Zinkstok SM, Roos YB; on behalf of the ARTIS investigators.
University of Amsterdam, Amsterdam, The Netherlands.
Editor’s note: Based on the premise that early administration of antiplatelet therapy might reduce the rate of re-occlusion after stroke thrombolysis, these authors designed a multicenter, randomized, controlled, prospective trial of acute stroke thrombolysis with or without the addition of aspirin administered early. They randomized patients who were treated with recombinant tissue plasminogen activator (rtPA) intravenously within 4.5 h of symptom onset to receive either standard therapy (in which no antiplatelet therapy is given for 24 h post-thrombolysis) or 300 mg aspirin intravenously within 90 min of the start of thrombolytic therapy. The primary endpoint of this trial was a favorable outcome at 3 months, defined as a modified Rankin Scale (mRS) score ≤2, with secondary endpoints that included the development of symptomatic intracranial hemorrhage (sICH), defined as imaging evidence of ICH on a follow-up computed tomography scan, combined with a neurological deterioration of ≥4 points on the National Institutes of Health Stroke Scale (NIHSS). The ARTIS (Antiplatelet Therapy in Combination with rtPA Thrombolysis in Ischemic Stroke) trial was set up with the intention of recruiting 400 patients to each group, but was stopped early on the recommendation of the data-monitoring committee after only 642 patients had been recruited. The reason for halting recruitment was on the grounds of safety, as the investigators had detected a significant excess of reported sICH in the aspirin-treated group. Although the primary outcome did not differ between the two groups, and the main determinant of poor outcome in both was the initial stroke, there were 14 occurrences of sICH in the aspirin group compared with five in the standard treatment group (4.3% vs. 1.6%; p=0.04). Furthermore, sICH was the determinant of poor outcome in 11 patients in the aspirin group, compared with one in the standard treatment group, although this difference was not significant (p=0.06). Although the trial was stopped early, it seems unlikely that it would have demonstrated benefit for early administration of aspirin on the primary outcome measure, as there was no evidence of a trend towards this in their analysis. The safety concern was an unexpected but important finding, and leads to the conclusion that the current practice of withholding antiplatelet therapy for 24 h after intravenous thrombolysis should continue.