In Canadian meta-analysis that included nearly 1,300 patients with large-vessel ischaemic stroke, earlier treatment with endovascular thrombectomy plus medical therapy, compared with medical therapy alone, was associated with less disability at three months.
Five randomised trials have demonstrated the benefit of second-generation endovascular recanalization therapies over medical therapy alone among patients with acute ischemic stroke due to large vessel occlusions (blockage). However, uncertainties remain about the benefit and risk of endovascular intervention when under taken more than 6 hours after symptom onset.
Dr Michael D Hill, of the University of Calgary, Calgary, Canada, and colleagues conducted a meta-analysis of the data from these 5 randomised trials (1,287 patients enrolled at 89 international sites). Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled.
The researchers found that compared with medical therapy alone, earlier treatment with endovascular thrombectomy plus medical therapy was associated with lower degrees of disability at 3 months. Benefit was greatest with time from symptom onset to arterial puncture for thrombectomy of less than 2 hours and became non-significant after 7.3 hours.
Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favourable degree of disability and less functional independence, but no change in mortality.
The authors note that within 7.3 hours, “functional outcomes were better the sooner after symptom onset that endovascular reperfusion was achieved, emphasising the importance of programmes to enhance patient awareness, out-of-hospital care, and in-hospital management to shorten symptom onset-to-treatment times.”
“The results of this study reinforce guideline recommendations to pursue endovascular treatment when arterial puncture can be initiated within 6 hours of symptom onset, and provide evidence that potentially supports strengthening of recommendations for treatment from 6 through 7.3 hours after symptom onset.”
Importance: Endovascular thrombectomy with second-generation devices is beneficial for patients with ischaemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time with outcomes would help to guide implementation.
Objective: To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage.
Design, Setting, and Patients: Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites.
Exposures: Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment.
Main Outcomes and Measures: The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation.
Results: Among all 1287 patients (endovascular thrombectomy + medical therapy [n = 634]; medical therapy alone [n = 653]) enrolled in the 5 trials (mean age, 66.5 years [SD, 13.1]; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96 to 3.98), absolute risk difference (ARD) for lower disability scores, 39.2%; cOR at 6 hours, 1.98 (95% CI, 1.30 to 3.00), ARD, 30.2%; cOR at 8 hours,1.57 (95% CI, 0.86 to 2.88), ARD, 15.7%; retaining statistical significance through 7 hours and 18 minutes. Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 [95% CI, 0.76 to 0.93]; ARD, −6.7%) and less functional independence (OR, 0.81 [95% CI, 0.71 to 0.92], ARD, −5.2% [95% CI, −8.3% to −2.1%]), but no change in mortality (OR, 1.12 [95% CI, 0.93 to 1.34]; ARD, 1.5% [95% CI, −0.9% to 4.2%]).
Conclusions and Relevance: In this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy + medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months. Benefit became nonsignificant after 7.3 hours.
Jeffrey L Saver; Mayank Goyal; Aad van der Lugt; Bijoy K Menon; Charles BLM Majoie; Diederik W Dippel; Bruce C Campbell; Raul G Nogueira; Andrew M Demchuk; Alejandro Tomasello; Pere Cardona; Thomas G Devlin; Donald F Frei; Richard du Mesnil de Rochemont; Olvert A Berkhemer; Tudor G Jovin; Adnan H Siddiqui; Wim H van Zwam; Stephen M Davis; Carlos Castaño; Biggya L Sapkota; Puck S Fransen; Carlos Molina; Robert J van Oostenbrugge; Ángel Chamorro; Hester Lingsma; Frank L Silver; Geoffrey A Donnan; Ashfaq Shuaib; Scott Brown; Bruce Stouch; Peter J Mitchell; Antoni Davalos; Yvo BWEM Roos; Michael D Hill