Standard strategies for acute ischemic stroke within the rtPA therapeutic window

Although considerable progress has been made in developing effective prevention and treatment strategies for acute ischemic stroke (AIS), substantial challenges remain to improve quality of care.1 Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is currently the only evidence-based medical therapy for AIS and was approved by the State Food and Drug Administration of China in 2001. In this commentary, we sought to address the standard therapeutic strategies for AIS within the rtPA therapeutic window and the potential factors that would affect this approach in China.

Standard therapeutic strategies for AIS within rtPA therapeutic window in China

As in other national and international stroke guidelines,2,3 IV thrombolysis is recommended as first-line treatment for AIS within the therapeutic window by the Chinese stroke guideline.4 Although there is much variability for stroke thrombolysis throughout China, some general rules have been followed. Generally, it is highly recommended that patients with AIS should be treated with IV tPA within 4.5 hours or with urokinase within 6 hours of symptom onset in China.5 Intra-arterial thrombolysis (with tPA or urokinase) is an option for treatment of selected patients who have a major stroke of less than 6 hours' duration due to occlusion of middle cerebral artery and who are not otherwise candidates for IV thrombolysis. In addition, intra-arterial thrombolysis could be an option for treatment of selected patients who have a major stroke of less than 24 hours' duration due to large artery occlusion in posterior circulation (such as basilar or vertebral artery) and who are not otherwise candidates for IV thrombolysis. Although the menu available for clinicians and interventionists to reopen occluded arteries has been greatly expanded in recent years, such as IV combination with intra-arterial thrombolysis (bridging fashion), mechanical clot retrieval, and angioplasty and/or stenting, currently these therapies can only be performed in a small number of qualified comprehensive stroke centers in China. Besides neuroimaging examination, some laboratory tests are usually carried out before stroke thrombolysis in China, such as complete blood count (including hematocrit, hemoglobin, platelet count, and white blood cell count), biochemistry tests (including liver function, kidney function, and serum glucose), and coagulation tests (including activated partial thromboplastin time, prothrombin time, international normalized ratio [INR], and fibrinogen). Routinely, head CT is required before tPA administration. If there are signs of neurologic deterioration after tPA administration, head CT will be performed to check for secondary intracranial hemorrhage. The general rules of pre- and post-thrombolysis management (e.g., blood pressure control) are similar to those recommended by American stroke guideline2; however, traditional Chinese medicines for neuroprotection are often used post-thrombolysis in China.

Factors potentially affecting stroke thrombolysis in China

In China, the media, government, and authorities have called the attention of the public and of clinicians to stroke. However, based on data from the China National Stroke Registry (CNSR),6 only 2.4% of AIS patients were treated with either IV or intra-arterial thrombolysis.7 Potential reasons for this dismal record vary and can be classified into the following 4 categories: 1) prehospital delay; 2) in-hospital delay; 3) lack of basic infrastructure; and 4) lack of readiness of treating clinicians or patients/families for stroke thrombolysis treatment.

The results of China’s QUEST study (a prospective, multicenter, hospital-based registry of patients with acute stroke in urban China) showed that the median time from stroke onset to hospital presentation was 15.0 hours (interquartile range, 2.8–51.0 hours).8 Similarly, data from the CNSR indicated that the majority (82.9%) of patients with AIS arrived at hospital beyond 3 hours of symptom onset.6 Based on our experience, there are 2 major factors accountable for long prehospital delay in China: poor public knowledge about stroke (such as inability to recognize stroke signs and symptoms, a wait-and-see attitude, unwillingness to call emergency medical service) and ineffective emergency medical systems to deliver stroke patients to capable hospitals.

Data from the CNSR showed that the median door-to-needle time was 116 minutes.7 Meanwhile, 68.1% of eligible patients failed to receive thrombolysis due to in-hospital delay.7 Long process to obtain written consent, delay in completing laboratory tests, and waiting for patients' families to purchase rtPA (before 2008, IV thrombolysis with rtPA for AIS was not covered by health care insurance) have been identified as major factors associated with in-hospital delay.7 More importantly, lack of standardized and effective clinical pathways for stroke thrombolysis are the fundamental reasons for long in-hospital delay in China.

Hospitals in China are classified into 3 levels according to location, bed number, staff expertise, and facilities. A Level I is a community-based hospital operating in a street or a village with only the basic facilities and very limited inpatient capability; a Level II hospital is a regional hospital operating in a predesigned administrative area with at least 100 inpatient beds providing acute medical care and preventive care services to populations of at least 100,000 people; a Level III hospital is a large hospital serving as a major tertiary reference center in the provincial capitals and major cities with more than 1,000 beds. Currently, stroke thrombolysis is mainly performed in Level III and some Level II hospitals. For many hospitals in China, there is lack of basic infrastructure (technique and personnel) to perform stroke thrombolysis, especially for community hospitals and hospitals in rural areas and underdeveloped regions.

Among a substantial proportion of Chinese physicians, there is excessive fear of adverse effects of stroke thrombolysis (e.g., symptomatic intracranial hemorrhage) and potential relevant litigation, especially by emergency physicians who first see the patients with stroke. When obtaining consent, the treating physician might overemphasize the adverse effects, having a negative impact on patients’ or their families' decision.

Outlook of stroke thrombolysis in China

A nationwide program focusing on improving quality of stroke thrombolysis is going on in China (Multidisciplinary and Organized Stroke Thrombolytic therapy Project [MOST]). In the future, health and medical care promotion strategies to improve community awareness of stroke, expanded availability and utilization of ambulance services, implementation of stroke center certification project, creation of effective clinical pathways for stroke thrombolysis, strengthening professional training on stroke thrombolysis, and establishment of telemedicine service are necessary and promising methods to expedite stroke thrombolysis in China.

Correspondence to: yongjunwang1962@gmail.com