Adeoye O, Sucharew H, Khoury J, Tomsick T, Khatri P, Palesch Y, et al. Recombinant Tissue-Type Plasminogen Activator Plus Eptifibatide VersusRecombinant Tissue-Type Plasminogen Activator Alone in Acute Ischemic Stroke:Propensity Score-Matched Post Hoc Analysis. Stroke. 2015
This post-hoc propensity matched analysis of data gathered from the CLEAR-ER, IMS III, and ALIAS PART 2 trials attempted to shed some light on the potential efficacy of rt-PA plus eptifibatide and the need for phase III trials to further document its role in acute ischemic stroke.
The CLEAR-ER trial was a randomized trial which treated patients with either 0.6 mg/kg IV rt-PA versus 0.6 mg/kg of rt-PA plus eptifibatide (135 mcg/kg bolus and two hour infusion at 0.75 mcg/kg/min). This study was able to demonstrate the safety profile and favorable tendency of combination therapy vs IV rt-PA alone- but what results would be obtained if the combination therapy patients of CLEAR-ER were compared to the IV rt-PA patients of the IMS III and ALIAS PART 2?
To help determine that, eighty-five combination arm CLEAR-ER patients and 169 patients from the IMS III and ALIAS PART 2 trials were included in this analysis by a propensity score matching approach based on age, gender, race, baseline mRS, baseline NIHSS, and time from stroke onset to rt-PA initiation.
The primary outcome was defined as 90 day severity adjusted mRS dichotomization based on baseline NIHSS (favorable outcome if mRS= 0 with NIHSS ≤ 7; mRS= 0 or 1 with NIHSS 8-14; mRS= 0-2 with NIHSS >14). Secondary outcomes included 90-day mRS dischotomization as “excellent” (mRS 0-1); favorable (mRS 0-2); an analysis of the ordinal mRS; and, NIHSS of 0 or 1 at 24 hours.
At 90 days, it was observed that the combination rt-PA and eptifibatide group from the CLEAR-ER group had a greater proportion of patients with favorable outcomes (45% vs 36%., p=0.18). Secondary outcomes were 52% vs 34 % for excellent outcomes and 60% vs 53% for favorable outcomes. While a favorable direction towards combination therapy was observed, the study itself, as pointed out by the authors, is inherently limited by its post-hoc analysis and the small number of combination therapy patients available for analysis. Further trials should be pursued to determine if this analysis has any bearing for clinical practice.