But door-to needle times not consistently associated with stroke recurrence

Shorter door-to-needle times to administer intravenous tissue plasminogen activator (tPA) in acute ischemic stroke were associated with lower mortality and readmission at one year, a retrospective study of Medicare beneficiaries found.

Stroke patients with tPA door-to-needle times longer than 45 minutes had significantly higher:

  • All-cause mortality (35.0% versus 30.8%; HR 1.13; 95% CI, 1.09-1.18).
  • All-cause readmission (40.8% versus 38.4%; HR, 1.08, 95% CI 1.05-1.12).
  • All-cause mortality or readmission (56.0% versus 52.1%; HR 1.09, 95% CI 1.06-1.12).

Until 90 minutes, each 15-minute increase in door-to-needle time was significantly associated with higher all-cause mortality (HR per 15-minute increase in time 1.04) and all-cause admission (HR per 15-minute increase in time 1.02), reported Gregg Fonarow, MD, of University of California Los Angeles, and coauthors.

“Among patients aged 65 years or older with acute ischemic stroke who were treated with tissue plasminogen activator, shorter door-to-needle times were associated with lower all-cause mortality and lower all-cause readmission at 1 year. These findings support efforts to shorten time to thrombolytic therapy,” Fonarow and colleagues wrote in JAMA.

“A door-to-needle time within 30 minutes was not associated with even better outcomes,” they added. “This lack of association needs to be further investigated, although the analyses may be underpowered for this group (5.6% of total patients). Door-to needle times were not consistently associated with recurrent stroke readmission, which is in line with trial results finding no effect of tPA administration on stroke recurrence.”

In an accompanying editorial, Christopher C. Muth, MD, of Rush University Medical Center in Chicago, noted that the 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,” he wrote. “The absolute differences for some of the outcomes were relatively modest.”

Faster tPA administration has been associated with better short-term outcomes in clinical practice, but its effect on longer term outcome is less studied. An intention-to-treat analysis on 624 patients published in 1999 found that those treated with tPA versus placebo within three hours of symptom onset were at least 30% more likely to have no or minimal 12 month disability with no difference in mortality and similar recurrent stroke rates, though the study may have been underpowered to detect differences in these areas. A 2018 study showed increased survival for those given tPA of 5.72 years versus 4.56 years, with 37% reduced 10-year mortality risk, but did not have the resolution to address more detailed door-to-needle time.

For increased resolution in stroke care process data, Fonarow and colleagues turned to the Get With The Guidelines–Stroke registry (GWTG-Stroke), a nationwide voluntary registry and quality improvement program established in 2003, and linked it to 12-month outcomes in Medicare claims data.

They included Medicare beneficiaries age 65 years or older who were treated with intravenous (IV) tPA for acute ischemic stroke between January 2006 and December 2016 within 4.5 hours from the time they were last known to be well. Recurrent stroke, a secondary outcome, was defined as readmission for transient ischemic attack, ischemic and hemorrhagic stroke, carotid endarterectomy or stenting, but not for complications of the index stroke.

In this study, median door-to-needle time was 65 minutes. There were 61,426 patients with door-to-tPA-needle time of 45 minutes or less and 48,666 patients with longer door-to-tPA-needle time.

The 34,367 patients (55.9%) who were treated with tPA and had door-to-needle times of longer than 60 minutes, compared with those treated within 60 minutes, had significantly higher:

  • All-cause mortality (35.8% versus 32.1%; HR 1.11, 95% CI 1.07-1.14).
  • All-cause readmission (41.3% versus 39.1%; HR 1.07, 95% CI 1.04-1.10).
  • All-cause mortality or readmission (56.8% versus 53.1%; HR 1.08, 95% CI 1.05-1.10).

The group with door-to-needle times of greater than 45 minutes did not have significantly higher recurrent stroke readmission (9.3% versus 8.8%; HR 1.05, 95% CI 0.98-1.12).

“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,” Muth noted.

He pointed to the median age of 80 in the study, a consequence of using Medicare data for outcomes, along with the exclusion of potential participants from the GWTG-Stroke registry due to absence of Medicare claims data, and the exclusion of a higher proportion of racial and ethnic minorities. In addition, intra-arterial reperfusion techniques were not included in the study.

  1. Shorter door-to-needle times to administer intravenous tissue plasminogen activator (tPA) in acute ischemic stroke were associated with lower mortality and readmission at one year, a retrospective study of Medicare beneficiaries found.

  2. Door-to needle times were not consistently associated with recurrent stroke readmission.

Paul Smyth, MD, Contributing Writer, BreakingMED™

The Get With The Guidelines–Stroke (GWTG-Stroke) program is provided by the American Heart Association/American Stroke Association. GWTG-Stroke is sponsored, in part, by Novartis, Boehringer Ingelheim Lilly, Novo Nordisk, Sanofi, AstraZeneca, and Bayer.

Fonarow reported receiving research support from the Patient-Centered Outcomes Research Institute and the National Institutes of Health; and being an employee of the University of California, which holds a patent on an endovascular device for stroke.

Fonarow is associate editor of JAMA Cardiology.

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