HONOLULU—The combination of eptifibatide and IV t-PA may be safely used to treat patients within three hours of ischemic stroke onset, according to research reported at the 2013 International Stroke Conference. The two drugs are associated with a lower rate of symptomatic intracranial hemorrhage at 36 hours.
Study Population Was Similar to Clinical Population
Opeolu Adeoye, MD, Assistant Professor of Emergency Medicine at the University of Cincinnati, and colleagues conducted a multisite, double-blind, randomized, phase II study to examine the safety of an eptifibatide–t-PA combination in patients with ischemic stroke. The investigators enrolled 126 patients between ages 18 and 85 with a baseline NIH Stroke Scale (NIHSS) score greater than 5. The study included patients with baseline disability so as to approximate the real-world population of patients with stroke that would be treated with the regimen. Investigators sought to randomize patients five to one, using minimization techniques, to the combination therapy or standard-dose t-PA.
The intervention group received 0.6 mg/kg of t-PA administered over 40 minutes, combined with a 135-µg/kg bolus of eptifibatide, and followed by an infusion of 0.75 µg/kg/min administered over two hours. The primary safety end point was the incidence of symptomatic intracranial hemorrhage within 36 hours. The primary efficacy end point was a modified Rankin Scale score (mRS) of 0 or 1 at 90 days or a return to baseline mRS. The investigators stipulated that they would not proceed to phase III trials if the proportion of patients in the study who achieved good outcomes was below 33%.
Good Outcomes More Common With Combination Therapy
A total of 101 patients received combination therapy, and 25 patients received t-PA alone. Dr. Adeoye noted several unexpected disparities between the treatment and control groups. Participants in the combination therapy group tended to be younger and to have had less severe strokes than the participants who received t-PA only. The researchers also observed a slightly higher proportion of combination therapy patients with a baseline Rankin score of 0 or 1 than control patients.
Approximately 2% of subjects in the combination therapy arm had symptomatic intracranial hemorrhage in 36 hours, compared with 12% of patients who received only t-PA. Rates of other bleeding were similar between the two groups. About 20% of patients in the combination therapy arm were dead at 90 days, compared with 16% of patients who received t-PA only. The rate of stroke-related deaths was 15% in the combination group, compared with 16% in the standard t-PA group.
In the combination therapy arm, 49.5% of patients had an mRS of 0 or 1 or returned to baseline modified Rankin score at 90 days, compared with 36% of patients in the t-PA only arm. After adjusting the observed proportion of good outcomes for the imbalances in age, NIHSS, and time to t-PA, the researchers found an estimated effect size of 8%, with a relative risk of 1.16. The bulk of the treatment effect appeared to be in patients with an NIHSS score greater than 12. This result suggests that vessels were no longer occluded after treatment, according to Dr. Adeoye.
The study “was neither designed nor powered to assess efficacy,” said Dr. Adeoye. “After adjusting for the imbalances observed, what we think is a clinically meaningful treatment effect persisted between the two groups. Based on that, we conclude that eptifibatide may be safely combined with medium-dose IV t-PA administered within three hours of symptom onset to stroke patients. A phase III trial, we believe, is warranted,” he concluded.
—Erik Greb
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