title: Impact of new oral or intravenous P2Y12 inhibitors and clopidogrel on major ischemic and bleeding events in patients with coronary artery disease: a meta-analysis of randomized trials.
abstract: OBJECTIVE
  New P2Y12 inhibitors can be classified as oral (prasugrel and ticagrelor) and intravenous drugs (cangrelor and elinogrel). These P2Y12 inhibitors might be superior to clopidogrel for reducing ischemic events in patients with coronary artery disease (CAD). We performed a meta-analysis of randomized trials that compared new oral or intravenous P2Y12 inhibitors with clopidogrel to determine their efficacy and safety in patients.
  
  
  RESULTS
  Twelve randomized, placebo-controlled studies and two subgroup analyses of included studies on ST-segment elevation myocardial infarction (STEMI) were included. The database consisted of 82,784 patients, with 43,875 (53%) on new oral P2Y12 inhibitors and 38909 (47%) on intravenous P2Y12 inhibitors compared with clopidogrel. The primary efficacy endpoint was major adverse cardiac events (MACEs). The primary safety endpoint was thrombolysis in myocardial infarction (TIMI) major bleeding. New oral P2Y12 inhibitors significantly decreased MACEs (odds ratio: 0.85, p<0.0001 for the whole cohort; OR: 0.77, p=0.04 for STEMI) and all-cause death (OR: 0.88, p=0.04 for the whole cohort; OR: 0.77, p=0.01 for STEMI). Among new intravenous P2Y12 inhibitors, only cangrelor significantly decreased the risk of MACEs. An increase in TIMI major bleeding was observed only by prasugrel among the new P2Y12 inhibitors.
  
  
  CONCLUSIONS
  New oral P2Y12 inhibitors reduce ischemic events, but there is no obvious increase in major bleeding in patients with CAD, and the risk/benefit ratio is particularly favorable for STEMI patients. Moreover, only cangrelor is beneficial for ischemic events in patients on new intravenous P2Y12 inhibitors.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Jing-Yao
authors.initials: JY
authors.lastname: Fan
authors.affiliation: Nursing School, Beijing University of Chinese Medicine, Beijing 100102, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. Electronic address: dr_jinqingyuan@126.com.
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. Electronic address: dr_yuejinyang@126.com.
authors.forename: Yue-Jin
authors.initials: YJ
authors.lastname: Yang
mesh_terms: D054058:Acute Coronary Syndrome / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000249:Adenosine Monophosphate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000284:Administration, Oral; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy*; D023903:Coronary Restenosis / Q000517:prevention & control; D005343:Fibrinolytic Agents / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007275:Injections, Intravenous; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D052999:Quinazolinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D015607:Stents; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015912:Thrombolytic Therapy / Q000009:adverse effects; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D005343:Fibrinolytic Agents; D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D052999:Quinazolinones; D013449:Sulfonamides; D013876:Thiophenes; D000249:Adenosine Monophosphate; C117446:cangrelor; C549473:elinogrel; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Antiplatelet therapy; Coronary artery disease; Meta-analysis; P2Y12 inhibitors