PMID- 35438151
OWN - NLM
STAT- MEDLINE
DCOM- 20221205
LR  - 20221228
IS  - 2055-6845 (Electronic)
VI  - 8
IP  - 8
DP  - 2022 Dec 2
TI  - Antiplatelet effect, safety, and pharmacokinetics of vicagrel in patients with 
      coronary artery disease undergoing percutaneous coronary intervention.
PG  - 806-814
LID - 10.1093/ehjcvp/pvac026 [doi]
AB  - AIMS: Vicagrel, a novel antiplatelet prodrug to overcome the residual high 
      platelet reactivity of clopidogrel induced by inactive metabolism and cytochrome 
      P450 (CYP) 2C19 polymorphisms, provides favourable antiplatelet inhibition in 
      healthy volunteers. However, its antiplatelet effect and safety in patients with 
      coronary artery disease (CAD) are unclear. METHODS AND RESULTS: This was a 
      multicentre, randomized, double-blind, triple-dummy, dose-exploring phase II 
      trial comparing the antiplatelet activity and safety of vicagrel at different 
      doses vs. those of clopidogrel in patients with CAD undergoing percutaneous 
      coronary intervention (PCI). The primary endpoint was inhibition of adenosine 
      diphosphate (ADP)-induced platelet aggregation (%IPA) after loading and 
      maintenance doses (LD/MD) at 28 days. Safety endpoints included adverse events 
      (AEs) and Bleeding Academic Research Consortium-defined any bleeding. 
      Pharmacokinetic (PK) profiles and the influence of CYP2C19 polymorphisms were 
      explored in subgroup analysis. Two hundred and seventy-nine patients diagnosed 
      with stable CAD (51.97%), unstable angina (40.86%), and myocardial infarction 
      (7.17%) were randomized to receive vicagrel 20/5 mg (LD/MD), 24/6 mg, or 
      30/7.5 mg or clopidogrel 300/75 mg in combination with aspirin. %IPAs on Day 28 
      were 30.19%, 35.02%, 45.61%, and 32.55% for vicagrel 20/5, 24/6, and 30/7.5 mg 
      and clopidogrel, respectively, and were comparable across all groups 
      (P = 0.0694). The plasma concentration of the vicagrel active metabolite M15-2 
      had a similar area under curve and Tmax to those of clopidogrel. There were no 
      significant differences in AEs (4.35%, 0%, 1.45%, and 5.56% for vicagrel 20/5, 
      24/6, and 30/7.5 mg and clopidogrel, P = 0.6667) or any bleeding (13.04%, 14.06%, 
      11.59%, and 11.11% for vicagrel 20/5, 24/6, and 30/7.5 mg and clopidogrel, 
      respectively, P = 0.95) across four groups. %IPAs and PK profiles of vicagrel did 
      not vary significantly among different CYP2C19 metabolizers. CONCLUSION: Vicagrel 
      had comparable antiplatelet effect and safety to clopidogrel in patients with CAD 
      undergoing PCI.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the 
      European Society of Cardiology.
FAU - Zhao, Xin
AU  - Zhao X
AD  - Department of Cardiology, General Hospital of Northern Theater Command, No. 83 
      Wenhua Road, Shenhe District, Shenyang 110016, Liaoning, China.
FAU - Ma, Sicong
AU  - Ma S
AD  - Department of Cardiology, General Hospital of Northern Theater Command, No. 83 
      Wenhua Road, Shenhe District, Shenyang 110016, Liaoning, China.
AD  - Department of Cardiology, the Second Hospital of Jilin University, Changchun, 
      Jilin, China.
FAU - Kang, Yi
AU  - Kang Y
AD  - Department of Heart Center, First Hospital of Tsinghua University, Beijing, 
      China.
FAU - Tang, Chengchun
AU  - Tang C
AD  - Department of Cardiology, Zhongda Hospital Southeast University, Nanjing, 
      Jiangsu, China.
FAU - Liu, Bin
AU  - Liu B
AD  - Department of Cardiology, the Second Hospital of Jilin University, Changchun, 
      Jilin, China.
