Alteplase after thrombectomy improves neurological outcomes in acute ischemic stroke
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Intra-arterial alteplase after successful reperfusion with mechanical thrombectomy for large vessel occlusion acute ischemic stroke conferred better neurological outcomes compared with placebo, a speaker reported.
Despite the early termination of the trial, the positive results of the CHOICE trial presented at the International Stroke Conference and published in JAMA indicated that intra-arterial alteplase (Activase, Genentech) after successful thrombectomy was associated with more patients achieving a modified Rankin score of 0 or 1 at 90 days after acute ischemic stroke compared with placebo.
“Seventy-one percent of the patients that are treated with mechanical thrombectomy have successful reperfusion, defined as a Thrombolysis in Cerebral Ischemia 2b/3, but the truth is that only 27% of the patients treated with mechanical thrombectomy are disability free at 3 months, defined as a Rankin score of 0 to 1,” Ángel Chamorro, MD, PhD, of the department of neuroscience at the Hospital Clinic of Barcelona, Spain, said during the presentation. “A prevailing interpretation for this suboptimal efficacy is that many of these patients may have irreversible brain damage by the time that reperfusion occurs. We think that this is certainly true, but there are other possibilities. We anticipated that impaired reperfusion of microcirculation despite full reperfusion on serial angiography could be an explanation for the suboptimal efficacy in many patients [who had] mechanical thrombectomy.”
To test this theory, researchers designed the CHOICE trial to evaluate the efficacy and safety of adjunct intra-arterial alteplase compared with placebo in patients with large vessel occlusion acute ischemic stroke treated with mechanical thrombectomy resulting in successful reperfusion.
In March 2020, the researchers were informed that the placebo used in this trial could not be restocked after its shelf-life expiration and the trial was discontinued in February 2021 after enrolling 121 participants, or 60% of the total sample size (mean age, 71 years; 54% men).
Researchers randomly assigned patients with successful reperfusion to alteplase (0.225 mg/kg; maximum dose, 22.5 mg) or placebo. The primary outcome was modified Rankin score of 0 to 1 at 90 days follow-up. The secondary outcome was angiographic improvement, and the safety outcomes were incidence of symptomatic intracranial hemorrhage at 24 hours and 90-day mortality.
The median Alberta Stroke Program Early CT Score (ASPECTS) was 9 for both groups.
At 90 days, more patients in the intra-arterial alteplase arm compared with the placebo arm achieved a modified Rankin score of 0 or 1, with an absolute risk difference of 18.4% (95% CI, 0.3-36.4; P = .047).
According to the presentation, the improvements in modified Rankin score was not explained by improvement on angiography (9% vs. 8%; risk difference = 0.6%; 95% CI, –9.5 to 10.7).
Symptomatic intracranial hemorrhage at 24 hours occurred in 0% of the alteplase arm and 3.8% of the placebo arm (risk difference = –3.9%; 95% CI, –21.2 to 13.4). The occurrence of 90-day mortality was 8% in the alteplase arm compared with 15% in the placebo arm (risk difference = –7.3%; 95% CI, –19.3 to 4.6).
“The adjunct use of intra-arterial alteplase is safe and increases the likelihood of long-term excellent neurological outcome in patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy,” Chamorro said. “The clinical vs. angiographic mismatch encountered in the study stresses the limitations of conventional angiography to monitor these patients and highlights the relevance of the microcirculation to improve the clinical efficacy of mechanical thrombectomy. Since the study was terminated earlier, we want to caution and ask for a CHOICE 2 validation of these findings in order to change clinical practice.”
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Chamorro A. LB6. Presented at: International Stroke Conference; Feb. 9-11, 2022; New Orleans (hybrid meeting).
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