Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, 16 Nanxiaojie, Inner Dongzhimen, Beijing 100700, China.
XiYuan Hospital, China Academy of Chinese Medical Sciences, No.1 Xiyuan playground Road, Haidian District, Beijing 100091, China.
Phytomedicine. 2021 Jan;81:153419. doi: 10.1016/j.phymed.2020.153419. Epub 2020 Dec 10.
Salvia Miltiorrhiza Depside Salt (SMDS) was extracted from Salvia miltiorrhiza with high-quality control of active principles. In 2005, China's FDA approved the use of SMDS for stable angina pectoris (SAP), but the evidence of SMDS combined with aspirin remains unclear.
The aim of this study was to assess the clinical effectiveness and safety of SMDS combined with aspirin in patients with SAP.
A multicenter, pragmatic, three-armed parallel group and an individually randomized controlled superiority trial was designed. Participants aged 35 to 75 years old with SAP were recruited from four "Class Ⅲ Grade A" hospitals in China. Participants who were randomized into the SMDS group were treated with SMDS by intravenous drip. Participants in the control group received aspirin enteric-coated tablets (aspirin). Participants who were randomly assigned to the combination group received SMDS combined with aspirin. All participants received standard care from clinicians, without any restrictions. The primary outcome measure was thromboelastography (TEG). Secondary outcome measures included symptom score of the Seattle Angina Questionnaire (SAQ), visual analogue scale (VAS) score of traditional Chinese medicine (TCM) symptoms, platelet aggregation measured by light transmittance aggregometry (LTA), and fasting blood glucose. Effectiveness evaluation data were collected at baseline and ten days after treatment. Researchers followed up with participants for one month after treatment to determine whether adverse events (AEs) or adverse drug reactions (ADRs) such as bleeding tendency occurred. All statistical calculations were carried out with R 3.5.3 statistical analysis software.
A total of 135 participants completed follow-up data on the primary outcome after ten days of treatment. Participants in the SMDS combined aspirin group had the highest improvement rate of sensitivity in AA% [p < 0.001, 95% CI (0.00-0.00)], from 30.6% before treatment to 81.6% after treatment. Participants with drug resistance (AA% < 20%) in the SMDS combined with aspirin group also had the highest sensitivity rate [p < 0.001, 95% CI (0.00-0.00)] after treatment (accounting for 81.0% of the combination group and 60.7% of the sensitive participants). The improvement of TCM symptoms in participants treated with SMDS combined with aspirin was significantly better than that of the aspirin group [MD = 1.71, 95% CI (0.15-3.27), p = 0.032]. There were no significant differences in other indexes (R, TPI, MA, K, CI, α value) of TEG, SAQ, platelet aggregation and fasting blood glucose among the three groups. No bleeding tendency or ADRs occurred in all participants.
SMDS combined with aspirin is a clinically effective and safe intervention to treat adults aged 35 and older with SAP. This trial shows that SMDS combined with aspirin can significantly improve the sensitivity rate of AA% in TEG and the VAS score of TCM symptoms. Further large samples and high-quality research are needed to determine if certain participants might benefit more from SMDS combined with aspirin. The study protocol was registered in the Clinical Trials USA registry (registration No. NCT02694848).
丹参多酚酸盐（SMDS）是从丹参中提取的高质量控制有效成分的药物。2005 年，中国食品药品监督管理局批准 SMDS 用于稳定型心绞痛（SAP），但 SMDS 联合阿司匹林的疗效证据尚不清楚。
本研究旨在评估 SMDS 联合阿司匹林治疗 SAP 患者的临床疗效和安全性。
采用多中心、实用、三臂平行组和个体随机对照优效性试验设计。从中国四家“三级甲等”医院招募年龄在 35 至 75 岁之间的 SAP 患者。随机分配到 SMDS 组的参与者接受 SMDS 静脉滴注治疗。对照组服用阿司匹林肠溶片（阿司匹林）。随机分配到联合组的参与者接受 SMDS 联合阿司匹林治疗。所有参与者均接受临床医生的标准护理，不受任何限制。主要结局测量指标为血栓弹力图（TEG）。次要结局测量指标包括西雅图心绞痛问卷（SAQ）症状评分、中医（TCM）症状视觉模拟量表（VAS）评分、光透射聚集法（LTA）测量的血小板聚集率和空腹血糖。在治疗前和治疗后十天收集有效性评估数据。研究人员在治疗后一个月对参与者进行随访，以确定是否发生出血倾向等不良事件（AE）或不良药物反应（ADR）。所有统计计算均使用 R 3.5.3 统计分析软件进行。
共有 135 名参与者在治疗十天后完成了主要结局的随访数据。在 SMDS 联合阿司匹林组中，AA%的敏感性改善率最高[P<0.001，95%置信区间（0.00-0.00）]，从治疗前的 30.6%提高到治疗后的 81.6%。SMDS 联合阿司匹林组中药物抵抗（AA%<20%）的患者治疗后敏感性也最高[P<0.001，95%置信区间（0.00-0.00）]，占联合组的 81.0%，敏感患者的 60.7%。SMDS 联合阿司匹林治疗组 TCM 症状的改善明显优于阿司匹林组[MD=1.71，95%置信区间（0.15-3.27），P=0.032]。三组 TEG、SAQ、血小板聚集率和空腹血糖的其他指标（R、TPI、MA、K、CI、α 值）均无显著差异。所有参与者均未出现出血倾向或 ADR。
SMDS 联合阿司匹林是治疗 35 岁及以上 SAP 成人的一种临床有效且安全的干预措施。本研究表明，SMDS 联合阿司匹林可显著提高 TEG 中 AA%的敏感性率和 TCM 症状的 VAS 评分。需要进一步的大样本和高质量研究来确定某些参与者是否可能从 SMDS 联合阿司匹林中获益更多。该研究方案已在 ClinicalTrials.gov 注册（注册号：NCT02694848）。
