Two Trials Challenge the Limits of Stroke Thrombectomy

Two new randomized trials suggested endovascular thrombectomy (EVT) might benefit a broader range of patients with large-vessel occlusion stroke (LVO) than current recommendations suggest.One trial suggested that EVT might improve functional outcomes in select patients treated 24-72 hours after stroke onset, whereas the other pointed to potential benefits in patients with neurologic deficits. Both studies challenged current treatment boundaries, although the findings underscored the need to weigh potential benefits against safety risks.In the first trial, EVT improved functional outcomes at 90 days compared with standard treatment in patients with anterior-circulation LVO treated 24-72 hours after stroke onset. However, symptomatic intracranial hemorrhage (ICH) and 90-day mortality were more frequent with EVT than with standard medical care alone.In the second trial, EVT increased the likelihood of excellent functional recovery in patients with mild stroke and anterior-circulation LVO treated within 24 hours. EVT also reduced the risk for early neurologic worsening, although serious procedure-related complications occurred in 13.2% of patients.Together, these studies might have helped clarify the role of EVT in patients previously considered outside the usual treatment window or too mildly affected to undergo the procedure.Both papers were published online on October 23 in The New England Journal of Medicine.Expanding Thrombectomy EligibilityLandmark trials established that EVT improves functional outcomes in acute ischemic stroke caused by anterior-circulation LVO. The treatment window later expanded to include select patients treated up to 24 hours after symptom onset. However, the benefits of EVT beyond that window or in patients with mild symptoms remain uncertain.Approximately 10%-20% of patients with mild deficits and LVO experience early neurologic deterioration, which can lead to disability. However, patients treated more than 24 hours after symptom onset may retain salvageable brain tissue, suggesting that they could still benefit from reperfusion.To evaluate whether EVT could help these patients, both trials used perfusion imaging to identify those with a small infarct core and potentially salvageable brain tissue. The study populations also reflected the high prevalence of intracranial atherosclerosis in China.The LATE-MT trial included 336 patients with anterior-circulation LVO who presented 24-72 hours after symptom onset or last known well.Participants at 35 comprehensive stroke centers in China were randomly assigned to EVT plus standard medical care (n = 168; mean age, 64 years; 28.0% women) or standard medical care alone (n = 168; mean age, 63 years; 33.3% women).Eligible patients had a National Institutes of Health Stroke Scale (NIHSS) score of at least 6 and imaging evidence of salvageable brain tissue, including an infarct-core volume of less than 50 mL and a perfusion mismatch ratio of at least 1.8.At 90 days, EVT resulted in better overall functional outcomes than standard medical care alone, as measured by modified Rankin Scale scores (mRS; common odds ratio [OR], 1.74; P = .005). Secondary outcomes also favored EVT, including reduced dependency and improved health-related quality of life.However, any ICH within 7 days occurred in 28.3% of patients receiving EVT vs 5.5% in control individuals. Symptomatic ICH occurred within 48 hours in 4.8% vs 0%. The 90-day mortality rate was also higher with EVT (6.0% vs 1.8%).The investigators suggested that the higher rates of bleeding and death might have been related to brain swelling following reperfusion and greater use of thrombolytics and tirofiban, an antiplatelet, in the EVT group.“Careful judgement is therefore warranted with respect to the balance of the potential benefits and harms of intervening when patients are in the late time window,” the investigators, with first author Pengfei Yang, MD, PhD, Neurovascular Center at Changhai Hospital, Naval Medical University First Affiliated Hospital in Shanghai, China, wrote.Benefits in Mild StrokeThe second trial, MILD-MT, evaluated whether EVT could improve outcomes in patients with mild stroke and anterior-circulation LVO.The trial included 300 patients with mild stroke (NIHSS score less than 6), anterior-circulation LVO, and favorable perfusion imaging, defined by an infarct core of 50 mL or less and a perfusion mismatch of at least 50 mL.Patients were randomly assigned to EVT plus medical management (n = 144; mean age, 68 years; 70.8% men) or medical management alone (n = 156; mean age, 65 years; 77.6% men) at 26 centers. The median baseline NIHSS score was 4.At 90 days, 69.4% of patients receiving EVT achieved an excellent functional outcome, defined as an mRS score of 0 or 1, compared with 50.0% of those receiving medical management alone (OR, 2.32; P < .001). The absolute difference between groups was 19.7 percentage points, corresponding to a number needed to treat of approximately 6.Early neurologic deterioration within 7 days was also less common with EVT (13.9% vs 31.4%). Symptomatic ICH rates were similar between groups (2.1% vs 1.9%), although any ICH was more frequent with EVT (18.9% vs 6.8%). Serious procedure-related complications occurred in 13.2% of patients receiving EVT.Beyond the Usual CandidatesThese research findings highlight the challenge of balancing potential benefits against procedural risks when considering EVT outside of established treatment criteria, wrote Gaultier Marnat, MD, of Bordeaux University Hospital in Bordeaux, France, in an accompanying editorial.Mild strokes caused by LVO should not be underestimated, Marnat wrote. The lower rate of early neurologic deterioration in MILD-MT supports earlier research showing that LVO with initially mild symptoms “is not a benign condition,” he added.However, expanding EVT to more patients requires careful consideration of its risks. Marnat pointed to the higher rates of bleeding events and deaths reported in LATE-MT, along with the serious procedure-related complications in MILD-MT, underscoring the importance of identifying patients most likely to benefit.He also raised concerns that antithrombotic medications, including tirofiban and heparin, might have contributed to the increased risk for bleeding in LATE-MT. More than 10% of participants received intravenous thrombolysis, and most received anticoagulant or antithrombotic therapy within 24 hours after randomization.Despite these concerns, Marnat concluded that the overall benefit-risk balance appeared to favor EVT for acute LVO.Ongoing studies, including MOSTE and SELECT LATE, might help refine patient selection and determine whether thrombectomy can safely benefit more patients.Disclosure information for study authors is available in the original study publications. Marnat reported receiving fees from Johnson & Johnson, Medtronic, MicroVention, Penumbra, and Stryker.