title: Safety and efficacy of IIb/IIIa inhibitors in combination with highly active oral antiplatelet regimens in acute coronary syndromes: A meta-analysis of pivotal trials.
abstract: The risk and benefit of GP-IIb/IIIa Inhibition (GPI) in combination with recent antiplatelet regimens in acute coronary syndromes (ACS) remain unassessed. The advent of fast-acting highly active oral P2Y12inhibitors questions the additional value and risk of their association with GPI. We studied the effect of GPI in combination with prasugrel and ticagrelor, compared to clopidogrel on major bleeding in pivotal randomized controlled trials in the setting of ACS, using a meta-analytic approach. A similar analysis, further including the comparison of a double versus standard dose clopidogrel regimen, was performed for the risk of the primary efficacy endpoint. The combination of GPI and recent P2Y12inhibitors was associated with a similar risk of bleeding as compared with GPI and the standard clopidogrel regimen (RR 0.92 [0.74; 1.13]). The benefit of recent regimens, including double dose clopidogrel, in reducing the primary ischemic endpoint (RR 0.86 [0.78; 0.94]) persisted in those treated with GPI. Although GPI use was associated with a consistent increase in the risk of bleeding in both recent (RR 1.27 [1.05-1.55]) and standard regimens (RR 2.01 [1.64-2.47]), the relative magnitude of such an increase was lower in association with prasugrel or ticagrelor as compared with clopidogrel. The risk of bleeding using a combination of GPI and oral antiplatelet regimens is mainly related to the use of GPI and not the oral antiplatelet regimen. Considering the absence of increased risk of bleeding and the persistence of the benefit of recent P2Y12regimens in combination with GPI as compared with the standard clopidogrel regimen, the use of such a combination within the guidelines is supported by our findings.
authors.affiliation: a Department of Cardiology , Caen University Hospital , Caen , France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Roule
authors.affiliation: a Department of Cardiology , Caen University Hospital , Caen , France.
authors.forename: Moaad
authors.initials: M
authors.lastname: Agueznai
authors.affiliation: a Department of Cardiology , Caen University Hospital , Caen , France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Sabatier
authors.affiliation: a Department of Cardiology , Caen University Hospital , Caen , France.
authors.forename: Katrien
authors.initials: K
authors.lastname: Blanchart
authors.affiliation: a Department of Cardiology , Caen University Hospital , Caen , France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Lemaître
authors.affiliation: a Department of Cardiology , Caen University Hospital , Caen , France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ardouin
authors.affiliation: b ACTION Academic Group , Institut de Cardiologie, Pitié-Salpétrière University Hospital , Paris , France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Collet
authors.affiliation: a Department of Cardiology , Caen University Hospital , Caen , France.
authors.forename: Paul
authors.initials: P
authors.lastname: Milliez
authors.affiliation: b ACTION Academic Group , Institut de Cardiologie, Pitié-Salpétrière University Hospital , Paris , France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.affiliation: a Department of Cardiology , Caen University Hospital , Caen , France.|b ACTION Academic Group , Institut de Cardiologie, Pitié-Salpétrière University Hospital , Paris , France.
authors.forename: Farzin
authors.initials: F
authors.lastname: Beygui
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002986:Clinical Trials as Topic; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D015897:Comorbidity; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D000068799:Prasugrel Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Acute coronary syndrome; clopidogrel; glycoprotein IIb/IIIa inhibitor; prasugrel; ticagrelor