Healthy Life-Year Costs of Treatment Speed from Arrival to Endovascular Thrombectomy in Patients with Ischemic Stroke: A Meta-analysis of Individual Patient Data from 7 Randomized Clinical Trials

Mohammed A. Almekhlafi*, Mayank Goyal, Diederik W.J. Dippel, Charles B.L.M. Majoie, Bruce C.V. Campbell, Keith W. Muir, Andrew M. Demchuk, Serge Bracard, Francis Guillemin, Tudor G. Jovin, Peter Mitchell, Philip White, Michael D. Hill, Scott Brown, Jeffrey L. Saver

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)

Abstract

Importance: The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. Objective: To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). Data Sources: PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020. Study Selection: All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included. Data Extraction/Synthesis: Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. Main Outcomes and Measures: Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. Results: Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ≤4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P <.001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. Conclusions and Relevance: In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times..

Original languageEnglish
Pages (from-to)709-717
Number of pages9
JournalJAMA Neurology
Volume78
Issue number6
DOIs
Publication statusPublished - Jun 2021

Bibliographical note

Funding Information:
grants from AngioCare BV, grants from Covidien/ EV3, grants from MEDAC Gmbh/LAMEPRO, grants from Penumbra Inc, grants from Top Medical/ Concentric, grants from Stryker, grants from Stryker European Operations BV, grants from Medtronic, and grants from Thrombolytic Science, LLC, all unrestricted, paid to institution outside the submitted work. Dr Majoie reported grants from CVON/Dutch Heart Foundation paid to institution, grants from European Commission paid to institution, grants from Dutch Health Evaluation Program paid to institution, grants from Stryker paid to institution, and grants from TWIN Foundation paid to institution outside the submitted work; and being a shareholder of Nico-lab. Dr Muir reported receiving nonfinancial support from Boehringer Ingelheim, personal fees from Biogen, personal fees from Bayer, personal fees from AbbVie, personal fees from ReNeuron, and personal fees from Daiichi Sankyo outside the submitted work. Dr Demchuk reported receiving an unrestricted grant from Medtronic for the ESCAPE trial and honoraria from Medtronic for CME events during the conduct of the study and Circle NVI stock ownership outside the submitted work; in addition, Dr Demchuk received a patent for Circle NVI–issued stroke imaging software. Dr Jovin reported being an investor/advisor for Anaconda. Route92, Methinks, Viz.ai, and FreeOx, other support from Corindus Advisor, personal fees from Contego for serving on a medical screening committee, personal fees from Cerenovus for serving on a data safety and monitoring board and a steering committee, grants from Stryker for AURORA, DAWN, grants from Medtronic for REACT, and nonfinancial support from Fundacio Ictus for RACECAT/REVASCAT–related travel outside the submitted work. Dr Mitchell reported receiving institutional research support from Stryker and institutional research support from Medtronic outside the submitted work. Dr White reported an unrestricted educational grant to institution from Stryker, an unrestricted educational grant to institution from Penumbra, an unrestricted educational grant to institution from Medtronic, grants from Microvention, and personal fees from Microvention outside the submitted work. Dr Hill reported a grant from Medtronic LLC to the University of Calgary for the HERMES Collaboration during the conduct of the study; a grant from NoNO Inc to the University of Calgary, a grant from Boehringer Ingelheim Canada to the University of Calgary, and a grant from Biogen Inc to the University of Calgary outside the submitted work; in addition, Dr Hill received a patent for US Patent Office Number 62/086,077 licensed to Circle NVI; and is a director of the Canadian Federation of Neurological Sciences, a not-for-profit group, is a director of the Canadian Stroke Consortium, a not-for-profit group, is a director of Circle NeuroVascular Inc., and has received grant support from Alberta Innovates Health Solutions, CIHR, Heart & Stroke Foundation of Canada, and National Institutes of Neurological Disorders and Stroke. Dr Brown reported receiving personal fees from University of Calgary HERMES for statistical consulting during the conduct of the study; personal fees from Medtronic for statistical consulting outside the submitted work. Dr Saver reported receiving personal fees from Medtronic for contracted hourly payments and travel reimbursement for service on trial steering committee(s), making recommendations regarding

Funding Information:
reported being a member of the scientific advisory board of Palmera Medical, Inc. Dr Goyal reported receiving grants from Medtronic during the conduct of the study, personal fees from Mentice Consulting on acute stroke workflow, personal fees from Medtronic Consulting on acute stroke intervention, personal fees from Microvention for advice on acute stroke intervention, and personal fees from Stryker for advice on acute stroke products outside the submitted work. Dr Dippel reported receiving grants from Dutch Heart Foundation, grants from Brain Foundation Netherlands, grants from The Netherlands Organisation for Health Research and Development, grants from Health Holland Top Sector Life Sciences & Health all paid to institution,

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