Background:High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2 C19,the enzyme that converts clopidogrel into its active form.Shexiang Tongxin Dropping Pill(STDP)is ...Background:High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2 C19,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 CYP2 C19 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(hs Tn I);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.CYP2 C19 genotype distribution was comparable between the 2 groups.In comparison to the control group,the STDP group had significantly lower CKMB(P<0.05)but similar hs Tn I(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/μL 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.展开更多
基金supported by Science and Technology Commission of Shanghai Municipality(Grant No.16401972000)Shanghai Municipal Administration of Traditional Chinese Medicine(Grant No.ZY(2018-2020)-FWTX-3027)。
文摘Background:High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2 C19,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 CYP2 C19 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(hs Tn I);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.CYP2 C19 genotype distribution was comparable between the 2 groups.In comparison to the control group,the STDP group had significantly lower CKMB(P<0.05)but similar hs Tn I(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/μL 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.
