State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Departments of Neurology and Population and Data Science, University of Texas Southwestern Medical Center, Dallas.
JAMA. 2023 Oct 24;330(16):1534-1545. doi: 10.1001/jama.2023.19524.
Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials.
To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI).
DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021.
Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments.
The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year.
Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], -1.8% [95% CI, -3.2% to -0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, -1.2% [95% CI, -2.5% to -0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, -3.0% [95% CI, -4.6% to -1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, -1.6% [95% CI, -3.1% to -0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms.
In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI.
ClinicalTrials.gov Identifier: NCT03792035.
通心络是一种中药复方，在体外、动物和人体小样本研究中对心肌梗死有一定疗效，但尚未在大规模随机临床试验中得到严格评估。
研究通心络是否能改善 ST 段抬高型心肌梗死（STEMI）患者的临床结局。
设计、地点和参与者：这是一项在中国 124 家医院进行的随机、双盲、安慰剂对照临床试验，纳入 STEMI 发病后 24 小时内的患者。患者于 2019 年 5 月至 2020 年 12 月入组，最后一次随访日期为 2021 年 12 月 15 日。
患者随机 1:1 接受通心络或安慰剂口服治疗 12 个月（随机后立即给予负荷剂量 2.08 g，随后维持剂量 1.04 g，每日 3 次），此外还接受 STEMI 指南指导的治疗。
主要终点是 30 天内主要不良心脑血管事件（MACCEs），包括心脏死亡、心肌再梗死、紧急冠状动脉血运重建和卒中。MACCEs 的随访时间为每 3 个月至 1 年。
在 3797 名随机患者中，3777 名（通心络组 1889 名，安慰剂组 1888 名；平均年龄 61 岁，76.9%为男性）被纳入主要分析。通心络组 30 天内发生 MACCEs 的患者有 64 例（3.4%），安慰剂组发生 99 例（5.2%）（相对风险 [RR]，0.64 [95% CI，0.47 至 0.88]；风险差异 [RD]，-1.8% [95% CI，-3.2% 至 -0.6%]）。30 天 MACCEs 的各组成部分，包括心脏死亡（56 例 [3.0%] vs 80 例 [4.2%]；RR，0.70 [95% CI，0.50 至 0.99]；RD，-1.2% [95% CI，-2.5% 至 -0.1%]）也明显低于安慰剂组。到 1 年时，通心络组的 MACCEs 发生率仍较低（100 例 [5.3%] vs 157 例 [8.3%]；HR，0.64 [95% CI，0.49 至 0.82]；RD，-3.0% [95% CI，-4.6% 至 -1.4%]）和心脏死亡（85 例 [4.5%] vs 116 例 [6.1%]；HR，0.73 [95% CI，0.55 至 0.97]；RD，-1.6% [95% CI，-3.1% 至 -0.2%]）。其他次要终点，包括 30 天卒中、30 天和 1 年大出血、1 年全因死亡率和支架内血栓形成（<24 小时；1-30 天；1-12 个月），两组间无显著差异。通心络组的药物不良反应发生率高于安慰剂组（40 例 [2.1%] vs 21 例 [1.1%]；P = .02），主要由胃肠道症状引起。
在 STEMI 患者中，中药通心络作为 STEMI 指南指导治疗的辅助治疗，显著改善了 30 天和 1 年的临床结局。还需要进一步研究来确定通心络在 STEMI 中的作用机制。
ClinicalTrials.gov 标识符：NCT03792035。
