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Editor's Note
June 2, 2020

Long-term Outcomes After Thrombolytic Therapy for Acute Ischemic Stroke

Author Affiliations
  • 1Senior Editor, JAMA, Chicago, Illinois
  • 2Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois
JAMA. 2020;323(21):2184-2185. doi:10.1001/jama.2020.5269

The role of intravenous thrombolytic therapy in the management of acute ischemic stroke is well established,1 and faster administration of intravenous tissue plasminogen activator (tPA) has been associated with better short-term outcomes in clinical practice.2

However, it is less certain whether faster time to treatment with thrombolytic therapy is associated with better long-term outcomes, such as long-term survival. Clinical trial data have not demonstrated a long-term mortality benefit with thrombolytic therapy, perhaps because trials were underpowered for this outcome.3 Observational data have demonstrated better long-term survival among patients who were treated with thrombolytic therapy vs those who were not, but reports have not included sufficient detail on process measures to explore the relationship between time to treatment (ie, door-to-needle time) and long-term outcomes.4 In the US, Get With The Guidelines–Stroke (GWTG-Stroke; a nationwide voluntary registry and quality improvement program) contains the granular process measure data needed for such an analysis; however, long-term follow-up data are generally not collected.5

In this issue of JAMA, Man et al6 linked detailed information about time to treatment from the GWTG-Stroke registry with long-term clinical outcomes ascertained using Medicare claims data to evaluate the association between door-to-needle times and 1-year outcomes for more than 61 000 patients with acute ischemic stroke who were treated with intravenous tPA from 2006 to 2016. The study findings demonstrated that longer door-to-needle times, compared with more rapid time to treatment, were significantly associated with a higher risk of all-cause mortality, readmission, and a composite of all-cause mortality or readmission at 1 year, although the absolute differences for some of the outcomes were relatively modest. The analyses were generally consistent whether time was analyzed in 15-minute increments or using recommended treatment targets of door-to-needle times of within 45 minutes vs longer than 45 minutes and within 60 minutes vs longer than 60 minutes.

The large number of patients in the study may have allowed for detection of statistically significant associations, but the data set and the study design have some limitations that may affect the generalizability of the findings. First, because of the linkage to Medicare data for outcome ascertainment, the study population included only older adults, with a median age of 80 years. Second, a large number of individuals (n = 41 195) in the GWTG-Stroke registry were excluded from the study because linkage with Medicare claims data was not possible, including a higher proportion of racial/ethnic minorities. Third, patients who received concomitant therapy with intra-arterial reperfusion techniques were excluded to focus the analysis on patients treated solely with intravenous tPA.

Nonetheless, this study fills an important gap in the literature by convincingly documenting the association between faster treatment with intravenous tPA and better long-term outcomes, including 1-year mortality. The findings are yet another reason for clinicians and health systems to design stroke services that can treat patients with acute ischemic stroke with thrombolytic therapy in a rapid fashion.

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Article Information

Corresponding Author: Christopher C. Muth, MD, JAMA, 330 N Wabash Ave, Chicago, IL 60611 (christopher.muth@jamanetwork.org)

Conflict of Interest Disclosures: None reported.

Powers  WJ, Rabinstein  AA, Ackerson  T,  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: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.   Stroke. 2019;50(12):e344-e418. doi:10.1161/STR.0000000000000211PubMedGoogle ScholarCrossref
Saver  JL, Fonarow  GC, Smith  EE,  et al.  Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke.   JAMA. 2013;309(23):2480-2488. doi:10.1001/jama.2013.6959PubMedGoogle ScholarCrossref
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Muruet  W, Rudd  A, Wolfe  CDA, Douiri  A.  Long-term survival after intravenous thrombolysis for ischemic stroke: a propensity-matched cohort with up to 10-year follow-up.   Stroke. 2018;49(3):607-613. doi:10.1161/STROKEAHA.117.019889PubMedGoogle ScholarCrossref
Ormseth  CH, Sheth  KN, Saver  JL, Fonarow  GC, Schwamm  LH.  The American Heart Association’s Get With the Guidelines (GWTG)-Stroke development and impact on stroke care.   Stroke Vasc Neurol. 2017;2(2):94-105. doi:10.1136/svn-2017-000092PubMedGoogle ScholarCrossref
Man  S, Xian  Y, Holmes  DN,  et al.  Association between thrombolytic door-to-needle time and 1-year mortality and readmission in patients with acute ischemic stroke.   JAMA. doi:10.1001/jama.2020.5697Google Scholar