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

Abstract

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.

CT-based intravenous thrombolysis 3-4·5 hours after acute ischemic stroke in clinical practice

“…These findings are in accordance with the results of two prospective observational studies examining the routine clinical use of IV alteplase from 181 to 270 minutes after stroke onset, the Safe Implementation of Treatments in Stroke -International Stroke Thrombolysis Registry (SITS-ISTR), 8 and a Dutch single-center study. 9 In contrast, the rate of sICH causing a neurological impairment of ≥4 points on the NIHSS within 48 hours after IVT was lower in the present late group than in ECASS III, SITS-ISTR and the aforementioned Dutch study (Table 3). Risk factors for the development of sICH are older age, 10 history of diabetes, 11 current smoking, 12 stroke severity assessed by the NIHSS score, 13,14 presence and extent of ischemic changes on CCT, 15 high baseline serum glucose, 11 and admission fibrinolytic profile.…”

“…18 Age did not differ between the aforementioned 3 studies and the present investigation (Table 3). Baseline NIHSS scores were highest in the Dutch study and SITS-ISTR, 8,9 lower in ECASS III, 5 and the lowest in the present study. Thus, the high number of patients with a favorable outcome in this study compared to ECASS III, SITS-ISTR and the Dutch study probably results from differences in stroke severity at baseline.…”

“…Our results are in accordance with those of the Dutch study as their patients were also selected with CCT alone. 9 These findings are important for daily clinical routine management of stroke patients who are candidates for IVT in the 3 to 4.5 hours time window. They suggest that (1) CCT alone is sufficient for assessing most patients with acute ischemic stroke, and (2) the evaluation of the ischemic penumbra with MRI or CT, which is not available in most centers on a 24 hour basis, is not mandatory.…”

“…8 In our multivariate analysis based on 394 patients, baseline NIHSS score was an independent predictor of mortality, which is in accordance with the results of the Dutch study. 9 ECASS III, 5 two meta-analyses, 2,17 and SITS-ISTR did not report predictors of mortality. 8 In addition, age and sICH were independent predictors of mortality in this series, which is in accordance with the literature.…”

“…2 In contrast, the present, the SITS-ISTR and the Dutch investigators found no similar correlation. 8,9 The lower number of included patients and the absence of patients who underwent IVT between 4.5 and 6…”