Eptifibatide During Endovascular Therapy May Increase Risk of Parenchymal Hematoma Hemorrhage in LVO Stroke

After small studies suggested eptifibatide may be safe in acute ischemic stroke, new data showed similar rates of ICH between study drug and controls, but increased PH-2 for those treated with the antiplatelet.

Results from a single-center analysis showed that use of eptifibatide (Integrillin; Millennium Pharmaceuticals) during endovascular therapy (EVT) was associated with an increased rate of parenchymal hematoma (PH-2) hemorrhages, however the drug showed no significant differences on other outcomes, including 90-day modified Rankin Scale (mRS) scores, relative to controls.1

The findings were presented at the 2022 International Stroke Conference (ISC), February 9-11, in New Orleans, Louisiana, by lead author Ameena Rana, MD, resident, Cooper Medical School of Rowan University. In this study, 59 out of a total of 236 patients (25%) presenting with large vessel occlusion (LVO) stroke received eptifibatide and were matched with 3 control groups of 59 patients each, based on known factors associated with intracranial hemorrhage (ICH) risk. These included age, early infarct size, using Albert Stroke Program Tomography Scale (ASPECTS) score, and number of thrombectomy passes.

At baseline, all 4 of the groups had similar ASPECT scores, premorbid mRS scores, National Institutes of Health Status Scale (NIHSS) scores, and systolic blood pressure levels. In total, 41% of the cohort utilized IV thrombolysis (tPA), which was not significant (P = .22). At the conclusion of the analysis, neither of the groups differentiated on rate of ICH (P = .23), while PH-2 hemorrhages were significantly more frequent in the eptifibatide group compared with the control groups (21% vs 7%, 3%, and 0%, respectively; P = .0001).

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Between the eptifibatide and control groups, there were no significant differences in symptomatic ICH (7% vs 7%, 5%, and 2%, respectively; P = .57), 90-day mRS scores (P = .84), or 90-day mortality (P = .92). Rana et al wrote that, "larger prospective studies are needed to confirm these findings."

Eptifibatide, an antiplatelet drug of the glycoprotein IIb/IIIa inhibitor class, has been used to reduce the risk of acute cardiac events in patients with unstable angina or non-ST-segment elevation myocardial infarction both in patients who are to receive nonsurgical medical treatment and those undergoing percutaneous coronary intervention. The medication is administered IV and is available in strengths of 0.75 mg/ml and 2 mg/ml.

Smaller studies, including a 2016 paper by Harina Chahal et al, have also suggested that eptifibatide may be safe for treating LVO after tPA or during EVT. In that trial, 70 out 139 patients who met criteria received eptifibatide in addition to thrombectomy/intravenous (IV) tPA. The average dose was a bolus of 135 mcg/kg of eptifibatide followed by 0.5 mcg/kg/min continuous drip.2

At the conclusion of the study, no complications were reported, and patients recorded an improvement in NIHSS of 3.6 points, compared with 1.6 for those solely receiving IV tPA/thrombectomy. The paired mean difference was 2 (95% CI, .19-3.8; P = .03), favoring the addition of eptifibatide. These results showed that the addition of eptifibatide followed by a continuous drip for a mean of 24-hours to IV tPA/thrombectomy was associated with significantly better 24-hour post-procedure outcome. Chahal and colleagues concluded that this could be due to the suppression of inflammation and potential prevention of rethrombosis after treatment.

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1. Rana A, Yu S, Reid-Herrera S, et al. Safety of eptifibatide use in ischemic stroke patients undergoing endovascular therapy: a matched cohort analysis. Presented at ISC 2022; February 9-11. Abstract WP144
2. Chahal H, Mehta S, Moussavi M, et al. Eptifibatide is safe and may improve outcomes in stroke patients undergoing thrombectomy after receiving IVtPA. Neurology. 2016;86(16 supplement).