Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) Collaboration.

Importance: Symptomatic intracranial hemorrhage (sICH) is a serious complication of stroke thrombolytic therapy. Many stroke centers have adopted 0.25-mg/kg tenecteplase instead of alteplase for stroke thrombolysis based on evidence from randomized comparisons to alteplase as well as for its practical advantages. There have been no significant differences in symptomatic intracranial hemorrhage (sICH) reported from randomized clinical trials or published case series for the 0.25-mg/Kg dose. Objective: To assess the risk of sICH following ischemic stroke in patients treated with tenecteplase compared to those treated with alteplase. Design, Setting, and Participants: This was a retrospective observational study using data from the large multicenter international Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) collaboration comprising deidentified data on patients with ischemic stroke treated with intravenous thrombolysis. Data from more than 100 hospitals in New Zealand, Australia, and the US that used alteplase or tenecteplase for patients treated between July 1, 2018, and June 30, 2021, were included for analysis. Participating centers included a mix of nonthrombectomy- and thrombectomy-capacity comprehensive stroke centers. Standardized data were abstracted and harmonized from local or regional clinical registries. Consecutive patients with acute ischemic stroke who were considered eligible and received thrombolysis at the participating stroke registries during the study period were included. All 9238 patients who received thrombolysis were included in this retrospective analysis. Main Outcomes and Measures: sICH was defined as clinical worsening of at least 4 points on the National Institutes of Health Stroke Scale (NIHSS), attributed to parenchymal hematoma, subarachnoid, or intraventricular hemorrhage. Differences between tenecteplase and alteplase in the risk of sICH were assessed using logistic regression, adjusted for age, sex, NIHSS score, and thrombectomy. Results: Of the 9238 patients included in the analysis, the median (IQR) age was 71 (59-80) years, and 4449 patients (48%) were female. Tenecteplase was administered to 1925 patients. The tenecteplase group was older (median [IQR], 73 [61-81] years vs 70 [58-80] years; P < .001), more likely to be male (1034 of 7313 [54%] vs 3755 of 1925 [51%]; P < .01), had higher NIHSS scores (median [IQR], 9 [5-17] vs 7 [4-14]; P < .001), and more frequently underwent endovascular thrombectomy (38% vs 20%; P < .001). The proportion of patients with sICH was 1.8% for tenecteplase and 3.6% for alteplase (P < .001), with an adjusted odds ratio (aOR) of 0.42 (95% CI, 0.30-0.58; P < .01). Similar results were observed in both thrombectomy and nonthrombectomy subgroups. Conclusions and Relevance: In this large study, ischemic stroke treatment with 0.25-mg/kg tenecteplase was associated with lower odds of sICH than treatment with alteplase. The results provide evidence supporting the safety of tenecteplase for stroke thrombolysis in real-world clinical practice.

Racial Disparity in Mechanical Thrombectomy Utilization: Multicenter Registry Results From 2016 to 2020.

Background Previous studies on racial disparity in mechanical thrombectomy (MT) treatment of acute large vessel occlusion stroke lack individual patient data that influence treatment decision-making. We assessed patient-level data in a large US health care system from 2016 to 2020 for racial disparities in MT utilization and eligibility. Methods and Results A retrospective study was performed of 34 596 patients admitted to 43 hospitals from January 2016 to September 2020. Data included patient age, sex, race, residential zip code median income and population density, presenting hospital stroke certification, baseline ambulation, and National Institutes of Health stroke scale. The cohort included 26 640 White, non-Hispanic (77.0%), and 7956 African American/Black (23.0%) patients. In multivariable logistic regression, Black patients were less likely to undergo MT (adjusted odds ratio [OR], 0.65; 95% CI, 0.54-0.76), arrive within 5 hours of "last known well" (adjusted OR, 0.73; 95% CI, 0.69-0.78), and have documented anterior circulation large vessel occlusion (adjusted OR, 0.78; 95% CI, 0.64-0.96). Race was not associated with MT rate among patients arriving within 5 hours of last known well with documented acute large vessel occlusion. Conclusions Black patients with stroke underwent MT less frequently than White patients, likely in part because of longer times from last known well to hospital arrival and a lower rate of documented acute large vessel occlusion. Further studies are needed to assess whether extending the MT time window and more aggressive large vessel occlusion screening protocols mitigate this disparity.

