Stroke Trial Tips Scale Further to Favor Intra-Arterial Lytic After EVT

 This doesn't get you 100% recovered, so you're STILL APPROVING FAILURE AS A MATTER OF COURSE!

Stroke Trial Tips Scale Further to Favor Intra-Arterial Lytic After EVT

CHOICE-2 supports intra-arterial alteplase after successful reperfusion(Success is 100% recovery, quit trying to justify failure by using your tyranny of low expectations! Reperfusion is only the first step, what are the EXACT FOLLOWON STEPS TO 100% RECOVERY?)

NEW ORLEANS -- A stronger case could be made for intra-arterial (IA) alteplase after successful mechanical thrombectomy based on more randomized data, this time the CHOICE-2 trial from Spain.

In acute ischemic stroke patients with large vessel occlusions who achieved majority-complete reperfusion with endovascular therapy (EVT), adjunctive IA alteplase further increased the likelihood of good functional outcomes when given in the 24-hour window. Ninety-day modified Rankin Scale (mRS) scores of 0-1 were significantly more likely after alteplase treatment compared with EVT alone (57.5% vs 42.9%, P=0.002).

Moreover, alteplase improved the secondary outcomes of CT perfusion and patient-reported quality of life.

"Let me announce happily that CHOICE-2 is a positive clinical trial," said Ángel Chamorro, MD, PhD, of the University of Barcelona and Hospital Clinic of Barcelona, to applause at the International Stroke Conference.

With the number needed to treat being seven patients, "let me remind you that this is approximately the number needed to treat patients with IV thrombolysis within 3 hours from the onset of symptoms, compared to placebo. So I think this is a remarkable figure," he added.

As for the safety of IA alteplase, the results were mixed: no excess symptomatic intracerebral hemorrhage was detected at 36 hours (1.4% vs 0.5% for controls, P=0.33), but death at 90 days was significantly more likely in the treated group (12.1% vs 6.4%, P=0.04).

Chamorro argued that the apparent difference in mortality likely reflects an "extremely low" event rate among control patients in CHOICE-2. Indeed, in the older PEARL trial, all-cause mortality occurred in 17.1% of patients who received adjunctive IA alteplase and 11.3% of those who received EVT alone, a nonsignificant difference.

The benefit of using adjunctive IA thrombolytics is based on frequent observations that EVT patients often still have functional impairments; lingering microvascular hypoperfusion is believed to be the culprit.

The original CHOICE trial had been stopped early due to a shortage of the placebo, Chamorro said. However, it did suggest benefit with IA alteplase for stroke patients with successful angiographic reperfusion: there was an improvement in the mRS score at 90 days with alteplase 0.225 mg/kg, maximum 22.5 mg (a slightly different dose to CHOICE-2's maximum 20 mg over a 15-minute infusion).

More recently, promising results have been reported with clot-busters after successful EVT, namely IA tenecteplase in ANGEL-TNK and IA alteplase in PEARL, both presented last year. However, there's also been disappointing results in the POST-TNK and POST-UK trials in which adjunctive IA tenecteplase and urokinase, respectively, fell short in achieving longer survival without disability after EVT.

American stroke guidelines, updated last week, thus state that adjunctive IA thrombolytics with urokinase, alteplase, or tenecteplase "may be reasonable" to improve cerebral reperfusion and 90-day functional outcomes in stroke patients with complete or near-complete EVT (class IIb recommendation).

"The usefulness of administration of adjunctive intra-arterial thrombolytics, namely urokinase and tenecteplase, after successful thrombectomy remains uncertain, as data from four major [randomized controlled trials] are conflicting," the guideline authors reasoned.

The open-label CHOICE-2 trial was conducted at 14 Spanish centers with blinded assessment of clinical and imaging outcomes.

The study included stroke patients with large vessel occlusions with majority-complete reperfusion (expanded Thrombolysis in Cerebral Infarction grade [eTICI] 2b50-3) post-EVT who had been treated within 24 hours of stroke onset. The Alberta Stroke Program Early CT Score (ASPECTS) could not be below 6, and patients were excluded if they had an NIH Stroke Score of 25 or higher or if they had contraindications to alteplase.

Ultimately, 440 participants were randomized to EVT alone or with IA alteplase. The median cohort age was around 76 years, and the group was roughly split between the sexes. Median NIH Stroke Score was 15, about 64% had a preceding IV thrombolysis, and cause of stroke was cardioembolic in nearly half of cases.