New research presented this week at the International Stroke Conference in New Orleans, Louisiana, suggests a significant improvement in recovery outcomes for stroke patients who receive a clot-busting drug, alteplase, directly into the brain artery after a mechanical thrombectomy. The phase 3 CHOICE2 trial demonstrated a 15% absolute increase in excellent functional outcomes in these patients.
Understanding Ischemic Stroke and Current Treatment
Ischemic stroke, the most common type of stroke, occurs when a blood clot blocks an artery supplying blood to the brain. This deprives brain tissue of oxygen and nutrients, leading to cell damage and potential long-term disability. Mechanical thrombectomy, a procedure where a catheter is guided through blood vessels to physically remove the clot, has become a standard treatment for large-vessel occlusion strokes – those caused by clots in major arteries.
However, even with successful thrombectomy, a substantial number of patients don’t achieve full recovery. This is often due to microvascular dysfunction – meaning smaller blood vessels downstream from the blockage remain impaired, hindering blood flow and oxygen delivery to the surrounding brain tissue. This phenomenon is sometimes referred to as “no-reflow.”
The CHOICE2 Trial: Adding Alteplase to Thrombectomy
The CHOICE2 trial, a randomized controlled study involving 400 patients across 14 Spanish centers, investigated whether adding intra-arterial alteplase – administering the clot-busting drug directly into the affected artery – after successful thrombectomy could improve outcomes. Patients were randomly assigned to receive either thrombectomy alone or thrombectomy plus intra-arterial alteplase.
The primary endpoint of the study was the modified Rankin Scale (mRS) score at post-stroke, a measure of functional independence. Researchers found that 57.5% of patients who received both thrombectomy and alteplase achieved an excellent outcome (mRS score of 0-1, indicating minimal or no disability), compared to 42.5% in the thrombectomy-alone group. This translates to the aforementioned 15% absolute risk difference, a statistically significant finding (P=0.002).
Improved Microvascular Reperfusion
CT perfusion imaging revealed a key mechanism behind the improved outcomes. Patients receiving alteplase showed significantly improved microvascular reperfusion – a 22% reduction in microvascular hypoperfusion – compared to those receiving thrombectomy alone (28.6% vs 50.5%; adjusted risk difference, –22%; P<.001). This suggests that alteplase helps restore blood flow not just in the main artery, but also in the smaller vessels downstream, mitigating the “no-reflow” phenomenon.
Patient-Reported Outcomes Also Show Improvement
Beyond clinical assessments, the study also incorporated patient-reported measures of recovery. Individuals who received alteplase reported improvements in mobility, self-care, usual activities, pain/discomfort, and depression/anxiety at follow-up, indicating a broader positive impact on quality of life.
Safety Considerations and Future Research
While the results are promising, the study also highlighted some safety considerations. Mortality was slightly higher in the group receiving alteplase (12.1% vs 6.4%; P=0.04). Symptomatic intracranial hemorrhage – bleeding in the brain – occurred at similar rates in both groups (1.4% vs 0.5%).
These findings underscore the need for further validation and careful patient selection. The dose of alteplase used in the trial was 0.225 mg/kg (with a maximum dose of 20 mg) infused over 15 minutes. Randomization occurred within 4.5 hours of stroke onset, or up to 24 hours for patients with salvageable tissue identified through imaging.
The CHOICE2 trial contrasts with some prior real-world data that suggested a functional benefit with combined alteplase and thrombectomy, but also a higher risk of symptomatic intracranial hemorrhage. This difference emphasizes the importance of the route of administration, dose, and timing of alteplase delivery after thrombectomy.
The results of CHOICE2 represent a potentially significant advancement in stroke care. Further research will be crucial to determine which patients are most likely to benefit from this combined approach and to optimize treatment protocols to maximize efficacy and minimize risks. The findings suggest that a two-pronged approach to treating large-vessel occlusion ischemic stroke may improve outcomes for patients who have already undergone successful thrombectomy.
