Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis

Jeffrey L. Saver, Mayank Goyal, Aad van der Lugt, Bijoy K. Menon, Charles B. L. M. 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 CastaoBiggya L. Sapkota, Puck S. Fransen, Carlos Molina, Robert J. van Oostenbrugge, Angel Chamorro, Hester Lingsma, Frank L. Silver, Geoffrey A. Donnan, Ashfaq Shuaib, Scott Brown, Bruce Stouch, Peter J. Mitchell, Antoni Davalos, B. W. E. M. Roos, Michael D. Hill*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1114 Citations (Web of Science)

Abstract

IMPORTANCE Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic 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.
Original languageEnglish
Pages (from-to)1279-1288
JournalJAMA-Journal of the American Medical Association
Volume316
Issue number12
DOIs
Publication statusPublished - 27 Sep 2016

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