title: Upstream use of small-molecule glycoprotein iib/iiia inhibitors in patients with non-ST-segment elevation acute coronary syndromes: a systematic overview of randomized clinical trials.
abstract: BACKGROUND
  The use of upstream small-molecule glycoprotein (GP) IIb/IIIa inhibitors in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been studied in multiple randomized clinical trials. We systematically reviewed the effect of upstream GP IIb/IIIa inhibitor use in NSTE ACS as reported in published clinical trials.
  
  
  RESULTS
  Randomized clinical trials of upstream small-molecule GP IIb/IIIa inhibitors in NSTE ACS were identified through a PubMed and EMBASE search and were included if they contained 30-day outcome data. Odds ratios were generated from the published data and pooled by means of random effects modeling. The primary outcome measures were 30-day death and 30-day death or myocardial infarction. Primary safety measures were major bleeding and transfusion during the index hospitalization. Twelve clinical trials were included, evaluating tirofiban, eptifibatide, and lamifiban. Of these, 7 evaluated upstream GP IIb/IIIa inhibitors versus placebo (n=24 031) and 5 evaluated a strategy of upstream GP IIb/IIIa inhibitors versus upstream placebo with later provisional use at the time of percutaneous coronary intervention (n=19 643). Overall, upstream GP IIb/IIIa inhibitor use was associated with an 11% reduction in 30-day death/myocardial infarction (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.83 to 0.95) but no significant mortality effect (OR, 0.93; 95% CI, 0.83 to 1.05). The risk of major bleeding was 23% higher in patients treated with upstream GP IIb/IIIa inhibitors (OR, 1.23; 95% CI, 1.02 to 1.48). Results were similar when only trials comparing upstream GP IIb/IIIa inhibitors versus placebo were considered: 30-day death/myocardial infarction (OR, 0.88; 95% CI, 0.81 to 0.95); 30-day death (OR, 0.89; 95% CI, 0.76 to 1.03); and major bleeding (OR, 1.17; 95% CI, 0.88 to 1.54). Upstream versus selective use at percutaneous coronary intervention trended toward lower 30-day death/myocardial infarction (OR, 0.91; 95% CI, 0.82 to 1.01) but had no effect on mortality (OR, 1.00; 95% CI, 0.81 to 1.23) and increased major bleeding risk by 34% (OR, 1.34; 95% CI, 1.10 to 1.63).
  
  
  CONCLUSIONS
  In NSTE ACS, treatment with upstream small-molecule GP IIb/IIIa inhibitors provides a significant but modest ischemic benefit when compared with initial placebo. Compared with delayed, selective use at percutaneous coronary intervention, early upstream use is associated with a trend toward fewer ischemic events. However, these modest benefits are associated with an increased risk of bleeding.
authors.affiliation: Duke Clinical Research Institute, Durham, NC 27715, USA. pierluigi.tricoci@duke.edu
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.forename: L Kristin
authors.initials: LK
authors.lastname: Newby
authors.forename: Vic
authors.initials: V
authors.lastname: Hasselblad
authors.forename: David F
authors.initials: DF
authors.lastname: Kong
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: Pierre
authors.initials: P
authors.lastname: Théroux
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.forename: David J
authors.initials: DJ
authors.lastname: Moliterno
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.forename: Saman
authors.initials: S
authors.lastname: Rasoul
authors.forename: Leonardo
authors.initials: L
authors.lastname: Bolognese
authors.forename: Eric
authors.initials: E
authors.lastname: Durand
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
mesh_terms: D000085:Acetates / Q000008:administration & dosage / Q000009:adverse effects; D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology / Q000601:surgery; D000279:Administration, Cutaneous; D017130:Angioplasty; D004562:Electrocardiography; D000077542:Eptifibatide; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011183:Postoperative Complications / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D016019:Survival Analysis; D000077466:Tirofiban; D014443:Tyrosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D000085:Acetates; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; C084062:lamifiban; D000077466:Tirofiban; D000077542:Eptifibatide