Delays in restoring blood flow to the brain after acute ischemic stroke were associated with reduced benefits after intra-arterial clot-busting treatment and reduced chances for a good outcome, according to research published in JAMA Neurology.

To examine how the time from stroke onset to the start of treatment and how the time from stroke onset to reperfusion would affect the effectiveness of intra-arterial treatment (IAT), Diederik W.J. Dippel, MD, PhD, of Erasmus MC University Medical Center in Rotterdam, the Netherlands, and colleagues conducted a randomized clinical trial of 500 patients, of which 233 were assigned to intervention with IAT (for the most part, with retrievable stents), and 267 were assigned to no IAT. All patients received usual treatment, which included intravenous treatment (IVT) with clot-busting medication if needed.

The researchers defined time to the start of treatment as the time from onset of stroke symptoms to groin puncture (TOG) for catheter placement. They defined the time of onset of treatment to reperfusion (TOR) as the time it took to either reopen vessel blockage or the end of the procedure in cases where reperfusion was not achieved.

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Among the 500 patients, the median TOG was 260 minutes (4 hours, 20 minutes) and the median TOR was 340 minutes (5 hours, 40 minutes). Of the 233 patients assigned to intervention with IAT, 17 (7.3%) did not reach the intervention room, 25 (10.7%) started treatment within 3 hours of stroke onset, 96 patients (41.2%) started treatment between 3 and 4.5 hours after stroke onset, and 95 patients (40.8%) started treatment more than 4.5 hours after stroke onset, including 19 patients (8.2%) for whom treatment started more than 6 hours after stroke onset.

The researchers did not find a statistically significant association between TOG and the effect of IAT.

However, they did find an association between TOR and the effect of IAT. The researchers calculated that for every hour of delay before reperfusion, the initially large benefit of IAT decreases, and the absolute risk difference for a good outcome is reduced by 6%.

“This study highlights the critical importance of reducing delays in time to IAT for patients with acute ischemic stroke. The absolute treatment effect and its decrease over time are larger than those reported for intravenous treatment. … Most important[ly], our findings imply that patients with acute ischemic stroke should undergo immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion,” the authors conclude.


Fransen PSS, Berkhemer OA, Lingsma HF, et al. Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2015; doi:10.1001/jamaneurol.2015.3886.