By Matthew E. Fink, MD

Professor and Chairman, Department of Neurology, Weill Cornell Medical College; Neurologist-in-Chief, New York Presbyterian Hospital

Dr. Fink reports he is a retained consultant for Procter & Gamble and Pfizer.

SOURCE: Saver JL, Goyal M, van der Lugt A, et al., for the HERMES Collaborators. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: A meta-analysis. JAMA 2016;316:1279-1288.

In 2015 and 2016, five prospective trials of endovascular thrombectomy for large vessel occlusions with second-generation devices were published and showed dramatic efficacy in terms of reperfusion and functional outcomes (N Engl J Med 2015;372:11; N Engl J Med 2015;372:1009; N Engl J Med 2015;372:1019; N Engl J Med 2015;372:2296; N Engl J Med 2015;372:2285; Lancet 2016;387:1723). In an attempt to obtain more information about the effect of time delays on outcomes, all of the investigators agreed to pool the data and analyze them as a larger group, with a specific goal of assessing the effects of “time to treatment” on the outcomes, and to what extent treatment delay was related to functional outcomes, mortality, and symptomatic hemorrhage. Clinical information, brain imaging data, as well as functional and imaging outcomes were pooled and analyzed from a group of 1,287 treated patients. The primary outcome was degree of disability, as measured by the modified Rankin scale (mRS) at three months, with common odds ratios calculated for various time intervals to show a distribution of outcomes related to time delays.

Among all 1,287 enrolled and randomized patients, 634 underwent endovascular intervention with a median time from symptom onset to randomization of 196 minutes (142 to 267). Median symptom onset to arterial puncture was 238 minutes (180 to 302) and time to reperfusion was 286 minutes (215 to 363). At 90 days, the mean mRS score was 2.9 (95% confidence interval [CI], 2.7-3.1) in the endovascular group and 3.6 (95% CI, 3.5-3.8) in the medical therapy group. The odds of reduced disability at 90 days in the endovascular group declined with longer time from symptom onset to arterial puncture: Odds ratio at 3 hours = 2.79, at 6 hours = 1.98, and at 8 hours = 1.57, retaining a statistical significance up to 7 hours and 18 minutes. Among the 390 patients who achieved substantial reperfusion with thrombectomy, each one-hour delay to reperfusion was associated with more disability and less functional independence. However, there was no difference in mortality due to delay. Overall, this meta-analysis of thrombectomy in patients with large vessel ischemic stroke demonstrated that earlier treatment compared with medical therapy alone was associated with lower degrees of disability at three months. Each hour delay resulted in worse outcome.