September 27, 2016
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Early endovascular treatment benefits patients with large-vessel ischemic stroke

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In patients with large-vessel ischemic stroke, earlier intervention with endovascular thrombectomy and medical therapy is linked to a lesser extent of disability at 3 months vs. medical therapy alone, according to recent findings.

In the meta-analysis, researchers pooled demographic, clinical and brain imaging data of 1,287 participants (mean age, 67 years; 47% women) in five randomized, phase 3 trials conducted at 89 international locations.

Trials identified for analysis included those in which most endovascular treatments involved the use of stent retrievers or other second-generation devices published by July 1, 2016.

The researchers reviewed the pooled data to analyze the associations between time to treatment and outcomes in patients randomly assigned to thrombectomy plus medical therapy (n = 634) or medical treatment alone (n = 653).

The study’s primary outcome was the extent of disability (modified Rankin Scale score range, 0-6) at 3 months, evaluated with the common OR to reveal changes in the dissemination of disability over the modified Rankin score range. Secondary outcomes consisted of 3-month functional independence, 3-month mortality and symptomatic hemorrhagic alteration. The time from symptom onset to randomization was 196 minutes (interquartile range [IQR], 142-267). Of the patients randomly assigned to endovascular treatment, the time from symptom onset to arterial puncture was 238 minutes (IQR, 180-302) and the time from symptom onset to reperfusion was 286 minutes (IQR, 215-363).

Less disability

The researchers found that, at 3 months, the use of endovascular treatment was linked to a significantly lower extent of patient disability, with a mean modified Rankin score of 2.9 (95% CI, 2.7-3.1) in the endovascular cohort vs 3.6 (95% CI, 3.5-3.8) in the medical therapy group.

The common OR of a more favorable disability outcome with thrombectomy was 2.49 (95% CI, 1.76-3.53), with an absolute risk difference of 38.1% (P < .001), and earlier intervention was linked to a greater degree of benefit, according to the data.

The extent of benefit (modified Rankin score scale distribution) in the endovascular group showed nominal decreases with longer time from symptom onset to arterial puncture. In this group, the common OR at 3 hours was 2.79 (95% CI, 1.96-3.98), with an absolute risk difference for lower disability scores of 39.2%, the researchers reported. The common OR at 6 hours was 1.98 (95% CI, 1.3-3), with an absolute risk difference of 30.2%, and the common OR at 8 hours was 1.57 (95% CI, 0.86-2.88), with an absolute risk difference of 15.7%.

The statistical significance of this finding persisted through 7 hours and 18 minutes, the researchers wrote.

Of the 549 patients who were treated with endovascular thrombectomy and had available modified thrombolysis in cerebral infarction scores, 390 attained significant reperfusion, according to the data.

Among these patients, each 1-hour delay to reperfusion was correlated with a greater degree of disability (common OR =0.84; 95% CI, 0.76-0.93; absolute risk difference, –6.7%) and a lower level of functional independence (OR = 0.81; 95% CI, 0.71-0.92; absolute risk difference, –5.2%).

“There was some benefit of therapy up to 7 1/3 hours after onset — that’s an important new aspect,” Jeffrey L. Saver, MD, of David Geffen School of Medicine at UCLA, said in a press release. “If you get the artery open at 3 hours, 65% of patients will be able to live independently 3 months later. If it takes 8 hours to get it open, then only 45% will be able to live independently. It makes a major difference in outcome.”

Faster interventions

In a related editorial, Steven Warach, MD, PhD, and S. Claiborne Johnston, MD, PhD, both from Dell Medical School, University of Texas at Austin, wrote that these findings will likely drive concerted efforts to achieve faster interventions in patients with large-vessel ischemic stroke.

S. Claiborne Johnston

“The potential benefit of earlier times to thrombectomy that could be achieved by reducing workflow delays will require substantial system changes,” Warach and Johnston wrote. “Organizations that certify stroke centers may attempt to help improve outcomes by requiring endovascular-capable stroke centers to meet aggressive goals, such as 60 minutes from hospital arrival to arterial puncture and 90 minutes from hospital arrival to achievement of substantial reperfusion.” – by Jennifer Byrne

Disclosure: Saver reports financial ties with BrainsGate, Bristol-Myers Squibb, Boehringer Ingelheim, Cognition Medical, Covidien/Medtronic, Neuravi, Pfizer, St. Jude Medical, Stryker and ZZ Biotech. Please see the full study for a list of the other researchers’ relevant disclosures. Warach and Johnston report no relevant financial disclosures.