PMID- 35101369 OWN - NLM STAT- MEDLINE DCOM- 20220509 LR - 20220509 IS - 2095-4964 (Print) VI - 20 IP - 2 DP - 2022 Mar TI - Antiplatelet and myocardial protective effect of Shexiang Tongxin Dropping Pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial. PG - 126-134 LID - S2095-4964(22)00001-2 [pii] LID - 10.1016/j.joim.2022.01.001 [doi] AB - BACKGROUND: High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown. OBJECTIVE: The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated. DESIGN, PARTICIPANTS AND INTERVENTION: This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone. MAIN OUTCOME MEASURES: The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3. RESULTS: A total of 118 subjects (mean age: [66.8 +/- 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 +/- 37.3] vs. [67.8 +/- 53.1] counts/muL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% +/- 20.8% in STDP group vs. 36.0% +/- 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups. CONCLUSION: STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only. TRIAL REGISTRATION: This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785. CI - Copyright (c) 2022. Published by Elsevier B.V. FAU - Lin, Yan-Jun AU - Lin YJ AD - Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. FAU - Jiao, Kun-Li AU - Jiao KL AD - Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. FAU - Liu, Bo AU - Liu B AD - Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. FAU - Fang, Lu AU - Fang L AD - Haematopoiesis and Leukocyte Biology Laboratory, Baker Heart and Diabetes Research Institute, Melbourne, VIC 3004, Australia. FAU - Meng, Shu AU - Meng S AD - Department of Cardiology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. Electronic address: mengshu@xinhuamed.com.cn. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20220104 PL - Netherlands TA - J Integr Med JT - Journal of integrative medicine JID - 101603118 RN - 0 (Biomarkers) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Galectin 3) RN - 0 (Platelet Aggregation Inhibitors) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 0 (shexiang tongxin) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 61D2G4IYVH (Adenosine Diphosphate) RN - A74586SNO7 (Clopidogrel) RN - EC 1.14.14.1 (Cytochrome P-450 CYP2C19) SB - IM MH - Adenosine Diphosphate MH - Angina, Unstable/chemically induced MH - Animals MH - Biomarkers MH - Clopidogrel MH - Cytochrome P-450 CYP2C19/genetics MH - Drugs, Chinese Herbal MH - Galectin 3 MH - Humans MH - Intercellular Adhesion Molecule-1 MH - Male MH - Mice MH - *Percutaneous Coronary Intervention/adverse effects MH - Platelet Aggregation Inhibitors/adverse effects MH - Vascular Cell Adhesion Molecule-1/genetics OTO - NOTNLM OT - CYP2C19 gene polymorphism OT - Dual antiplatelet therapy OT - Platelet reactivity OT - Shexiang Tongxin Dropping Pill OT - Traditional Chinese medicine COIS- Declaration of competing interest The authors declare that they have no competing interest. EDAT- 2022/02/02 06:00 MHDA- 2022/05/10 06:00 CRDT- 2022/02/01 05:48 PHST- 2020/11/02 00:00 [received] PHST- 2021/12/17 00:00 [accepted] PHST- 2022/02/02 06:00 [pubmed] PHST- 2022/05/10 06:00 [medline] PHST- 2022/02/01 05:48 [entrez] AID - S2095-4964(22)00001-2 [pii] AID - 10.1016/j.joim.2022.01.001 [doi] PST - ppublish SO - J Integr Med. 2022 Mar;20(2):126-134. doi: 10.1016/j.joim.2022.01.001. Epub 2022 Jan 4.