1 Department for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.
2 Department of Medical Biometry and Epidemiology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
J Cardiovasc Pharmacol Ther. 2019 Jan;24(1):62-69. doi: 10.1177/1074248418784290. Epub 2018 Jun 24.
Coronary artery disease is the most prevalent manifestation among cardiovascular diseases. Despite modern treatment, risk of ischemic complications in patients with acute coronary syndrome (ACS) remains important. The late Na current blocker ranolazine has shown to reduce the risk of recurrent ischemia and worsening of angina in patients with non-ST-segment elevation ACS by possibly improving myocardial perfusion, but up to now no trial has addressed whether this enhanced perfusion also leads to a decrease in ischemic myocardium of patients with ACS. We designed a pilot trial (Reduction of Ischemic Myocardium with Ranolazine-Treatment IN patients with acute myocardial Infarction, ClinicalTrials.gov Identifier: NCT01797484) for feasibility and proof of concept that a 6-week ranolazine add-on therapy would reduce the area of ischemic myocardium in patients with ACS.
The trial was designed in a 2-armed, controlled and randomized way. Twenty participants with unstable angina, proof of acute cardiac ischemia, and myocardial dyskinesia by speckle-tracking echocardiography were included. Ten participants received the study drug ranolazine additionally to standard treatment. The control group received standard treatment without additional study medication. Speckle-tracking echocardiography was performed before coronary intervention, before the first dose of ranolazine, and after 6 weeks of ranolazine treatment. Ranolazine was administered safely during acute myocardial infarction. Speckle-tracking echocardiography proved to be suitable for evaluation of myocardial dyskinesia. Patients receiving ranolazine showed a trend to higher normal fraction of the cumulative global strain than patients in the standard treatment group (15% vs 11%). No major complications relating study medication were observed.
In conclusion, in this preliminary hypothesis-driven study, 6-week ranolazine therapy was shown to decrease the area of dyskinetic myocardium in patients with ACS by trend. Global strain rate measurement using speckle-tracking echocardiography can be applied measuring those effects and is, compared to other techniques, safe and harmless. Our data provide a sound basis for a follow-up trial.
冠心病是心血管疾病中最常见的表现形式。尽管有现代治疗方法，但急性冠状动脉综合征（ACS）患者发生缺血性并发症的风险仍然很高。晚期钠电流阻滞剂雷诺嗪已被证明可通过改善心肌灌注来降低非 ST 段抬高型 ACS 患者再次发生缺血和心绞痛恶化的风险，但迄今为止，尚无试验表明这种增强的灌注是否也会导致 ACS 患者的缺血心肌减少。我们设计了一项初步试验（雷诺嗪治疗急性心肌梗死患者缺血性心肌的减少，临床试验.gov 标识符：NCT01797484），以验证 6 周的雷诺嗪附加治疗是否会减少 ACS 患者的缺血性心肌面积。
该试验采用 2 臂、对照和随机设计进行。共纳入 20 名不稳定型心绞痛、斑点追踪超声心动图证实急性心肌缺血和心肌运动障碍的患者。10 名患者在标准治疗的基础上加用研究药物雷诺嗪。对照组接受标准治疗，不给予额外的研究药物。在冠状动脉介入治疗前、首次服用雷诺嗪前和雷诺嗪治疗 6 周后进行斑点追踪超声心动图检查。急性心肌梗死后，雷诺嗪的应用是安全的。斑点追踪超声心动图被证明适用于评估心肌运动障碍。接受雷诺嗪治疗的患者的累积整体应变正常分数趋势高于标准治疗组（15%比 11%）。未观察到与研究药物相关的主要并发症。
总之，在这项初步的假设驱动研究中，6 周的雷诺嗪治疗显示出可降低 ACS 患者的运动障碍性心肌面积的趋势。使用斑点追踪超声心动图测量整体应变率可以用来测量这些效果，与其他技术相比，它是安全无害的。我们的数据为后续试验提供了可靠的基础。