Ceribell EEG shortens seizure diagnosis and workforce time and is useful for COVID isolation.

OBJECTIVE: To determine whether the portable Ceribell® electroencephalograph (EEG) (Mountain View, CA) used for suspected status epilepticus (SE) can reduce time to diagnosis and on-call workforce demands and whether it can be applied to patients in respiratory isolation. METHODS: A multidisciplinary team developed a protocol for the use of the Ceribell EEG. The staff deploying the device, the attending physician, and the interpreting neurologist completed evaluation tools for each patient. Data maintained for quality and resource planning of 18-channel electroencephalography ordered for suspected SE were used as controls. Times to diagnosis were compared by application of Welch-Satterthwaite tests and workforce call-in demands by Fisher's exact t test. We evaluated qualitative data related to the use of the EEG in COVID-19 isolation rooms and on its technical aspects and acceptance by staff members. RESULTS: The Ceribell EEG reduced diagnosis time (P = .0000006) and on-call workforce demand (P = .02). The device can be used at any time of day in any hospital care area and has advantages in respiratory isolation rooms. SIGNIFICANCE: Compared with a standard 18-channel EEG, the Ceribell device allowed earlier diagnosis of SE and non-SE conditions and reduced workforce demands. Due to the ease of its use and its simple components, which can be readily disinfected, it is advantageous for COVID-19 patients in isolation.

Patient Characteristics and Outcomes Associated with Decline in Stroke Volumes During the Early COVID-19 Pandemic.

BACKGROUND AND PURPOSE: Delayed evaluation of stroke may contribute to COVID-19 pandemic-related morbidity and mortality. This study evaluated patient characteristics, process measures and outcomes associated with the decline in stroke presentation during the early pandemic. METHODS: Volumes of stroke presentations, intravenous thrombolytic administrations, and mechanical thrombectomies from 52 hospitals from January 1-June 30, 2020 were analyzed with piecewise linear regression and linear spline models. Univariate analysis compared pandemic (case) and pre-pandemic (control) groups defined in relation to the nadir of daily strokes during the study period. Significantly different patient characteristics were further evaluated with logistic regression, and significantly different process measures and outcomes were re-analyzed after propensity score matching. RESULTS: Analysis of 7,389 patients found daily stroke volumes decreased 0.91/day from March 12-26 (p < 0.0001), reaching a nadir 35.0% less than expected, and increased 0.15 strokes/day from March 27-June 23, 2020 (p < 0.0001). Intravenous thrombolytic administrations decreased 3.3/week from February 19-March 31 (p = 0.0023), reaching a nadir 33.4% less than expected, and increased 1.4 administrations/week from April 1-June 23 (p < 0.0001). Mechanical thrombectomy volumes decreased by 1.5/week from February 19-March 31, 2020 (p = 0.0039), reaching a nadir 11.3% less than expected. The pandemic group was more likely to ambulate independently at baseline (p = 0.02, OR = 1.60, 95% CI = 1.08-2.42), and less likely to present with mild stroke symptoms (NIH Stroke Scale ≤ 5; p = 0.04, OR = 1.01, 95% CI = 1.00-1.02). Process measures and outcomes of each group did not differ, including door-to-needle time, door-to-puncture time, and successful mechanical thrombectomy rate. CONCLUSION: Stroke presentations and acute interventions decreased during the early COVID-19 pandemic, at least in part due to patients with lower baseline functional status and milder symptoms not seeking medical care. Public health messaging and initiatives should target these populations.

Diagnosing deep cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) is a relatively rare vascular disorder involving the formation of a thrombus in the venous system of the cerebral vasculature. The nonspecificity of clinical symptoms seen with CVT elicits significant diagnostic challenges with the potential of serious morbidity and mortality associated with delays in therapeutic intervention. We present a case of CVT in a young patient who presented with loss of consciousness with no headache or focal deficits, the usual type of presentation.

A regional system of stroke care provides thrombolytic outcomes comparable with the NINDS stroke trial.

