Assessment of Eptifibatide Dosing in Renal Impairment Before and After In-Service Education Provided by Pharmacists

BACKGROUND: Anticoagulant and antithrombotic agents are frequently cited as sources of medication errors. Several factors increase the risk of receiving excess dosing of glycoprotein IIb/IIIa inhibitors in the management of acute coronary syndrome (ACS), including older age, female gender, elevated serum creatinine, a history of diabetes mellitus, and a history of heart failure. In June 2003, the manufacturer of eptifibatide released a recommendation adjusting infusion rate downward to 1 mcg per kg per minute for eptifibatide in patients with renal impairment, defined as an estimated creatinine clearance (CrCl) less than 50 ml per minute. Eptifibatide is known to accumulate in patients with renal impairment, thereby increasing hemorrhagic risk. OBJECTIVES: To assess the impact of education on physician adherence to the renal dosing recommendation for eptifibatide at 2 academic medical centers. The primary outcome measure was the proportion of patients with renal impairment dosed appropriately with eptifibatide before and after in-service education provided by a clinical pharmacist. Secondary outcome measures included the difference in the improvement in dosing adherence between the 2 sites and the influence of patient variables on the incidence of bleeding events. METHODS: This prospective study was conducted in patients with renal impairment who received eptifibatide for the medical management of unstable angina (UA) or non ST-elevation myocardial infarction (NSTEMI) or for the interventional management of chronic stable angina, UA, NSTEMI, or ST-elevation myocardial infarction (STEMI, not a Food and Drug Administration-approved use). Patient data were assessed at 2 tertiary care teaching institutions between June 2003 and December 2005. The preeducation phase for the sites ran from June 2003 through April 2005 for Site A and from June 2003 through May 2005 for Site B. The posteducation phase ran from May 2005 through December 2005 for Site A and from June 2005 through December 2005 for Site B. At site A, a 1-hour educational seminar on ACS management strategies was employed, in which 5 minutes focused on adherence of prescribers to the guideline for renal dosing recommendations for eptifibatide. This tutorial was accomplished through (1) an in-service provided by 1 clinical pharmacist to the cardiology department, and (2) handouts containing the renal dosing recommendations for eptifibatide along with dosing for other medications used to manage ACS. The intervention at Site B involved an eptifibatide-focused seminar presented to cardiologists by a clinical pharmacist, 10 minutes of which was devoted to renal dosing recommendations that included (1) a summary of literature supporting the infusion rate reduction in patients with renal impairment and (2) the specific updated dosing recommendation for eptifibatide. The data collected in retrospective chart review included patient demographics, baseline laboratory values, and risk factors for bleeding. An appropriate eptifibatide dose was defined as a physician order for a continuous infusion of 1 mcg per kg per minute in patients with an estimated CrCl less than 50 ml per minute. RESULTS: A total of 148 patients with renal impairment who received eptifibatide were evaluated (106 in the preeducation phase and 42 in the posteducation phase). A significant increase in the adherence rate for eptifibatide dosing in patients with renal impairment was observed from 36.8% in the preeducation phase to 69.0% in the posteducation phase (P less than 0.001) for the 2 sites combined. The incidence of major and minor bleeding was 16.7% in the preeducation phase and 14.3% in the posteducation phase (P=0.742). When bleeding incidence was stratified by the appropriateness of infusion, the incidence of major and minor bleeding was also similar for appropriate dosing (1 mcg per kg per minute, 16.4%) versus inappropriate dosing (2 mcg per kg per minute, 15.7%.