title: Safety and efficacy of adjusted-dose eptifibatide in patients with acute coronary syndromes and reduced renal function.
abstract: BACKGROUND
  Dose adjustment of renally excreted antithrombotic drugs is recommended for patients with reduced renal function. We examined the influence of dose modification on bleeding and efficacy.
  
  
  METHODS
  Based on initial study drug infusion rate, Early GP IIb/IIIa Inhibition in non-ST-segment elevation acute coronary syndromes (EARLY ACS) patients were categorized into groups: standard dose (2 μg/kg/min; estimated creatinine clearance [eCrCl] ≥50 ml/min), adjusted dose (1 μg/kg/min; eCrCl <50 ml/min, per protocol), excess dose (2 μg/kg/min; eCrCl <50 ml/min). We explored relationships among initial dosing, randomized treatment assignment, and bleeding and ischemic end points (96-h composite of death, myocardial infarction [MI], recurrent ischemia requiring urgent revascularization or thrombotic bailout, and 30-d death or MI).
  
  
  RESULTS
  Of 8,708 patients with eCrCl and dosing data, 19% had eCrCl <50 ml/min. Of these, 13% received adjusted dose eptifibatide and 6% received an excess dose. Across all dosing groups, no significant reductions were found in ischemic end points between early versus delayed provisional eptifibatide (OR 1.14, 95% CI 0.80-1.65; OR 1.13, 95% CI 0.81-1.56, respectively, for 96-h and 30-d composite end points). Bleeding risk was not significantly increased in the early versus delayed provisional treatment group in either the adjusted (OR 1.50, 95% CI 0.95-2.39) or excess dose group (OR 1.67, 95% CI 0.85-3.39). There were no significant interactions between dose group and treatment strategy on bleeding or efficacy.
  
  
  CONCLUSIONS
  Similar to observations in practice, despite guidelines recommendations and protocol guidance, 34% of EARLY ACS patients with reduced renal function failed to receive an appropriately adjusted study drug infusion. Use of an appropriately adjusted eptifibatide infusion was not associated with expected reductions in bleeding among patients with renal insufficiency.
authors.affiliation: Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. mello004@mc.duke.edu
authors.forename: Chiara
authors.initials: C
authors.lastname: Melloni
authors.forename: Stefan K
authors.initials: SK
authors.lastname: James
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: White
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
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 / Q000150:complications / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D003404:Creatinine / Q000378:metabolism; D003695:Delivery of Health Care; D054796:Drug Dosage Calculations; D000077542:Eptifibatide; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D007677:Kidney Function Tests / Q000706:statistics & numerical data*; D008297:Male; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D017410:Practice Guidelines as Topic; D051437:Renal Insufficiency / Q000150:complications* / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D003404:Creatinine; D000077542:Eptifibatide