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

Xiao-Fang Tang; Jing-Yao Fan; Jing Meng; Chen Jin; Jin-Qing Yuan; Yue-Jin Yang

doi:10.1016/j.atherosclerosis.2014.01.017

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

Atherosclerosis. 2014 Apr;233(2):568-578. doi: 10.1016/j.atherosclerosis.2014.01.017. Epub 2014 Jan 21.

Authors

Xiao-Fang Tang¹, Jing-Yao Fan¹, Jing Meng², Chen Jin³, Jin-Qing Yuan⁴, Yue-Jin Yang⁵

Affiliations

¹ 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.
² Nursing School, Beijing University of Chinese Medicine, Beijing 100102, China.
³ 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.
⁴ 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.
⁵ 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.

PMID: 24534451
DOI: 10.1016/j.atherosclerosis.2014.01.017

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.

Methods and 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.

Keywords: Antiplatelet therapy; Coronary artery disease; Meta-analysis; P2Y12 inhibitors.

Publication types

Comparative Study
Meta-Analysis
Research Support, Non-U.S. Gov't
Review

MeSH terms

Acute Coronary Syndrome / epidemiology
Acute Coronary Syndrome / etiology
Acute Coronary Syndrome / prevention & control
Adenosine / administration & dosage
Adenosine / adverse effects
Adenosine / analogs & derivatives
Adenosine / therapeutic use
Adenosine Monophosphate / administration & dosage
Adenosine Monophosphate / adverse effects
Adenosine Monophosphate / analogs & derivatives
Adenosine Monophosphate / therapeutic use
Administration, Oral
Clopidogrel
Coronary Artery Disease / complications
Coronary Artery Disease / drug therapy*
Coronary Restenosis / prevention & control
Fibrinolytic Agents / adverse effects
Hemorrhage / chemically induced
Hemorrhage / prevention & control
Humans
Injections, Intravenous
Multicenter Studies as Topic / statistics & numerical data
Myocardial Infarction / epidemiology
Myocardial Infarction / etiology
Myocardial Infarction / prevention & control*
Myocardial Infarction / therapy
Piperazines / administration & dosage
Piperazines / adverse effects
Piperazines / therapeutic use
Prasugrel Hydrochloride
Purinergic P2Y Receptor Antagonists / administration & dosage
Purinergic P2Y Receptor Antagonists / adverse effects
Purinergic P2Y Receptor Antagonists / therapeutic use*
Quinazolinones / administration & dosage
Quinazolinones / adverse effects
Quinazolinones / therapeutic use
Randomized Controlled Trials as Topic / statistics & numerical data
Stents
Stroke / epidemiology
Stroke / prevention & control
Sulfonamides / administration & dosage
Sulfonamides / adverse effects
Sulfonamides / therapeutic use
Thiophenes / administration & dosage
Thiophenes / adverse effects
Thiophenes / therapeutic use
Thrombolytic Therapy / adverse effects
Ticagrelor
Ticlopidine / adverse effects
Ticlopidine / analogs & derivatives*
Ticlopidine / therapeutic use

Substances

Fibrinolytic Agents
Piperazines
Purinergic P2Y Receptor Antagonists
Quinazolinones
Sulfonamides
Thiophenes
Adenosine Monophosphate
cangrelor
elinogrel
Clopidogrel
Prasugrel Hydrochloride
Ticagrelor
Adenosine
Ticlopidine