STUDY OBJECTIVE: Administration of tissue plasminogen activator (tPA) for acute ischemic stroke remains controversial in community practice. Well-organized hierarchic systems of acute stroke care have been proposed to link community hospitals to comprehensive stroke centers. We report safety and functional outcomes in patients treated with tPA in our regional emergency stroke network and compare them with results reported from the trial conducted by the National Institute of Neurological Disorders and Stroke (NINDS). METHODS: Through a statewide communications and transport network, our brain attack center gives emergency medicine staff in the state and surrounding area immediate access to stroke specialists. The team provides consultation about the administration of tPA for ischemic stroke, using the NINDS protocol. Consultations, treatment, and outcomes are documented in our database. RESULTS: From 1996 to 2005, the brain attack center completed 2,670 consultations and diagnosed 1,788 patients with ischemic stroke. Two hundred forty patients (9% of all consultations; 13.4% of those with acute ischemic stroke) received tPA. Percentages of patients with symptomatic intracranial hemorrhage and 3-month modified Rankin scale scores less than or equal to 1, compared with those in the NINDS trial, were as follows: 3.3% versus 6.4% and 53% versus 43% (P=.04). Mortality rates were 13% (network) versus 17% (NINDS). CONCLUSION: During a 9-year period, an emergency medicine network with stroke consultants achieved patient outcomes comparable to those reported from the NINDS trial. These results indicate that the NINDS tPA protocol is applicable to community practice, with the support of a university-based brain attack center.

Ensuring emergency medicine performance standards for stroke and transient ischemic attack care.

This article reviews emergency medicine evaluation and management performance standards for cerebrovascular event patients and provides a practical process for ensuring high quality care. Areas of practice that most frequently generate questions and controversy are highlighted. The term "cerebrovascular event" is used throughout the text when both stroke and transient ischemic attack apply to the discussion. Recommendations are based on literature review and the author's experience with the successful certification of multiple primary stroke centers and appointments in neurology, emergency medicine, and nursing specialties.

Outcomes from a comprehensive stroke telemedicine program.

Our team has studied the use of telemedicine to overcome obstacles to providing acute stroke care and expanding stroke education. We report a summary of our outcomes to provide evidence supporting greater development of stroke telehealth systems. Stroke telemedicine is audio-video communication (teleconferencing) between a stroke specialist and a remote party requiring stroke services. Using several models, we tested the validity, reliability, and effectiveness of telemedicine versus telephone consultations and face-to-face (traditional) medical care and education. Because of the challenges inherent to technology studies, we found a prospective, case control design most practical for testing hypotheses related to a comparison of telemedicine and traditional service delivery. Telemedicine-assisted neurologic evaluation and stroke diagnosis were as valid and reliable as traditionally delivered services. Clinical effectiveness was demonstrated by shortening times to treatment (17 [telemedicine] vs. 33 [control] minutes; p = 0.003) and increasing tissue plasminogen activator use at a remote hospital (from 5% to 24%). Evaluation of telemedicine as a means to expand stroke education to distant communities revealed that telemedicine and direct education achieve equivalent academic results. Stroke services delivered by telemedicine are safe, efficacious, and comparable to those rendered face-to-face. Telemedicine is a means of providing disability-reducing therapies earlier to a large number of patients. The current, geographically defined scheme for telemedicine service reimbursement fails to recognize that the main barrier to stroke care is lack of available stroke specialists. Contractual and third-party reimbursement structures should be modified to surmount this impediment to extending stroke specialty care and community education.

Evaluation and management of transient ischemic attacks.

The risk for disabling stroke is greatest in the period immediately following a transient ischemic attack (TIA), thus, TIA is a medical emergency. A universities medical center's emergency department-based TIA evaluation and management program is presented as an example of the pragmatic enactment of current guidelines for TIA evaluation and management. A discussion of modifications that can be made for an outpatient setting evaluation and a review of the literature follow.

Anticoagulation strategies for treatment of ischemic stroke and antiphospholipid syndrome: case report and review of the literature.

A 49-year-old Caucasian man with antiphospholipid syndrome who experienced an ischemic stroke required multidisciplinary decisions regarding acute and long-term care. The patient first received warfarin and unfractionated heparin, followed by low-molecular-weight heparin. However, he developed complications from these drugs (warfarin-induced necrosis and heparin-induced thrombocytopenia), resulting in thigh necrosis and multiple additional cerebral and peripheral infarcts. His condition improved after warfarin and the heparins were discontinued, and a direct thrombin inhibitor, argatroban, was given intravenously for acute treatment. Argatroban is the only anticoagulant known to be safe in patients who experience an acute ischemic stroke in the setting of heparin-induced thrombocytopenia. For long-term anticoagulation, fondaparinux, an indirect, selective factor Xa inhibitor, was given subcutaneously. The patient received intravenous dexamethasone, later changed to azathioprine, for immunomodulatory treatment. He had significant improvement in his neurologic deficits without recurrent events over the next 18 months. Management of anticoagulation therapy in patients with antiphospholipid syndrome is complex and challenging, and therapeutic strategies need to be evaluated further.

Alternative parenteral anticoagulation with argatroban, a direct thrombin inhibitor.

Argatroban, a direct thrombin inhibitor, effectively inhibits free and clot-bound thrombin without the need of a cofactor and exerts dose-dependent anticoagulant effects that are rapidly active and rapidly reversible (elimination half-life: 39-51 min). Argatroban provides predictable parenteral anticoagulation and is well tolerated with an acceptably low bleeding risk in a variety of clinical settings, including heparin-induced thrombocytopenia, acute ischemic stroke, percutaneous coronary intervention and hemodialysis. This review will discuss the clinical pharmacology and utility of argatroban; in particular, clinical trial experiences will be discussed in patients with, or at risk of, heparin-induced thrombocytopenia (where heparins must be avoided) including those requiring hemodialysis or percutaneous coronary intervention, and in patients with acute ischemic stroke (where heparins are not generally recommended).

A noninvasive portable acoustic diagnostic system to differentiate ischemic from hemorrhagic stroke.

PURPOSE: To determine if a noninvasive brain acoustic monitor can differentiate acoustic responses from "normal patients" and ischemic from hemorrhagic stroke patients. METHODS: A laptop-sized passive acoustic monitoring system acquires arterial-pressure-generated signals during a 15-second monitoring session from sensors placed at the radial artery and on the fore-head. The arterial pulse waveform from the head is compared with that of the arterial waveform to generate the time-domain signal comparison. Frequency domain signals from each area are also compared. The study involved patients with diagnosis of first stroke who could be monitored within 12 hours of symptom onset and normal subjects who provided informed consent. Individuals with history of brain injury, stroke, or other brain disease were excluded. RESULTS: Twelve normal subjects and 6 ischemic stroke, 2 transient ischemic attack (TIA), and 3 hemorrhagic stroke patients were monitored. Frequency response analysis identified uniform frequency responses in normal subjects. The signal in ischemic stroke patients was characterized by a divergence of the radial and cranial frequency response between 10 and 50 Hz of 10 dB or greater. In intracerebral hemorrhage patients, a divergence was seen below 10 Hz but not in the band above 10 Hz. TIA patients were monitored after symptom resolution and showed a divergence <10 dB in both bands, similar to normal subjects. CONCLUSIONS: In a pilot study using a noninvasive monitor, the authors detected a potential to differentiate between normal subjects and those with cerebral ischemia or hemorrhage.

Acute ischemic stroke successfully treated using sequenced intravenous and intra-arterial thrombolysis and argatroban anticoagulation: a case study.

BACKGROUND: Direct thrombin inhibitors, a class of anticoagulants distinct from heparins, have not been evaluated for immediate use after thrombolytic therapy in acute ischemic stroke. We report a case of ischemic stroke and prothrombotic state treated using sequenced intravenous and intra-arterial thrombolytic therapy and argatroban anticoagulation. CASE DESCRIPTION: A 19-year-old man with a complicated history of recurrent life-threatening thrombosis presented at the emergency department with acute ischemic stroke. The patient received standard-dose intravenous alteplase starting 2.25 hours after symptom onset without change in his global aphasia and right hemiparesis. Five hours after symptom onset, intra-arterial reteplase was administered for treatment of a left internal carotid "T" occlusion, with successful recanalization of the left internal carotid artery, A1 and M1 segments, and right middle cerebral anterior division and with improvement in symptoms. Argatroban therapy was started after completion of intra-arterial thrombolysis, i.e., 8.5 hours after symptom onset, and was maintained for 14 days. Although the patient sustained a small left basal ganglia infarct, he improved significantly over the course of therapy and was discharged to home without bleeding or further thrombotic episodes. CONCLUSIONS: Sequenced intravenous and intra-arterial thrombolytic therapy and argatroban anticoagulation was used successfully to safely treat a patient with ischemic stroke and comorbid prothrombotic state within 8.5 hours of symptom onset.

