Recombinant Tissue-Type Plasminogen Activator (Alteplase) for Ischemic Stroke 3 to 5 Hours After Symptom Onset

Clark, Wayne M.; Wissman, Stanley; Albers, Gregory W.; Jhamandas, Jack H.; Madden, Kenneth P.; Hamilton, Scott

doi:10.1001/jama.282.21.2019

Cited by 1,031 publications

(336 citation statements)

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“…We found no difference in the occurrence of SICH and early in-hospital mortality between the sub-3 h and 3-4.5 h groups. We observed a similar incidence of SICH (5.7%) and early in-hospital mortality (9.7%) in thrombolysis up to 4.5 h as were reported in the NINDS study [1] and other t-PA registries [7,[12][13][14][15][16][17][18][19], where most patients were treated within 3 h. In the ATLANTIS trial [4], 7.0% of the t-PA treated patients in the 3-5 h time window had a SICH, compared to 5.3% in our cohort.…”

Section: Discussionsupporting

confidence: 82%

“…Two other trials with intravenous t-PA, the European Cooperative Acute Stroke Study (ECASS)-I and ECASS-II [2,3], which had a time window of 6 h, yielded less convincing results. The Alteplase ThromboLysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) trial [4], failed to show a beneficial effect of t-PA administration within a 3-5 h time window.…”

Section: Introductionmentioning

confidence: 99%

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Safety of routine IV thrombolysis between 3 and 4.5 h after ischemic stroke

Uyttenboogaart

Vroomen

Stewart

et al. 2007

Journal of the Neurological Sciences

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Background: The administration of tissue plasminogen activator (t-PA) has been proven effective for ischemic stroke within 3 h after onset. A pooled-analysis of six trials showed that intravenous t-PA still improves outcome when given between 3 to 4.5 h after stroke onset. On the basis of this pooled analysis, t-PA was also routinely offered to our patients between 3-4.5 h. We report the safety and clinical features of this group together with the features of the group given t-PA within 3 h. Methods: Prospectively patient characteristics, stroke severity, stroke subtype, incidence of symptomatic intracerebral hemorrhage (SICH), in-hospital mortality, and 3-months modified Rankin Scale scores (mRS) were registered. Data was analyzed separately for patients treated within 3 h (early group) and those treated between 3-4.5 h (late group). Results: Among 176 patients who underwent intravenous thrombolysis, 101 were treated in the early group and 75 in the late group. Six (5.9%; 95% CI 2.8%-12.3%) patients in the early group and 4 (5.3%; 95% CI 2.2%-12.9%) in the late group developed SICH (p = 1.0). In the early group 13 (12.9%; 95% CI 7.7%-20.8%) patients died within 7 days after admission, compared to 5 (6.7%; 95% CI 3.0%-14.7%) in the late group (p = 0.179). In the early group 44 (43.6%; 95% CI 43.3%-53.3%) were independent (mRS ≤ 2) at three months, compared to 36 (48.0%; 95% CI 37.0%-59.1%) in the late group (p = 0.559). Conclusion: Our data show no trend of decreased safety of thrombolysis beyond 3 h. Due to a small sample size a harmful effect cannot be excluded but seems unlikely.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Safety of routine IV thrombolysis between 3 and 4.5 h after ischemic stroke

Uyttenboogaart

Vroomen

Stewart

et al. 2007

Journal of the Neurological Sciences

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“…IVT therapy was approved by the FDA in 1995. This result was subsequently confirmed by other studies, leading to an extension of the therapeutic window to 4.5 h [12][13][14][15].…”

Section: Introductionsupporting

confidence: 81%

Statement of ESMINT and ESNR regarding recent trials evaluating the endovascular treatment at the acute stage of ischemic stroke

et al. 2013

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“…The ATLANTIS Trial, 23 conducted between December 1993 and July 1998 in 140 university and community hospitals in North America, included 613 patients (ITT population) with a mean baseline NIHSS score of 11. The target population of 547 patients, enrolled between 3 and 5 hours of symptom onset, were randomized to receive 0.9 mg/kg of rt-PA (n ϭ 272) or placebo (n ϭ 275).…”

Section: Atlantismentioning

confidence: 99%

Lessons learned from multicenter randomized clinical trials with intravenous thrombolysis for acute ischemic stroke

Lewandowski

Lotfipour

2002

Journal of Stroke and Cerebrovascular Diseases

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The idea of thrombolysis for acute ischemic stroke dates back to the 1950s. Many different drugs, dosages, routes of administration, and times to treatment have been investigated through the 1980s. This experience led to the recent large randomized trials of intravenous thrombolysis completed in the 1990s, the decade of the brain. Three of the trials used streptokinase, and four trials used recombinant tissue plasminogen activator (rt-PA). In this review, we examine these seven randomized intravenous acute ischemic stroke treatment trials, summarize their results, and draw lessons that might be useful for patient care and in future trials.

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Recombinant Tissue-Type Plasminogen Activator (Alteplase) for Ischemic Stroke 3 to 5 Hours After Symptom Onset

Abstract: This study found no significant rt-PA benefit on the 90-day efficacy end points in patients treated between 3 and 5 hours. The risk of symptomatic ICH increased with rt-PA treatment. These results do not support the use of intravenous rt-PA for stroke treatment beyond 3 hours.

Cited by 1,031 publications

References 11 publications

Safety of routine IV thrombolysis between 3 and 4.5 h after ischemic stroke

Safety of routine IV thrombolysis between 3 and 4.5 h after ischemic stroke

Statement of ESMINT and ESNR regarding recent trials evaluating the endovascular treatment at the acute stage of ischemic stroke

Lessons learned from multicenter randomized clinical trials with intravenous thrombolysis for acute ischemic stroke

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