Nationwide temporal trend analysis of reperfusion therapy utilization and mortality in acute ischemic stroke patients in Japan

Abstract This study aimed to elucidate nationwide trends in reperfusion therapy utilization and subsequent 30-day mortality in acute ischemic stroke patients in Japan. The analysis focused on intravenous recombinant tissue plasminogen activator (IV rt-PA) and endovascular thrombectomy (EVT). Using health insurance claims data, we calculated the age- and sex-adjusted monthly number of acute ischemic stroke patients who received IV rt-PA and/or EVT in Japan from April 2010 to March 2016, and investigated the 30-day all-cause mortality rates after undergoing these therapies. Through an interrupted time-series analysis, we examined the(1) trends prior to extension of the IV rt-PA therapeutic time window from 3 hours to 4.5 hours in September 2012,(2) changes that occurred immediately after the extension, and(3) differences in trends between the pre- and post-extension periods. During the study period, 69,920 patients with acute ischemic stroke (mean age ± standard deviation: 74.9 ± 12.0 years; 41.4% women) received IV rt-PA and/or EVT. The age- and sex-adjusted number of patients receiving IV rt-PA monotherapy increased immediately after the time window extension ( P < .001), but did not change during the pre- (P = .90) and post-extension (P = .58) periods. In contrast, the number of patients receiving EVT with or without IV rt-PA continuously increased during the pre-extension period (P < .001), and further increased during the post-extension period (P <.001); however, this number decreased immediately after the extension (P < .001). There were no significant changes in 30-day all-cause mortality during the pre- (P = .40) and post-extension (P = .64) periods, as well as immediately after the extension (P = .53). The extension of the IV rt-PA therapeutic time window and progressively widespread use of EVT in Japan have increased the number of acute ischemic stroke patients eligible for reperfusion therapy. These trends were not accompanied by a higher risk of post-reperfusion mortality.

[1]  H. Yasunaga,et al.  Expanded Indication for Recombinant Tissue Plasminogen Activator from 3 to 4.5 h after Onset of Stroke in Japan. , 2020, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[2]  D. Liebeskind,et al.  Patterns of Mechanical Thrombectomy for Stroke Before and After the 2015 Pivotal Trials and US National Guideline Update. , 2020, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[3]  Jinkwon Kim,et al.  Characteristics and management of stroke in Korea: 2014–2018 data from Korean Stroke Registry , 2020, International journal of stroke : official journal of the International Stroke Society.

[4]  S. Kiechl,et al.  Trends of r-tPA (Recombinant Tissue-Type Plasminogen Activator) Treatment and Treatment-Influencing Factors in Acute Ischemic Stroke , 2020, Stroke.

[5]  K. Iihara,et al.  Trends in Endovascular Reperfusion Therapy for Acute Stroke after Introduction of Mechanical Thrombectomy Devices: Japanese Registry of NeuroEndovascular Therapy (JR-NET)3 , 2020, Neurologia medico-chirurgica.

[6]  R. Sacco,et al.  Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke. , 2019, Stroke.

[7]  J. Grotta,et al.  Real-World Treatment Trends in Endovascular Stroke Therapy , 2019, Stroke.

[8]  W. Powers,et al.  2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association , 2018, Stroke.

[9]  Eric E. Smith,et al.  Increase in Endovascular Therapy in Get With The Guidelines-Stroke After the Publication of Pivotal Trials , 2017, Circulation.

[10]  J. Saver,et al.  Direct Mechanical Thrombectomy Versus Combined Intravenous and Mechanical Thrombectomy in Large-Artery Anterior Circulation Stroke: A Topical Review , 2017, Stroke.

[11]  G. Peng,et al.  Nationwide “Hospital Emergent Capability Accreditation by Level-Stroke” Improves Stroke Treatment in Taiwan , 2017, Journal of stroke.

[12]  G. Hankey,et al.  Stroke , 2017, The Lancet.

[13]  V. Feigin,et al.  Global Burden of Stroke. , 2017, Circulation research.

[14]  Michael T. Mullen,et al.  Progressive rural–urban disparity in acute stroke care , 2017, Neurology.

[15]  L. Lisabeth,et al.  Emerging temporal trends in tissue plasminogen activator use , 2016, Neurology.

[16]  Eric E. Smith,et al.  Why are acute ischemic stroke patients not receiving IV tPA? , 2016, Neurology.

[17]  Adnan H Siddiqui,et al.  Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis. , 2016, JAMA.