Argatroban anticoagulation in patients with acute ischemic stroke (ARGIS-1): a randomized, placebo-controlled safety study.

BACKGROUND AND PURPOSE: Direct thrombin inhibitors, including argatroban, represent an anticoagulant class distinct from heparins. We investigated the safety of 2 levels of argatroban anticoagulation in acute ischemic stroke. METHODS: This multicenter, randomized, double-blinded, placebo-controlled study included 171 patients with acute (< or =12 hours from onset) stroke and National Institutes of Health Stroke Scale (NIHSS) scores of 5 to 22. Patients received continuous intravenous argatroban (100 microg/kg bolus) at 3 microg/kg per minute (n=59) or 1 microg/kg per minute (n=58), respectively, adjusted to target activated partial thromboplastin times (aPTTs) 2.25x and 1.75x baseline or placebo (n=54) for 5 days. The primary outcome was symptomatic intracranial hemorrhage (ICH) at 30 days. RESULTS: Baseline characteristics including neurologic deficits (median NIHSS score 9) were comparable between groups. Argatroban at mean doses of 2.7 and 1.2 microg/kg per minute increased aPTTs significantly (P<0.001), with mean aPTTs at or near target values throughout infusion. Symptomatic ICH was not significantly different between groups (high-dose argatroban, 5.1%; low-dose argatroban, 3.4%; placebo, 0%; P> or =0.18), with 3 events during argatroban infusion and 2 events > or =7 days after stopping infusion. No significant between-group differences occurred in asymptomatic ICH (7 events), major systemic hemorrhage (no event), or 90-day mortality (13.4% overall). CONCLUSIONS: In this first North American randomized, double-blinded, placebo-controlled study of direct thrombin inhibition in acute ischemic stroke, argatroban at each dose evaluated significantly prolonged aPTTs without increasing ICH or major bleeding. These results suggest that argatroban provides safe anticoagulation in acute ischemic stroke, warranting future studies powered to evaluate its efficacy and more precisely estimate event rates.

Stroke in patients with heparin-induced thrombocytopenia and the effect of argatroban therapy.

OBJECTIVE: To investigate the frequency, mortality rate, and characteristics of stroke in heparin-induced thrombocytopenia and the effect of argatroban therapy in that setting. DESIGN: Retrospective analysis of two prospective studies of argatroban therapy in heparin-induced thrombocytopenia. SETTING: Hospitalized care. PATIENTS: Patients were 960 patients with heparin-induced thrombocytopenia (767 argatroban-treated patients, 193 historical controls). INTERVENTIONS: Argatroban 2 microg x kg x min, adjusted to achieve activated partial thromboplastin times 1.5-3 times baseline MEASUREMENTS AND MAIN RESULTS: Case records were reviewed to identify patients with stroke present at or within 37 days of study entry and to assess 37-day outcomes. Stroke occurred in 30 (3.1%) patients (stroke at entry, n = 9; new stroke during follow-up, n = 24; more than one stroke, n = 4). By logistic regression with treatment, protocol, age, and gender as covariates, females were significantly more likely to suffer stroke (odds ratio, 2.48; 95% confidence interval, 1.11-5.53; p =.026) and stroke-associated mortality (odds ratio, 4.10; 95% CI, 1.12-15.01; p =.033), and argatroban-treated patients had significantly reduced odds, vs. control, of new stroke (odds ratio, 0.31; 95% confidence interval, 0.10-0.96; p =.041) and stroke-associated mortality (odds ratio, 0.18; 95% confidence interval, 0.03-0.92; p =.039). Stroke (odds ratio, 3.66; 95% confidence interval, 1.73-7.73; p <.001) and age (odds ratio per year, 1.017; 95% confidence interval, 1.004-1.029; p =.008) were significant predictors of all-cause death. In the argatroban group, baseline platelet counts were significantly less in patients with, vs. without, stroke (medians, 42 x 10/L vs. 72 x 10/L; p =.006). Of 35 stroke events, 33 (94%) were ischemic and two (6%) were hemorrhagic (one per group, none during argatroban infusion); 30 (86%) were present at or within 13 days of entry. CONCLUSIONS: Stroke, particularly ischemic stroke, is common in heparin-induced thrombocytopenia and significantly increases mortality risk. Stroke in heparin-induced thrombocytopenia occurs most often in females, in patients with more severe thrombocytopenia, and within 2 wks of heparin-induced thrombocytopenia presentation. Argatroban therapy vs. control significantly reduces the likelihood of new stroke and stroke-associated mortality in heparin-induced thrombocytopenia without increasing intracranial hemorrhage.

