MR CLEAN: Time to endovascular treatment a strong determinant of stroke outcome
The timing of endovascular treatment (EVT) for acute ischaemic stroke is strongly associated with outcome, such that every hour of treatment delay from stroke onset reduces the odds of functional independence by more than 5 percent, according to real-world data from the MR CLEAN* registry.
“Functional outcome of patients who undergo EVT can be greatly improved by shortening onset to treatment times,” the authors said. “Reducing delays in the delivery of endovascular treatment should be a primary objective of all stroke centres that refer or treat patients with acute ischaemic stroke.”
The present analysis included 1,488 stroke patients (median age 71 years; 53 percent male) who underwent EVT. Following stroke onset, the procedure was performed <150 mins in 310 patients, 150–270 mins in 850 and 271–390 mins in 328. Successful reperfusion was achieved in 742 of 1,266 patients in whom thrombectomy was attempted.
Overall, median time from emergency department arrival to EVT initiation was 67 minutes (IQR, 41–103), with the procedure lasting a median of 63 minutes (IQR, 40–90). EVT duration was shorter when successful reperfusion was achieved (57 vs 85 minutes; p<0.01).
A shift toward poor functional outcome occurred with longer time to EVT initiation (adjusted common odds ratio for every hour, 0.83; 95 percent CI, 0.77–0.90). The odds of functional independence dropped from 47.3 percent at 90 minutes to 21.0 percent at 390 minutes. [Circulation 2018;138:232-240]
Specifically, each 60-minute delay in EVT was associated with a 5.3-percent lower probability of functional independence (modified Rankin Scale [mRS], 0–2) and a 2.2-percent increase in mortality, as well as a 7.7-percent reduced likelihood of functional independence among patients with successful reperfusion.
According to the authors, the findings confirm the following statement in the HERMES meta-analysis regarding time to EVT: “[S]ince imaging selection (ASPECTS thresholds, perfusion imaging and collateral imaging) was used to some degree in many of the enrolled patients, time effects observed in this pooled population are likely less than those that would occur in a population in which no imaging-selection whatsoever was used.” [JAMA 2016;316:1279-1288]
In other words, the effect of time to treatment on outcome weakens in a population in which strict patient selection for EVT has been applied, they continued. This is because additional imaging selection facilitates identification of patients who may be more tolerant to delays in onset to reperfusion.
“As such, additional imaging selection may play an important role in selecting EVT patients who arrive outside the 6-hour time window or after unwitnessed stroke onset,” the authors pointed out. “Strict selection of patients with evidence of salvageable tissue on brain imaging is an approach that could personalize the time window for individual patients and potentially widen the time window for the overall population of stroke patients, as recently shown [in a trial].” [N Engl J Med 2018;378:11-21;708-718]
In an accompanying editorial, Drs Abdulaziz S. Al Sultan and Michael D. Hill from the University of Calgary in Canada described the present data as valuable. [Circulation 2018;138:241-243]
“[The MR CLEAN registry] has an impressive, near-complete data collection and is an exemplar for medical and surgical registries globally… The implications of this real-world evidence further emphasize the importance of speed,” they said.
Al Sultan and Hill believe that the results are highly likely to be true, even though some baseline patient factors (eg, male sex, younger age, lower prestroke mRS, less likely to have atrial fibrillation) may have potentially contributed to a better outcome for patients treated earlier in the trial.
The experts reasoned that the real-world evidence data are very similar to those reported in previous trials and have a very strong biological plausibility based on the current understanding of the pathophysiology of human stroke.
“The penumbra, or amount of brain salvageable with reperfusion, will erode with progressive duration of ischaemia. Faster treatment results in greater tissue salvage and associated improved outcomes,” they said.
*Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands