Clinical Study
Feasibility and outcomes of intravenous thrombolysis 3–4.5 hours after stroke in Chinese patients

https://doi.org/10.1016/j.jocn.2013.08.014Get rights and content

Abstract

The time window for intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment in acute ischemic stroke (AIS) patients has been extended to 4.5 hours. But little is known about the safety and efficacy of IV rt-PA treatment in the 3–4.5 hour time window in Chinese patients with AIS. A total of 119 patients who were treated with standard IV rt-PA therapy within 4.5 hours after symptom onset were included in this study: 85 were treated within 0–3 hours and 34 were treated within 3–4.5 hours. Favorable outcome was defined as a modified Rankin scale (mRS) score of 0–1 at 6 months. The safety of IV rt-PA treatment was assessed by the rate of mortality, symptomatic intracerebral hemorrhage (SICH) and other common complications. There were no significant differences in SICH rates (2.94% versus 2.35%; p = 0.85) at 24–36 hours, mortality (5.88% versus 3.53%; p = 0.56), other complications (14.71% versus 11.76%; p = 0.66), National Institutes of Health Stroke Scale (NIHSS) score improvement at 24 hours (41.18% versus 45.88%; p = 0.64) and favorable mRS at 6 months (52.94% versus 54.12%; p = 0.91) between the two time window groups. Multivariate analysis showed that advanced age, lower admission NIHSS score and shorter time from symptom onset to treatment were associated with a favorable clinical outcome. This finding showed an additional 29% of patients received IV rt-PA because of the treatment window expansion to 4.5 hours. IV rt-PA was feasible and safe for treating AIS patients in the 3–4.5 hour time window in our Chinese population.

Introduction

Stroke, with an annual incidence of 219 people per 100,000 in a population of approximately 1.3 billion, is the second most common cause of death and the leading cause of adult disability in China. Stroke is a heavy burden on the Chinese healthcare system. Acute thrombolytic therapy offers the potential to achieve early recanalization, save tissue, and improve outcome. Currently, intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is the only approved acute stroke therapy. IV rt-PA treatment has been shown to reduce the combined endpoints of death and disability if administered within 3 hours of the onset of acute cerebral ischemia [1]. In 2001, the State Food and Drug Administration of China approved IV rt-PA treatment for acute ischemic stroke (AIS). Nonetheless, only a small proportion of stroke patients present to hospital and receive this treatment within 3 hours of symptom onset in China, partly related to the very narrow therapeutic time window for intervention [2]. In 2008, the outcome of the European Acute Stroke Study III (ECASS III) randomized controlled trial [3] and the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) observational study [4] provided evidence supporting an expansion of the IV rt-PA treatment time window up to 4.5 hours after symptom onset [5]. In May 2009, a science advisory report from the American Stroke Association recommended the use of IV rt-PA for patients presenting within 3 and 4.5 hours after symptom onset [6]. The 2010 Chinese guidelines for the diagnosis and treatment of AIS approved IV rt-PA treatment for AIS within 4.5 hours after the onset of symptoms.

Recent studies demonstrated that patients had a better outcome at 24 hours and 3 months after receiving IV rt-PA within the 4.5 hour time window after stroke [3], [4]. However little is known about the safety and efficacy of IV rt-PA treatment in this extended window in Chinese AIS patients. Sparse data are available on early predictors for favorable outcome in AIS patients at 6 months. We aimed to determine the feasibility and outcome of treatment with IV rt-PA in the 3–4.5 hour time window in Chinese patients with AIS and compared the results with Western studies.

Section snippets

Patients and methods

In this prospective study, we included patients presenting with AIS who were given IV rt-PA within 4.5 hours after symptom onset. This study was approved by the hospital ethics committee on human research. All patients or patient care providers gave written informed consent before thrombolysis. Data regarding demographic characteristics, risk factors, baseline clinical parameters and stroke mechanisms from consecutive patients with AIS were collected prospectively. For all patients, time of

Results

A total of 124 patients who received IV rt-PA treatment within 4.5 hours of symptom onset were included in our initial study. After excluding the patients with missing data (two were missing assessment at 6 months, two were missing time of symptom onset and one was missing time of thrombolysis), 119 patients were included in the current study. Of these, 85 were treated with IV rt-PA within 3 hours and 34 within 3–4.5 hours after symptom onset.

Demographic characteristics, risk factors, baseline

Discussion

The benefits of IV rt-PA in AIS are strongly time-dependent [3]. There has been considerable interest in expanding the time window for administration of IV rt-PA to increase the number of patients who can benefit from thrombolytic treatment [7], [8], [9], [10]. Unlike developed countries, the majority (82.9%) of stroke patients in China arrive at hospital beyond 3 hours after symptom onset [2], [11]. Extending the time window is an important strategy in maximizing thrombolytic therapy in stroke

Conflicts of Interest/Disclosures

The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.

Acknowledgements

The authors would like to thank all participating patients and their families, and the Department of Neurology staff in Wuhan General Hospital of Guangzhou Command for their invaluable assistance.

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