Shortening time to stroke treatment using ambulance telemedicine: TeleBAT.

OBJECTIVE: Patients with ischemic stroke treated with tissue plasminogen activator (rt-PA) have better outcomes when treated closer to the time of symptom onset and within the 3-hour window. We previously demonstrated the clinical use of TeleBAT, a mobile telemedicine system for stroke. We tested the impact of that system on time to treatment for patients with acute stroke. METHODS: Validity and reliability were tested by comparing neurologic examination scores obtained using our wireless system, which transmits video of a patient from a moving ambulance to desktop computers, with those obtained using the National Institute of Neurological Disorders and Stroke training videotape. TeleBAT validity and good interrater reliability were defined a priori as a kappa statistic of r > 0.5. We compared the average time to treatment for our TeleBAT-evaluated intervention group with that for our control group. The intervention group consisted of two actor patients with stroke mimicking 12 stroke scenarios and evaluated using TeleBAT. The control group consisted of patients with stroke evaluated and treated with rt-PA on arrival to the emergency department. Data were analyzed using standard t test. RESULTS: National Institutes of Health Stroke Scale items calculated by the neurologists suggest TeleBAT is valid for assessing patients with stroke remotely. Interrater reliability was high: the neurologists gleaned the same information from TeleBAT transmissions. Kappa values for both validity and reliability exceeded 0.5. The mean time to treatment for patients assessed by TeleBAT was 17 +/- 4 minutes compared with 33 +/- 17 minutes for our control group (P = .0033). CONCLUSION: TeleBAT seems to be a valid and reliable means of evaluating stroke neurologic deficits. Time to treatment was shortened using ambulance transport time to evaluate patients as candidates for thrombolytic therapy. Future studies should use a randomized design with patients with acute stroke.

Telemedicine for acute stroke: triumphs and pitfalls.

BACKGROUND AND PURPOSE: Telemedicine is emerging as a potential timesaving, efficient means for evaluating patients experiencing acute stroke. In areas where local stroke care specialists are not available, telemedicine can link an emergency department physician with a specialist in a stroke treatment center. This consultation provides an opportunity for administration of thrombolytic drugs within the short therapeutic time window associated with ischemic stroke. Here, we describe our stroke treatment center experiences and report safe administration of recombinant tissue plasminogen activator (rtPA) during telemedicine consultation. METHODS: The University of Maryland Medical Center uses a triplexed integrated services digital network line providing a 30--frames-per-second video link to St Mary's Hospital >100 miles away. The system uses a pan, tilt, and zoom camera with remote site control, allowing 2-way, real-time, audiovisual communication and CT image transfer. We retrospectively reviewed all acute stroke consultations provided to St Mary's Hospital between 1999 and 2001. RESULTS: We reviewed 50 consultations. Of the 50, 23 were attempted through telemedicine linkage, and 27 were by traditional telephone conversation, followed by transfer. Of the 23 telemedicine consultations, 2 were aborted because of technical difficulties. Of the patients evaluated by traditional means, 1 of 27 (3.8%) received intravenous rtPA; 5 of 21 (23.8%) received rtPA after telemedicine consultation. No patients experienced complications. CONCLUSIONS: Telemedicine consultation provided treatment options not previously available at the remote hospital. Administration of rtPA during telemedicine consultation was feasible and safe, and the system was well received. Lack of reimbursement for telemedicine services will hinder widespread adaptation of this promising technology for remote acute stroke treatment.

Argatroban in thrombotic stroke.

Evidence for the potential use of direct thrombin inhibition in the treatment of acute stroke is reviewed. Reduction of secondary microthrombi and improved regional collateral cerebral blood flow is the proposed mechanism of action of thrombin inhibition for the treatment of cerebral ischemia. A clinical study in Japan found that argatroban administered within 48 h of stroke symptom onset is safe and effective in reducing neurological impairment due to ischemic stroke. The implications of further clinical studies are discussed.