Rapid Treatment Remains Key for Thrombectomy in Acute Stroke but Still Works Several Hours After Onset

Patients with acute ischemic strokes caused by blockages in large intracranial blood vessels are most likely to derive a benefit from endovascular therapy when it is administered early after symptom onset, a pooled analysis of five trials confirms. But the interval in which outcomes can be improved appears to extend up to 7 hours and 18 minutes from onset.

The longer time window is “relevant from a policy and planning perspective,” senior author Michael Hill, MD (University of Calgary, Canada), told TCTMD. “It doesn’t mean you have time to be slow, but it means that you can expand your scope of the geographic distance [over which] you might be moving people to a central endovascular center.”

Moreover, “it really confirms what we all know, what we all have known physiologically, which is that the faster you treat patients the better they’re likely to do,” Hill said.

The findings, which were initially presented at the International Stroke Conference in February, were published in the September 27, 2016, issue of the Journal of the American Medical Association; the lead author is Jeffrey Saver, MD (University of California, Los Angeles).

‘Clinically Meaningful’ Relation to Time

Over the past few years, the publication of several trials has established that adding endovascular therapy—primarily with new-generation stent retrievers—to IV thrombolytic therapy improves functional outcomes among patients with ischemic strokes caused by large-vessel occlusions, leading to changes in recommendations and sparking discussions about how best to reorganize systems of care to provide the most benefit to patients.

To delve deeper into the impact of time to treatment on the efficacy of endovascular therapy, the investigators performed an analysis of individual patient-level data from five trials that were pooled as part of the HERMES collaboration. The trials—MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, and REVASCAT—enrolled 1,287 patients from 89 international sites.

At 90 days, the mean modified Rankin Scale (mRS) score was 2.9 in the patients who received endovascular therapy and 3.6 in those who received medical therapy alone.

The odds of having a better mRS score with endovascular therapy was highest among patients treated at 3 hours (common OR 2.79; 95% CI 1.96-3.98), declining as time went on. There remained a significant benefit in those treated at 6 hours (common OR 1.98; 95% CI 1.30-3.00), but not in those treated at 8 hours (common OR 1.57; 95% CI 0.86-2.88).

A similar relationship between longer time to treatment and waning efficacy was seen in the subgroup of patients who achieved substantial reperfusion with endovascular therapy (modified TICI score 2b or 3).

The differences based on time to treatment are “clinically meaningful,” the investigators say.

“Based on the current study, and assuming the findings are generalizable to the population of patients with acute ischemic stroke due to large-vessel occlusion,” they write, “among every 1,000 patients achieving substantial endovascular reperfusion, for every 15-minute faster emergency department door-to-reperfusion time, an estimated 39 patients would have a less-disabled outcome at 3 months, including 25 more who would achieve functional independence (mRS 0-2).”

Reorganizing Stroke Systems of Care

In an accompanying editorial, Steven Warach, MD, PhD, and S. Claiborne Johnston, MD, PhD (both University of Texas at Austin), state that “after nearly 2 decades since intravenous tissue plasminogen activator (IV tPA) became the first proven therapy for ischemic stroke, the findings from these trials indicated that major changes in stroke management and stroke systems of care were about to occur.”

And what is happening now, Hill said, is that regions are figuring out how best to centralize care to maximize the benefit. In Rhode Island, for example, two centers have been designated as endovascular centers and plans are being developed for the prehospital triage of patients, he reported.

How the stroke system will look will depend on how hospitals and the population are laid out in a given geographic area, he said, but “I think centralizing care makes a lot of sense.”

“If we get organized regionally, then there’s going to be a good opportunity to show population-wide improvement in health outcomes,” he added, acknowledging that conflicts are sure to arise if there are hospitals close together that both want to deliver endovascular services. That will likely require a political solution that brings together hospitals and providers of emergency medical services (EMS) and might involve sending patients back out to nonendovascular hospitals for recovery, Hill said.

Warach and Johnston point out that there is no consensus in the EMS community on the best way to triage patients to endovascular centers, but add that the question is one that is testable in clinical trials.

“The next major clinical trials in acute stroke therapeutics may be the testing of out-of-hospital strategies to improve outcomes with thrombectomy by substantially reducing times to reperfusion,” the editorialists write. “In the meantime, communities in the United States and in other developed countries will be evaluating new triage approaches, as previously occurred in the successful evolution of care for trauma and acute coronary syndrome.”

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