Intraarterial Alteplase After Thrombectomy May Improve Stroke Recovery: CHOICE2

Adjunctive intraarterial alteplase (Activase; Genentech) following successful thrombectomy for acute ischemic stroke due to large-vessel occlusion demonstrated potential to increase the likelihood of full recovery in the phase 3 CHOICE2 trial (NCT05797792).1 The findings, presented at the 2026 International Stroke Conference (ISC) held in New Orleans, Louisiana, suggest the 2-pronged approach has potential to improve historically suboptimal outcomes in patients who underwent successful thrombectomy alone.

Excellent functional outcomes—defined as an mRS score of 0 to 1—were more common among patients who received adjunctive alteplase vs thrombectomy alone, with a 15% adjusted risk difference. | Image credit: vegefox - stock.adobe.com

Roughly 1 in 4 ischemic strokes are caused by large-vessel occlusion,2 and more than half of patients who undergo successful thrombectomy do not experience full recovery by 90 days post thrombectomy, according to study author Ángel Chamorro, MD, PhD, professor of neurology at the University of Barcelona and head of the Comprehensive Stroke Center Hospital Clinic in Barcelona.

“Despite successful angiographic reperfusion, fewer than one-third of patients treated with thrombectomy achieve an excellent functional outcome, defined as a [modified Rankin Scale] rating of 0-1 at day 90,” Chamorro said during a presentation of the late-breaking data at ISC 2026. He noted that there are several explanations for these results, but the main hypothesis is that the persistence of microvascular hypoperfusion has a significant impact.

Alteplase, a “clot-buster” medication used to treat ischemic stroke, acute myocardial infarctions, and acute pulmonary embolism,3 may improve functional outcomes for patients following acute ischemic stroke caused by large-vessel occlusion by enhancing microvascular perfusion further after thrombectomy.1

The CHOICE2 final results reported at ISC 2026 included 400 patients who were randomized to receive either thrombectomy alone (n = 219) or thrombectomy with adjunctive intraarterial alteplase within 24 hours (n = 214) at 14 centers in Spain. Functional status at 90 days based on the modified Rankin Scale (mRS) was the main end point in the study, and key secondary outcomes included microvascular hypoperfusion on CT perfusion (CTP) and infarct expansion ratio at follow-up.

Excellent functional outcomes—defined as an mRS score of 0 to 1—were more common among patients who received adjunctive alteplase (57.5%) vs thrombectomy alone (42.5%), with a 15% adjusted risk difference (95% CI, 5.7%-24.3%; P = .002).

Patients who received adjunctive alteplase were also less likely to have inadequate blood flow in small vessels based on imaging compared with the thrombectomy alone group (28.6% vs 50.5%, respectively), with an adjusted risk difference of –22% (–31.5% to –12.4%; P < .001).

Regarding day-to-day activity, patients who received adjunctive alteplase rated themselves higher when it came to mobility, self-care, performing usual activities, lower pain/discomfort, and depression/anxiety.

“These results are practice-informing but not yet practice-changing on their own,” Chamorro said in a news release.4 “While CHOICE2 strengthens the evidence that intra-arterial alteplase given after successful thrombectomy can improve recovery, broader adoption will require confirmation in additional studies, guideline review and careful consideration of patient selection.”

Those who received alteplase were not significantly more likely to have a brain bleed (1.4% vs 0.5%; P = .33). Regarding mortality, there was a significantly higher likelihood of mortality in the treatment vs placebo group (12.1% vs 6.4%; P = .04). The apparent difference in mortality is likely due to a low event rate in the control group, Chamorro explained.

CHOICE2 built upon favorable preliminary results from the CHOICE trial (NCT03876119), which found that adjunctive alteplase in addition to thrombectomy significantly improved outcomes among patients recovering from acute ischemic stroke.5

“Importantly, this approach should not be viewed as a ’one-size-fits-all’ treatment,” Charmorro said in the statement.4 “It is most likely to benefit patients who, despite large-vessel reopening, have evidence of inadequate blood flow in their microcirculation. However, if future studies and meta-analyses confirm the safety of this strategy, it may eventually reduce the need to rely on advanced imaging techniques to identify patients with persistent perfusion abnormalities appropriate for this treatment.”

References

1. Renu A, Amaro S, Urra X, et al. The chemical optimization of cerebral embolectomy (CHOICE2) trial: main results. Presented at: International Stroke Conference 2026; February 3-6, 2026; New Orleans, LA. Abstract LB001

2. Rennert RC, Wali AR, Steinberg JA, et al. Epidemiology, natural history, and clinical presentation of large vessel ischemic stroke. Neurosurgery. 2019;85(suppl 1):S4-S8. doi:10.1093/neuros/nyz042

3. Activase. Prescribing Information. Genentech; 2022. Accessed February 4, 2026. https://www.gene.com/download/pdf/activase_prescribing.pdf

4. Infusion of clot-buster medication after clot removal may improve stroke recovery. News release. American Heart Association. February 4, 2026. Accessed February 4, 2026. https://newsroom.heart.org/news/infusion-of-clot-buster-medication-after-clot-removal-may-improve-stroke-recovery

5. Renú A, Millán M, San Román L, et al. Effect of intra-arterial alteplase vs placebo following successful thrombectomy on functional outcomes in patients with large vessel occlusion acute ischemic stroke: the CHOICE randomized clinical trial. JAMA. 2022;327(9):826-835. doi:10.1001/jama.2022.1645