For July 2020, we have selected: Yang P. et al. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke
N Engl J Med 2020;382(21):1981-1993. doi: 10.1056/NEJMoa2001123.
It is well known that endovascular thrombectomy is the standard treatment for
patients who have acute ischemic stroke due to large-vessel occlusion in the anterior cerebral circulation.
Our paper of the month deals with the ongoing debate regarding the use of intravenous alteplase before and during thrombectomy. Indeed, it reports the first investigator-initiated, multicenter, prospective, randomized, open-label trial with blinded outcome assessment involving patients with acute ischemic stroke who were eligible both to receive intravenous alteplase and to undergo endovascular thrombectomy with the aim of investigating whether endovascular thrombectomy alone would be noninferior to combined treatment with endovascular thrombectomy preceded by intravenous alteplase in this group of patients.
656 patients with large vessel occlusion acute ischaemic stroke were recruited from 41 academic tertiary care centers in 18 provinces in China, which were centres with at least 30 endovascular thrombectomy procedures during the previous year. 327 patients were assigned to the thrombectomy-alone group and 329 were assigned to the combination-therapy group.
Inclusion criteria were: age of 18 year or older; presence of an occlusion of the intracranial segment of the internal carotid artery or of the first or proximal second segment of the middle cerebral artery or both showed on computed tomographic angiography, which could be treated with intravenous alteplase within 4.5 hours after symptom onset; presence of a neurologic deficit (evaluated by the National Institutes of Health Stroke Scale).
Exclusion criteria included: presence of a disability before the stroke; contraindications to intravenous alteplase according to the American Heart Association–American Stroke Association guidelines.
The median age of the patients was 69 years and 56.4% were male.
As primary outcome, this study showed that thrombectomy alone was noninferior to combination thrombectomy with intravenous alteplase treatment because the lower boundary of the confidence interval was greater than the prespecified value of 0.8 (unadjusted common odds ratio, 1.09; 95% CI, 0.84 to 1.43; P = 0.02).
As secondary outcomes, mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group. The percentage of patients with successful reperfusion before thrombectomy was 2.4% in the thrombectomy-alone group and 7.0% in the combination-therapy group, and successful reperfusion on final angiography was observed in 79.4% and 84.5%, respectively. Of note, this study did not show any difference regarding safety between the two groups. Indeed, 37% patients of the thrombectomy-alone group had serious adverse events during the 90-day follow-up period versus 36.8% in the combination-therapy group. Similarly, procedural complications occurred in an equal % in both groups. This study opens a new scenario in the treatment of acute ischaemic stroke produced by occlusion of large vessels in the anterior circulation taking into account the risk of hemorrhage and the cost of intravenous alteplase. Larger trials performed in other countries and different healthcare systems are needed to compare alteplase plus endovascular therapy with endovascular therapy alone.
This is a very important study that attempted for the first time to answer a clinical relevant question whether limitation of thrombolytic therapy with alteplase (rtPA) prior to thrombectomy has an additional benefit over direct thrombectomy without preceding rtPA. The study results showed that the direct thrombectomy was non inferior to the administration of IV thrombolysis prior or during the endovascular procedure. I would like to emphasis that the margin used in this trial to declare non inferiority was very generous (20%).
Comment from Prof Natan Bornstein: It is interesting to note that in the combined group the reperfusion was higher than in the thrombectomy alone group but surprisingly it was not translated into clinical benefits. It might be that the IV rtPA in most of the patients was given only for a short time and not the full dose. Another point that should be taken into consideration is the generalizability of the trial results which are different from the previous thrombectomy trials regarding the favorable outcome (36.6% vs. 46%). It could well be that the effect of thrombectomy in Chinese patients is different than in the Caucasian population enrolled to the previous trials. In my opinion we should wait for the results of the currently ongoing similar trials in order to draw a firm conclusion on this important clinically relevant question.
Dr. Bersano from the Cerebrovascular Unit of the Foundation Carlo Besta Neurological Institute, Milan, Italy said: “Whether to administrate alteplase before thrombectomy provides additional benefits over thrombectomy alone is a matter of debate. The administration of alteplase before initiating thrombectomy could favour thrombi dissolution and partial vessel recanalization. Conversely a pre-treatment with alteplase may be associated with a delay of the endovascular procedure and an increased risk of cerebral heamhorrage. The DIRECT MT trials, reported in the EAN pages as paper of the month, showed, interestingly, that trombectomy alone was non inferior to combined therapy in a Chinese population with large anterior vessel ischemic strokes. These findings could lead us to send patients with anterior circulation large vessel occlusion strokes directly to thrombectomy without administering alteplase. However, in the paper only 23 of the patients undergone to the combined therapy completed the infusion before groin puncture and most of them (86.5%) completed the infusion during endovascular treatment. This finding, that could influence the results of the study, could not completely reflect the clinical ground, since in most countries intravenous thrombolysis is often initiated at primary stroke centers and, thus, terminated before starting thrombectomy. Moreover, the vessel reperfusion rate was observed to be superior in patients undergone to combined therapy in comparison to the thrombectomy alone group. Although in this study reperfusion rate does not seem to influence clinical outcome, this data could support a possible advantage of an early administration of alteplase before thrombectomy. In this context our cinical practice should not change, waiting for the results or additional ongoing trials.