意大利费拉拉大学Roberto Ferrari团队研究了曲美他嗪治疗成功接受经皮冠状动脉介入治疗患者的疗效和安全性。2020年8月30日，该研究发表在《柳叶刀》杂志上。

尽管经皮冠状动脉介入治疗（PCI）和抗心绞痛疗法成功进行了血管重建，但心绞痛仍可能持续或复发。此外，与最佳药物治疗相比，PCI治疗稳定型患者尚无证据表明可改善生存率。曲美他嗪是一种抗心绞痛药，可改善缺血性心肌的能量代谢，并可改善近期有PCI患者的预后和症状。

为了评估标准循证医学治疗联合曲美他嗪治疗近期成功接受PCI患者的长期潜在益处和安全性，研究组在欧洲、南美、亚洲和北非的27个国家/地区的365个中心进行了一项随机、双盲、安慰剂对照、事件驱动试验。

2014年9月17日至2016年6月15日，研究组共招募了6007例年龄为21-85岁、1个月内接受过选择性PCI治疗稳定型心绞痛或紧急PCI治疗不稳定型心绞痛或非ST段抬高型心肌梗塞的患者。将其随机分组，其中2998例接受曲美他嗪治疗，3009例接受安慰剂治疗。主要疗效终点为心脏性死亡；因心脏事件入院；心绞痛复发或持续，需要加量、换药或增加至少一种抗心绞痛药物的剂量；心绞痛复发或持续需要冠状动脉造影的综合结局。

中位随访47.5个月后，曲美他嗪组中有23.3%的患者发生主要疗效终点，安慰剂组中有23.7%，风险比为0.98。单独分析时，两组间主要终点各事件的发生率无显著差异。选择性PCI患者和紧急PCI患者间亦无显著差异。曲美他嗪组2983例患者中有1219例（40.9%）出现因治疗引起的严重不良事件，安慰剂组2990例患者中有1230例（41.1%），两组间不良事件的发生率无显著差异。

研究结果表明，对于接受最佳药物治疗的成功接受PCI的患者，在几年内常规服用曲美他嗪并不会改善心绞痛的复发或预后。

附：英文原文

Title: Efficacy and safety of trimetazidine after percutaneous coronary intervention (ATPCI): a randomised, double-blind, placebo-controlled trial

Author: Roberto Ferrari, Ian Ford, Kim Fox, Jean Pascal Challeton, Anne Correges, Michal Tendera, Petr Widimsky, Nicolas Danchin

Issue&Volume: 2020-08-30

Abstract: Background

Angina might persist or reoccur despite successful revascularisation with percutaneous coronary intervention (PCI) and antianginal therapy. Additionally, PCI in stable patients has not been shown to improve survival compared with optimal medical therapy. Trimetazidine is an antianginal agent that improves energy metabolism of the ischaemic myocardium and might improve outcomes and symptoms of patients who recently had a PCI. In this study, we aimed to assess the long-term potential benefits and safety of trimetazidine added to standard evidence-based medical treatment in patients who had a recent successful PCI.

Methods

We did a randomised, double-blind, placebo-controlled, event-driven trial of trimetazidine added to standard background therapy in patients who had undergone successful PCI at 365 centres in 27 countries across Europe, South America, Asia, and north Africa. Eligible patients were aged 21–85 years and had had either elective PCI for stable angina or urgent PCI for unstable angina or non-ST segment elevation myocardial infarction less than 30 days before randomisation. Patients were randomly assigned by an interactive web response system to oral trimetazidine 35 mg modified-release twice daily or matching placebo. Participants, study investigators, and all study staff were masked to treatment allocation. The primary efficacy endpoint was a composite of cardiac death; hospital admission for a cardiac event; recurrence or persistence of angina requiring an addition, switch, or increase of the dose of at least one antianginal drug; or recurrence or persistence of angina requiring a coronary angiography. Efficacy analyses were done according to the intention-to-treat principle. Safety was assessed in all patients who had at least one dose of study drug. This study is registered with the EU Clinical Trials Register (EudraCT 2010-022134-89).

Findings

From Sept 17, 2014, to June 15, 2016, 6007 patients were enrolled and randomly assigned to receive either trimetazidine (n=2998) or placebo (n=3009). After a median follow-up of 47·5 months (IQR 42·3–53·3), incidence of primary endpoint events was not significantly different between the trimetazidine group (700 [23·3%] patients) and the placebo group (714 [23·7%]; hazard ratio 0·98 [95% CI 0·88–1·09], p=0·73). When analysed individually, there were no significant differences in the incidence of the components of the primary endpoint between the treatment groups. Similar results were obtained when patients were categorised according to whether they had an elective or urgent PCI. 1219 (40·9%) of 2983 patients in the trimetazidine group and 1230 (41·1%) of 2990 patients in the placebo group had serious treatment-emergent adverse events. Frequencies of adverse events of interest were similar between the groups.

Interpretation

Our results show that the routine use of oral trimetazidine 35 mg twice daily over several years in patients receiving optimal medical therapy, after successful PCI, does not influence the recurrence of angina or the outcome; these findings should be taken into account when considering the place of trimetazidine in clinical practice. However, the long-term prescription of this treatment does not appear to be associated with any statistically significant safety concerns in the population studied.

DOI: 10.1016/S0140-6736(20)31790-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31790-6/fulltext