The CHOICE-2 randomized clinical trial demonstrates a major step forward for patients with acute ischemic stroke. Researchers found that administering intra-arterial alteplase after thrombectomy significantly improves 90-day functional outcomes. While mechanical thrombectomy successfully clears large vessel occlusions, microvascular blockages often persist. Consequently, this adjunctive therapy addresses the "no-reflow" phenomenon by targeting the distal microcirculation. These findings provide a compelling case for enhancing standard care protocols in specialized stroke centers.

Clinical Impact of Intra-Arterial Alteplase After Thrombectomy

The trial enrolled 440 patients who achieved successful macrovascular reperfusion after their initial thrombectomy. Clinicians randomized these participants to receive either a 15-minute infusion of intra-arterial alteplase (0.225 mg/kg) or thrombectomy alone. Notably, 57.5% of the alteplase group achieved an excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0 or 1. In contrast, only 42.5% of the control group reached this milestone. This 15% absolute improvement suggests a number needed to treat (NNT) of just seven to achieve one additional excellent outcome. Therefore, the results strongly support using this adjunctive strategy to maximize recovery potential.

Improving Microvascular Perfusion and Safety Outcomes

One primary reason for suboptimal recovery after successful thrombectomy is persistent microvascular hypoperfusion. Specifically, the CHOICE-2 data showed that the alteplase group had significantly lower rates of residual hypoperfusion (28.6%) compared to the control group (50.5%). This 22% reduction indicates that the thrombolytic effectively clears distal micro-clots that mechanical devices cannot reach. Furthermore, the safety profile remained manageable. The study observed symptomatic intracranial hemorrhage in only 1.4% of the intervention group versus 0.5% in the control group. Although mortality was numerically higher in the alteplase arm (12.1% vs 6.4%), investigators attributed this to an unexpectedly low death rate in the control group rather than treatment toxicity.

Implementation in Clinical Practice

Moreover, the benefit of this approach remained consistent across various patient subgroups. Whether or not patients received intravenous thrombolysis prior to the procedure, the addition of intra-arterial alteplase after thrombectomy provided measurable advantages. Medical educators emphasize that while these results are practice-informing, clinicians must still carefully select patients based on angiographic success and tissue viability. Ongoing research will likely refine which patients derive the greatest benefit from this dual-intervention approach.

Frequently Asked Questions

What was the specific dosage used in the CHOICE-2 trial?

The trial utilized a dose of 0.225 mg/kg of alteplase, with a maximum total dose of 20 mg, infused over 15 minutes directly into the target artery.

Does adjunctive intra-arterial alteplase increase the risk of brain bleeds?

No, the CHOICE-2 trial found no significant difference in symptomatic intracranial hemorrhage rates between the intervention group (1.4%) and the control group (0.5%).

Which patients were eligible for the CHOICE-2 study?

Eligible participants included adults with large vessel occlusion stroke who achieved successful reperfusion (eTICI score 2b50 to 3) within 24 hours of symptom onset.

Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice. Always seek the advice of a physician or other qualified health provider with any questions regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

Renú A et al. Adjunctive Intra-Arterial Alteplase After Successful Thrombectomy for Acute Ischemic Stroke: The CHOICE-2 Randomized Clinical Trial. JAMA. 2026 May 07. doi: 10.1001/jama.2026.5164. PMID: 42096239.

Chamorro Á et al. Intra-arterial Alteplase Versus Placebo After Mechanical Thrombectomy for Acute Ischemic Stroke (CHOICE): A Randomized Clinical Trial. JAMA. 2022 Mar 1;327(9):826-835.

Goyal M et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016 Apr 23;387(10029):1723-31.