Reduced Impact of Endovascular Thrombectomy on Disability in Real-World Practice, Relative to Randomized Controlled Trial Evidence in Australia

Background and Aims: Disability-adjusted life years (DALYs) are an important measure of the global burden of disease that informs patient outcomes and policy decision-making. Our study aimed to compare the DALYs saved by endovascular thrombectomy (EVT) in the Australasian-based EXTEND-IA trial vs. clinical registry data from EVT in Australian routine clinical practice. Methods: The 3-month modified Rankin scale (mRS) outcome and treatment status of consecutively enrolled Australian patients with large vessel occlusion (LVO) stroke were taken from the International Stroke Perfusion Imaging Registry (INSPIRE). DALYs were calculated as the summation of years of life lost (YLL) due to premature death and years lived with a disability (YLD). A generalized linear model (GLM) with gamma family and log link was used to compare the difference in DALYs for patients receiving/not receiving EVT while controlling for key covariates. Ordered logit regression model was utilized to compare the difference in functional outcome at 3 months between the treatment groups. Cox regression analysis was undertaken to compare the difference in survival over an 18-year time horizon. Estimated long-term DALYs saved based on the EXTEND-IA randomized controlled trial (RCT) results were used as the comparator. Results: INSPIRE patients who received EVT treatment only achieved nominally better functional outcomes than the non-EVT group (p = 0.181) at 3 months. There was no significant survival gain from EVT over the first 3 months of stroke in both INSPIRE and EXTEND-IA patients. However, measured against no EVT in the long-term, EVT in INSPIRE was associated with no significant survival gain [hazard ratio (HR): 0.92, 95% confidence interval (CI): 0.78–1.08, p = 0.287] compared with the survival benefit extrapolated from the EXTEND-IA trial (HR: 0.42, 95% CI: 0.22–0.82, p = 0.01]. Offering EVT to patients with LVO stroke was also associated with fewer DALYs lost (11.04, 95% CI: 10.45–11.62) than those not receiving EVT in INSPIRE (12.13, 95% CI: 11.75–12.51), a reduction of −1.09 DALY (95% CI: −1.76 to −0.43, p = 0.002). The absolute magnitude of the treatment effect was lower than that seen in EXTEND-IA (−2.72 DALY reduction in EVT vs non-EVT patients). Conclusions: EVT for the treatment of LVO in a registry of routine care was associated with significantly lower DALYs lost than medical care alone, but the saved DALYs are less than those reported in clinical trials, as there were major differences in the baseline characteristics of the patients.

[1]  R. Nogueira,et al.  Large Vessel Occlusion Strokes After the DIRECT-MT and SKIP Trials , 2020, Stroke.

[2]  Ravensara S. Travillian,et al.  Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019 , 2020, The Lancet.

[3]  Y. Zhou,et al.  Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. , 2020, The New England journal of medicine.

[4]  Mary G. George Risk Factors for Ischemic Stroke in Younger Adults , 2020, Stroke.

[5]  Fares Alahdab,et al.  Global, regional, and national burden of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016 , 2019, The Lancet Neurology.

[6]  T. Ueda,et al.  The randomized study of endovascular therapy with versus without intravenous tissue plasminogen activator in acute stroke with ICA and M1 occlusion (SKIP study) , 2019, International journal of stroke : official journal of the International Stroke Society.

[7]  P. Rothwell,et al.  Ordinal vs dichotomous analyses of modified Rankin Scale, 5-year outcome, and cost of stroke , 2018, Neurology.

[8]  W. Feng,et al.  Thrombectomy for acute ischemic stroke in the elderly: a ‘real world’ experience , 2018, Journal of NeuroInterventional Surgery.

[9]  C. Levi,et al.  Correction for Delay and Dispersion Results in More Accurate Cerebral Blood Flow Ischemic Core Measurement in Acute Stroke , 2018, Stroke.

[10]  Geoffrey A. Donnan,et al.  Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost , 2017, Front. Neurol..

[11]  A. Demchuk,et al.  Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials , 2016, The Lancet.

[12]  H. Diener,et al.  Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. , 2015, The New England journal of medicine.

[13]  A. Demchuk,et al.  Thrombectomy within 8 hours after symptom onset in ischemic stroke. , 2015, The New England journal of medicine.

[14]  M. Krause,et al.  Endovascular therapy for ischemic stroke with perfusion-imaging selection. , 2015, The New England journal of medicine.

[15]  Eric E. Smith,et al.  Randomized assessment of rapid endovascular treatment of ischemic stroke. , 2015, The New England journal of medicine.

[16]  D. Smajlović,et al.  Strokes in young adults: epidemiology and prevention , 2015, Vascular health and risk management.

[17]  Hester F. Lingsma,et al.  A randomized trial of intraarterial treatment for acute ischemic stroke. , 2015, The New England journal of medicine.

[18]  K. Furie,et al.  Prognosis of untreated strokes due to anterior circulation proximal intracranial arterial occlusions detected by use of computed tomography angiography. , 2014, JAMA neurology.

[19]  M. Elkind,et al.  The Growing Problem of Stroke among Young Adults , 2013, Current Cardiology Reports.

[20]  C. Levi,et al.  Perfusion CT in acute stroke: a comprehensive analysis of infarct and penumbra. , 2013, Radiology.

[21]  Bernadette A. Thomas,et al.  Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010 , 2012, The Lancet.

[22]  J. Saver,et al.  Years of Disability-Adjusted Life Gained as a Result of Thrombolytic Therapy for Acute Ischemic Stroke , 2010, Stroke.

[23]  Jeffrey L Saver,et al.  Quantifying the Value of Stroke Disability Outcomes: WHO Global Burden of Disease Project Disability Weights for Each Level of the Modified Rankin Scale , 2009, Stroke.

[24]  R. Higashida,et al.  Trial Design and Reporting Standards for Intra-Arterial Cerebral Thrombolysis for Acute Ischemic Stroke , 2003, Stroke.

[25]  W. Manning,et al.  Estimating Log Models: To Transform or Not to Transform? , 1999, Journal of health economics.

[26]  H. B. Mann,et al.  On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other , 1947 .

[27]  F. Sallustio,et al.  Thrombectomy within 8 hours after symptom onset in ischemic stroke , 2015 .