[18]  Hester F. Lingsma,et al.  Increase in national intravenous thrombolysis rates for ischaemic stroke between 2005 and 2012: is bigger better? , 2016, BMC Neurology.

[19]  A. Demchuk,et al.  Endovascular Therapy in Acute Ischemic Stroke: Challenges and Transition From Trials to Bedside. , 2016, Stroke.

[20]  Claudia E. Koller,et al.  How can we improve stroke thrombolysis rates? A review of health system factors and approaches associated with thrombolysis administration rates in acute stroke care , 2015, Implementation Science.

[21]  A. Kim,et al.  Global Stroke Belt: Geographic Variation in Stroke Burden Worldwide , 2015, Stroke.

[22]  A. Meretoja,et al.  Twenty-Year History of the Evolution of Stroke Thrombolysis With Intravenous Alteplase to Reduce Long-Term Disability , 2015, Stroke.

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

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

[25]  Eric E. Smith,et al.  Endovascular Clot Retrieval Therapy: Implications for the Organization of Stroke Systems of Care in North America , 2015, Stroke.

[26]  M. Koga,et al.  Acute reperfusion therapy and stroke care in Asia after successful endovascular trials. , 2015, Stroke.

[27]  Andrew E. Hanselman,et al.  Topical Review , 2015, Foot & ankle specialist.

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

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

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

[31]  Eric E. Smith,et al.  Race/Ethnic Differences in the Risk of Hemorrhagic Complications Among Patients With Ischemic Stroke Receiving Thrombolytic Therapy , 2014, Stroke.

[32]  V. Feigin,et al.  Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010 , 2014, The Lancet.

[33]  Eric E. Smith,et al.  Temporal Trends in Patient Characteristics and Treatment With Intravenous Thrombolysis Among Acute Ischemic Stroke Patients at Get With the Guidelines–Stroke Hospitals , 2013, Circulation. Cardiovascular quality and outcomes.

[34]  W. Powers,et al.  Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association , 2013, Stroke.

[35]  Eric E. Smith,et al.  Use of Tissue-Type Plasminogen Activator Before and After Publication of the European Cooperative Acute Stroke Study III in Get With The Guidelines-Stroke , 2012, Circulation. Cardiovascular quality and outcomes.

[36]  B. Norrving,et al.  Thrombolytic Therapy Rates and Stroke Severity: An Analysis of Data From the Swedish Stroke Register (Riks-Stroke) 2007–2010 , 2012, Stroke.

[37]  J. Wellmann,et al.  Impact of the Extended Thrombolysis Time Window on the Proportion of Recombinant Tissue-Type Plasminogen Activator-Treated Stroke Patients and on Door-to-Needle Time , 2011, Stroke.

[38]  B. Norrving,et al.  Effects of Extending the Time Window of Thrombolysis to 4.5 Hours: Observations in the Swedish Stroke Register (Riks-Stroke) , 2011, Stroke.

[39]  K. H. Åsberg,et al.  Dissemination of Thrombolysis for Acute Ischemic Stroke Across a Nation: Experiences From the Swedish Stroke Register, 2003 to 2008 , 2010, Stroke.

[40]  E. Jauch,et al.  Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. , 2009, Stroke.

[41]  E. Jauch,et al.  Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator: a science advisory from the American Heart Association/American Stroke Association. , 2009, Stroke.

[42]  V. Feigin,et al.  Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review , 2009, The Lancet Neurology.

[43]  Keith Muir,et al.  Thrombolysis with alteplase 3–4·5 h after acute ischaemic stroke (SITS-ISTR): an observational study , 2008, The Lancet.

[44]  M. Kaste,et al.  Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. , 2008, The New England journal of medicine.

[45]  T. Cullen,et al.  Global existence of solutions for the relativistic Boltzmann equation on the flat Robertson-Walker space-time for arbitrarily large intial data , 2005, gr-qc/0507035.

[46]  A K Wagner,et al.  Segmented regression analysis of interrupted time series studies in medication use research , 2002, Journal of clinical pharmacy and therapeutics.

[47]  Koroshetz Wj,et al.  Tissue plasminogen activator for acute ischemic stroke. , 1996, The New England journal of medicine.

[48]  Joseph P. Broderick,et al.  Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. , 1995 .

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

[50]  A. Rabinstein.  Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke , 2009 .

[51]  G. Donnan,et al.  4.5 Hours The New Time Window for Tissue Plasminogen Activator in Stroke , 2009 .

[52]  K. Grimes.  Systems of Care in North America , 2004 .