ISC 2026 | Main results from CHOICE2: intra-arterial alteplase following thrombectomy in large vessel occlusion

CHOICE2 is a trial that was designed mainly because CHOICE1 was interrupted prematurely because of a placebo shortage, which is a very unusual cause to terminate prematurely a clinical trial. So in CHOICE1, we found a very exciting result, and that was an 18% absolute increment in the proportion of patients with excellent outcome at 90 days after thrombectomy and successful angiographic results. So when most people consider that when you have a full angiography normalized, there’s not much left to be done with your therapies, we start our job thinking that a normal angiography does not reflect that the brain tissue is adequately perfused. So CHOICE1 was extremely exciting, so exciting that some people doubt that this could reflect reality. So CHOICE2 was mainly designed to validate the use of intra-arterial alteplase following a successful thrombectomy in patients with large vessel occlusion.

CHOICE2 was done in Spain, only in Spain, in 14 tertiary centers. It’s investigator-driven, is publicly funded, and prospectively registered. And the inclusion criteria were similar to CHOICE1, patients treated with thrombectomy and obtaining a TICI score of 2B or 3, indicating at least 50% reperfusion of the ischemic brain without contraindication to the use of alteplase. Patients were randomized one-to-one to thrombectomy alone or to thrombectomy plus intra-arterial alteplase, dose-adjusted to a maximum dose of 20 milligrams. The primary outcome was the rate of patients with a Rankin zero to one at 90 days. But importantly, and different from CHOICE1, a key secondary outcome was the proportion of patients with abnormal findings on CT perfusion, which was mandatory at 36 plus minus 24 hours after therapy. Other secondary outcomes include the Barthel Index, the quality of life, and safety measures included the rate of symptomatic intracerebral hemorrhage and death. All the outcomes, clinical and imaging outcomes in CHOICE2 were centralized and analyzed by blinded reviewers outside of the management of the trial. And for sample size calculation, we used the data obtained in CHOICE1. So the trial was powered to demonstrate superiority if at least there was a 14% absolute difference in favor of intra-arterial alteplase compared to the control group.

So during the study period, the study was terminated in 17 months, which is a great success because that indicated that 1.7 patients per site per month were included. 440 patients were randomized in this 17 months, and of these 214 were randomized to thrombectomy plus intra-arterial alteplase, and 219 were randomized to thrombectomy alone and included in the primary analysis.

The baseline characteristics between the two treatment groups were quite similar, with the exception of the median age, which was two years older in the alteplase group compared to the placebo. So no risk of bias in that respect. All the causes were quite similar between the groups. And so the primary efficacy outcome showed that the proportion of patients with an excellent outcome in the intra-arterial alteplase group was between 57.5% and in the control group was 42.9%. This is an adjusted risk difference of 15%, absolute difference, with a confidence interval between 5.7 and 24.3%, meaning that the p-value was 0.002. That is, that CHOICE2 was a magnificent positive clinical trial. Only seven patients need to be treated to get one more patient with an excellent outcome.

Other secondary outcomes were also very informative because we understand the mechanism for such a huge clinical response. The proportion of patients with abnormal perfusion on CTP at follow-up was 29% in the intra-arterial alteplase group and 51% in the control group, yielding a difference of minus 22% absolute difference in the proportion of patients with abnormal perfusion on CTP, leading to a p-value of less than 0.001. So the proportion of hypoperfusion was also highly significant. The infarction expansion rate was another secondary outcome, it was smaller in the active group but the difference did not meet statistical significance. The Barthel Index, the proportion of patients with independency at 90 days was 64% in the active group and 58% in the control group, this difference is not significant. But if we concentrate the Barthel Index, the activity of daily living, only in stroke survivors, the differences were statistically significant, in favor of the active group as well. The shift analysis of the Rankin score, measuring all the strata of the scale, showed a trend of 0.08 in favor of the active group. Another important finding, the quality of life self-reported by the patients showed a highly significant difference in favor of the active group compared to the controls. And this was reported by the patients, not by the investigators. Regarding safety, there was a very low rate of bleeding, symptomatic bleeding in both groups, 1.4% in the active group, 0.5% in the control, no significant differences. And there was also a very low mortality rate in the two groups, 12% in the active group and 6.4% in the control. That is a significant increment in the rate of death in the active group in this occasion. So the subgroup analysis, all of them, the pre-specified subgroup analyses showed better results in the active group compared to the control, regardless of the previous use of systemic thrombolysis, being male or female, having a TICI 2B or 3 at the end of thrombectomy, being male or female, having low glucose or high glucose. So in all the pre-specified groups, the therapy was better than the control group.

So the conclusions are evident. What is the use of intra-arterial alteplase following a successful thrombectomy? The first one is that it increases the rate of excellent functional outcome and decreases the persistence of hypoperfusion. The second one is that it improves the patient-reported quality of life and the rates of full independence in daily activity among stroke survivors. It does not increase the risk of bleeding, and it provides an increased mortality, which is mainly driven by a very unexpected low control group rate in the control group. So as a corollary, we can say that CHOICE2 clearly supports the consideration of the use of intra-arterial alteplase after a successful thrombectomy in selected patients.

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