FAU - Jiang, Hong
AU  - Jiang H
AD  - Department of Cardiology, China-Japan Friendship Hospital, Beijing, China.
FAU - Zheng, Mingqi
AU  - Zheng M
AD  - Department of Cardiology, the First Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China.
FAU - Tang, Yu
AU  - Tang Y
AD  - Department of Cardiology, Jiangxi Provincial People's Hospital, Nanchang, 
      Jiangxi, China.
FAU - Sun, Hongbin
AU  - Sun H
AD  - State Key Laboratory of Natural Medicines and Center of Drug Discovery, College 
      of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
FAU - Liu, Yongqiang
AU  - Liu Y
AD  - R&D Department, Jiangsu Vcare PharmaTech Co., Ltd, Nanjing, Jiangsu, China.
FAU - Lai, Xiaojuan
AU  - Lai X
AD  - R&D Department, Jiangsu Vcare PharmaTech Co., Ltd, Nanjing, Jiangsu, China.
FAU - Gong, Yanchun
AU  - Gong Y
AD  - R&D Department, Jiangsu Vcare PharmaTech Co., Ltd, Nanjing, Jiangsu, China.
FAU - Li, Yongguo
AU  - Li Y
AD  - R&D Department, Guangzhou JOYO Pharma Ltd, Guangzhou, Guangdong, China.
FAU - Qi, Zizhao
AU  - Qi Z
AD  - Department of Cardiology, General Hospital of Northern Theater Command, No. 83 
      Wenhua Road, Shenhe District, Shenyang 110016, Liaoning, China.
FAU - Ren, Ling
AU  - Ren L
AD  - Department of Cardiology, General Hospital of Northern Theater Command, No. 83 
      Wenhua Road, Shenhe District, Shenyang 110016, Liaoning, China.
FAU - Li, Jing
AU  - Li J
AD  - Department of Cardiology, General Hospital of Northern Theater Command, No. 83 
      Wenhua Road, Shenhe District, Shenyang 110016, Liaoning, China.
FAU - Li, Yi
AU  - Li Y
AD  - Department of Cardiology, General Hospital of Northern Theater Command, No. 83 
      Wenhua Road, Shenhe District, Shenyang 110016, Liaoning, China.
FAU - Han, Yaling
AU  - Han Y
AUID- ORCID: 0000-0003-4569-6737
AD  - Department of Cardiology, General Hospital of Northern Theater Command, No. 83 
      Wenhua Road, Shenhe District, Shenyang 110016, Liaoning, China.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur Heart J Cardiovasc Pharmacother
JT  - European heart journal. Cardiovascular pharmacotherapy
JID - 101669491
RN  - A74586SNO7 (Clopidogrel)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
RN  - 0 (methyl 
      2-(2-acetoxy-6,7-dihydrothieno(3,2-c)pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate)
RN  - 0 (Platelet Aggregation Inhibitors)
SB  - IM
MH  - Humans
MH  - Clopidogrel/adverse effects
MH  - Cytochrome P-450 CYP2C19/genetics
MH  - *Percutaneous Coronary Intervention/adverse effects
MH  - *Coronary Artery Disease/diagnosis/therapy
MH  - Platelet Aggregation Inhibitors/adverse effects
MH  - Hemorrhage/chemically induced
OTO - NOTNLM
OT  - Clopidogrel
OT  - Coronary artery disease
OT  - Percutaneous coronary intervention
OT  - Vicagrel
EDAT- 2022/04/20 06:00
MHDA- 2022/12/06 06:00
CRDT- 2022/04/19 08:40
PHST- 2022/01/23 00:00 [received]
PHST- 2022/03/13 00:00 [revised]
PHST- 2022/04/17 00:00 [accepted]
PHST- 2022/04/20 06:00 [pubmed]
PHST- 2022/12/06 06:00 [medline]
PHST- 2022/04/19 08:40 [entrez]
AID - 6570569 [pii]
AID - 10.1093/ehjcvp/pvac026 [doi]
PST - ppublish
SO  - Eur Heart J Cardiovasc Pharmacother. 2022 Dec 2;8(8):806-814. doi: 
      10.1093/ehjcvp/pvac026.