title: Upstream clopidogrel use and the efficacy and safety of early eptifibatide treatment in patients with acute coronary syndrome: an analysis from the Early Glycoprotein IIb/IIIa Inhibition in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial.
abstract: BACKGROUND
  In the Early Glycoprotein IIb/IIIa Inhibition in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial, routine preangiography eptifibatide use was not superior to delayed provisional use but led to more bleeding. This analysis examines efficacy and safety of early eptifibatide in the setting of concurrent upstream clopidogrel use.
  
  
  RESULTS
  In EARLY-ACS, clopidogrel use and timing were determined by treating physicians, but randomization to early eptifibatide versus placebo was stratified by the intent to use upstream clopidogrel. Among 9166 non-ST-elevation acute coronary syndrome patients who underwent coronary angiography, intent to use upstream clopidogrel was declared in 6895 (75%), and 7068 (77%) received upstream clopidogrel. After multivariable adjustment, intended upstream clopidogrel use did not differentially influence the effect of early eptifibatide on the primary end point of 96-hour death/myocardial infarction/recurrent ischemia requiring urgent revascularization/thrombotic bailout (interaction P=0.988). Early eptifibatide use reduced 30-day death/myocardial infarction among patients with intended upstream clopidogrel (adjusted odds ratio 0.85; 95% confidence interval 0.73 to 0.99) but not among those without intended upstream clopidogrel use (adjusted odds ratio 1.02; 95% confidence interval 0.80 to 1.30). However, the clopidogrel by randomized treatment interaction term was not significant (P=0.23). Thrombolysis in Myocardial Infarction major bleeding risk was increased with early eptifibatide in the setting of upstream clopidogrel use. Results were similar using actual clopidogrel treatment strata.
  
  
  CONCLUSIONS
  Routine early eptifibatide use, compared with delayed provisional use, may be associated with lower 30-day ischemic risk in non-ST-elevation acute coronary syndrome patients also treated with clopidogrel before angiography. The benefit-risk ratio of intensive platelet inhibition with combined early use of antiplatelet agents needs further evaluation in prospective randomized trials.
authors.affiliation: Duke Clinical Research Institute, 2400 Pratt St., Durham, NC 27705, USA. tracy.wang@duke.edu
authors.forename: Tracy Y
authors.initials: TY
authors.lastname: Wang
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: White
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.forename: Uwe
authors.initials: U
authors.lastname: Zeymer
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Stefan K
authors.initials: SK
authors.lastname: James
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: L Kristin
authors.initials: LK
authors.lastname: Newby
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D000077144:Clopidogrel; D017023:Coronary Angiography; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D000077542:Eptifibatide; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077144:Clopidogrel; D000077542:Eptifibatide; D013988:Ticlopidine