symptomatic documented arrhythmia. Although statistically significant differences between the ranolazine and placebo groups were not reached in the primary efficacy analysis or in the major secondary outcome end point analyses (cardiovascular death, myocardial infarction or severe recurrent ischemia), the individual component of recurrent ischemia was significantly reduced by ranolazine, and ranolazine was demonstrated to be safe.
雷诺嗪是一种哌嗪衍生物，据信它可通过抑制晚钠电流（late INa）来防止缺血介导的心肌细胞钠和钙超载，从而减轻心绞痛症状。三项小型研究证明了雷诺嗪单独使用以及与β受体阻滞剂或钙通道阻滞剂联合使用时，在常规终点指标（如总运动持续时间以及跑步机上出现缺血/心绞痛的时间）方面的抗心绞痛疗效；然而，与QT间期延长相关的安全性问题、在女性中的疗效以及在高风险人群中的潜在效用等问题依然存在。非ST段抬高急性冠状动脉综合征中使用雷诺嗪提高代谢效率减少缺血——心肌梗死溶栓（MERLIN-TIMI）36试验是一项大型随机、双盲、安慰剂对照试验，该试验评估了在非ST段抬高急性冠状动脉综合征事件后急性起始并持续作为长期治疗的雷诺嗪的疗效和安全性。共有6560例患者按一比一随机分配至雷诺嗪组或安慰剂组；该试验的主要疗效终点是心血管死亡、心肌梗死或复发性缺血的复合终点。关键安全性终点是任何原因导致的死亡以及有症状记录的心律失常。尽管在主要疗效分析或主要次要结局终点分析（心血管死亡、心肌梗死或严重复发性缺血）中，雷诺嗪组和安慰剂组之间未达到统计学显著差异，但雷诺嗪使复发性缺血的单项指标显著降低，并且证明雷诺嗪是安全的。
