title: Meta-Analysis of Comparison of the Newer Oral P2Y12 Inhibitors (Prasugrel or Ticagrelor) to Clopidogrel in Patients With Non-ST-Elevation Acute Coronary Syndrome.
abstract: Newer oral P2Y12 inhibitors are more potent and have faster onset of action than clopidogrel. However, the efficacy and safety in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are not well studied. A systemic search of MEDLINE and EMBASE databases was performed to identify randomized clinical trials comparing newer oral P2Y12 inhibitors (prasugrel or ticagrelor) to clopidogrel in patients with NSTE-ACS. The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), and stroke (major cardiovascular events [MACE]). Secondary outcomes were individual components of the primary outcome, all-cause mortality, and Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding. A total of 31,470 patients with NSTE-ACS from 4 randomized clinical trials were included (newer oral P2Y12 inhibitors: 15,951; clopidogrel: 15,519). Newer oral P2Y12 inhibitors significantly decreased MACE (relative risk [RR] 0.87, 95% confidence interval [CI] 0.80 to 0.95) and MI (RR 0.85, 95% CI 0.75 to 0.96) and showed a trend toward reduction of cardiovascular death (RR 0.89, 95% CI 0.71 to 1.01). There was a significant increase in TIMI major bleeding (RR 1.27, 95% CI 1.07 to 1.50) and TIMI major or minor bleeding (RR 1.20, 95% CI 1.02 to 1.42). Results were largely similar when stratified by ticagrelor versus prasugrel (pinteraction >0.05) except for increased TIMI major/minor bleeding with prasugrel than ticagrelor (pinteraction = 0.01). In conclusion, in patients with NSTE-ACS, newer oral P2Y12 inhibitors decrease MACE and MI at the expense of a significant increase in the risk of bleeding. Treatment of 1,000 patients with newer oral P2Y12 inhibitors will prevent 16 MACE and 13 MIs at the expense of increase in 6 major bleeding events.
authors.affiliation: Department of Cardiology, Mount Sinai St. Luke's and Roosevelt Hospitals, New York, New York.
authors.forename: Chirag
authors.initials: C
authors.lastname: Bavishi
authors.affiliation: Division of Cardiology, Mount Sinai Medical Center, New York, New York.
authors.forename: Sadik
authors.initials: S
authors.lastname: Panwar
authors.affiliation: Division of Cardiology, Mount Sinai Medical Center, New York, New York; Department of Cardiology, Bern University Hospital, Bern, Switzerland.
authors.forename: Franz H
authors.initials: FH
authors.lastname: Messerli
authors.affiliation: Division of Cardiology, New York University School of Medicine, New York, New York. Electronic address: sripalbangalore@gmail.com.
authors.forename: Sripal
authors.initials: S
authors.lastname: Bangalore
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000284:Administration, Oral; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006801:Humans; D010879:Piperazines / Q000008:administration & dosage*; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage; D013876:Thiophenes / Q000008:administration & dosage*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine