A Matched Comparison of Eptifibatide Plus rt-PA Versus rt-PA Alone in Acute Ischemic Stroke

• Published in: Journal of stroke and cerebrovascular diseases 2014-05, Vol.23 (5), p.e313-e315
• Main Authors: Adeoye, Opeolu, MD, MS, Knight, William A., MD, Khoury, Jane, PhD, Schmit, Pamela A., RN, BSN, Sucharew, Heidi, PhD, Broderick, Joseph P., MD, Pancioli, Arthur M., MD
• Format: Article
• Language: English
• Subjects: Aged; Brain Ischemia - diagnosis; Brain Ischemia - drug therapy; Cardiovascular; clinical trial; Disability Evaluation; Double-Blind Method; Drug Therapy, Combination; eptifibatide; Female; Fibrinolytic Agents - administration & dosage; Fibrinolytic Agents - adverse effects; Humans; Infusions, Intravenous; Intracranial Hemorrhages - chemically induced; Ischemic stroke; Male; Middle Aged; Neurology; Peptides - adverse effects; Peptides - therapeutic use; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - therapeutic use; Recombinant Proteins - administration & dosage; Risk Factors; Severity of Illness Index; Stroke - diagnosis; Stroke - drug therapy; Thrombolytic Therapy - adverse effects; Time Factors; tissue plasminogen activator; Tissue Plasminogen Activator - administration & dosage; Tissue Plasminogen Activator - adverse effects; Treatment Outcome; United States
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2013.12.012

Background The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue Plasminogen Activator (rt-PA) in Acute Ischemic Stroke-Enhanced Regimen (CLEAR-ER) trial found that intravenous rt-PA plus eptifibatide (combination arm) in acute ischemic stroke (AIS) was safe and had a direction of effect that would justify a phase III trial. CLEAR-ER had unanticipated imbalances between treatment groups. We compared the rates of symptomatic intracranial hemorrhage (sICH) and good outcomes for combination therapy patients in the CLEAR-ER trial to a matched cohort of rt-PA patients from the National Institute of Neurological Disorders and Stroke (NINDS) trial. Methods CLEAR-ER was a multicenter, double-blind, randomized study; rt-PA–eligible AIS patients were randomized to .6 mg/kg rt-PA plus eptifibatide (135 mcg/kg bolus and .75mcg/kg/min two-hour infusion) versus standard rt-PA (.9 mg/kg). For this analysis, we matched 1:1 CLEAR-ER combination therapy patients with rt-PA arm NINDS trial patients. Patients were matched by age, gender, race, baseline modified Rankin Scale score, baseline National Institutes of Health Stroke Scale (NIHSS) score, and stroke onset to rt-PA time. Results Fifty-four matches were made. One (1.8%) sICH occurred in each group (odds ratio [OR] 1.00, 95% confidence interval [CI] .01-78.50). At 90 days, 51.8% of the CLEAR-ER group had good outcomes versus 46.3% in the NINDS rt-PA group (OR 1.30, 95% CI .57-2.96). For subjects with baseline NIHSS score > 12 (CLEAR-ER median NIHSS score), 38.5% of the CLEAR-ER group had good outcomes versus 23.1% in the NINDS group (OR 2.33, 95% CI .60-9.02). Conclusions The safety and direction of effect of eptifibatide plus rt-PA were confirmed. A phase III trial is needed to determine the efficacy of eptifibatide plus rt-PA for improving long-term outcomes after AIS.