The Argatroban and Tissue-Type Plasminogen Activator Stroke Study

Barreto, Andrew D; Alexandrov, Andrei V.; Lyden, Pat; Lee, Jessica; Martin‐Schild, Sheryl; Shen, Lan; Wu, Tzu Ching; Sisson, April; Pandurengan, Renganayaki; Chen, Zhongxue; Rahbar, Mohammad Hossein; Balucani, Clotilde; Barlinn, Kristian; Sugg, Rebecca; Garami, Zsolt; Tsivgoulis, Georgios; Gonzales, Nicole R.; Savitz, Sean I; Mikulík, Robert; Demchuk, Andrew M.; Grotta, James C.

doi:10.1161/strokeaha.111.625574

Cited by 95 publications

(89 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In more recent case reports, tissue plasminogen activator (tPA), a potent fibrinolytic agent, has shown promise in ameliorating cast burden in plastic bronchitis of non-SM causes (7-10), but only anecdotally. tPA is currently used as firstline therapy in several clot-associated diseases, such as stroke (35,36) and myocardial infarction (37), and can improve survival with these life-threatening entities. In regard to plastic bronchitis, no placebo-controlled clinical trials have been done to evaluate the effects of tPA.…”

Section: Clinical Relevancementioning

confidence: 99%

Tissue Plasminogen Activator Prevents Mortality from Sulfur Mustard Analog–Induced Airway Obstruction

Veress

Hendry‐Hofer²,

Loader³

et al. 2013

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Sulfur mustard (SM) inhalation causes the rare but life-threatening disorder of plastic bronchitis, characterized by bronchial cast formation, resulting in severe airway obstruction that can lead to respiratory failure and death. Mortality in those requiring intubation is greater than 80%. To date, no antidote exists for SM toxicity. In addition, therapies for plastic bronchitis are solely anecdotal, due to lack of systematic research available to assess drug efficacy in improving mortality and/or morbidity. Adult rats exposed to SM analog were treated with intratracheal tissue plasminogen activator (tPA) (0.15-0.7 mg/kg, 5.5 and 6.5 h), compared with controls (no treatment, isoflurane, and placebo). Respiratory distress and pulse oximetry were assessed (for 12 or 48 h), and arterial blood gases were obtained at study termination (12 h). Microdissection of fixed lungs was done to assess airway obstruction by casts. Optimal intratracheal tPA treatment (0.7 mg/kg) completely eliminated mortality (0% at 48 h), and greatly improved morbidity in this nearly uniformly fatal disease model (90-100% mortality at 48 h). tPA normalized plastic bronchitis-associated hypoxemia, hypercarbia, and lactic acidosis, and improved respiratory distress (i.e., clinical scores) while decreasing airway fibrin casts. Intratracheal tPA diminished airwayobstructive fibrin-containing casts while improving clinical respiratory distress, pulmonary gas exchange, tissue oxygenation, and oxygen utilization in our model of severe chemically induced plastic bronchitis. Most importantly, mortality, which was associated with hypoxemia and clinical respiratory distress, was eliminated.Keywords: plastic bronchitis; tissue plasminogen activator; airway obstruction; sulfur mustard; fibrin Sulfur mustard (bis(2-chloroethyl)sulfide; SM) is a vesicant and chemical weapon used in warfare during much of the twentieth century, and which remains in the stockpiles of multiple nations today (Syria, Iran, North Korea, Libya, the United States, and possibly others). SM exposure affects the eyes, skin, upper airways, and lungs. After a brief latent period, respiratory failure and death can develop within 12 to 48 hours. Despite a century of study, the mechanisms responsible for SM's toxic effects remain unsolved, and clinically effective rescue therapies or antidotes are not available.Initial reports of human SM inhalation toxicity in the early 1900s described the presence of airway-obstructive necrotic debris/ mucosa, or "pseudomembranes," in the large airways of victims, and these were more recently confirmed in the victims of the IranIraq war (1, 2). Such severe lesions have been reported to lead to respiratory compromise, with need for artificial ventilation, and death in 80% of those needing intubation (2). Furthermore, chronic conducting airway lesions, such as bronchiolitis obliterans, tracheal/bronchial stenosis, and chronic bronchitis, are commonly found in survivors of SM inhalation months to years after exposure (2, 3), whereas chronic alveolar or paren...

show abstract

Section: Clinical Relevancementioning

confidence: 99%

Tissue Plasminogen Activator Prevents Mortality from Sulfur Mustard Analog–Induced Airway Obstruction

Veress

Hendry‐Hofer²,

Loader³

et al. 2013

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…On the contrary, the Argatroban tPA Stroke Study (ARTSS-1) evaluated the safety of argatroban use in combination with r-tPA in patients with ischemic stroke. 13 The effectiveness or safety of the combination therapy could not be evaluated in the present study. A recently conducted randomized controlled trial on combination therapy (ARTSS-2) should provide further information on the efficacy and safety of combination therapy.…”

mentioning

confidence: 91%

Outcomes of Argatroban Treatment in Patients With Atherothrombotic Stroke

Wada

Yasunaga

Horiguchi

et al. 2016

Stroke

View full text Add to dashboard Cite

Background and Purpose-Argatroban, a selective thrombin inhibitor, is recommended for the use in patients with atherothrombotic stroke by the Japanese Guidelines for the Management of Patients with Acute Ischemic Stroke. We performed a nationwide Japanese study to investigate whether argatroban improved early stroke outcomes in patients with acute atherothrombotic stroke. Methods-This retrospective observational study, using the Diagnosis Procedure Combination database in Japan, included patients who were hospitalized from July 1, 2010, to March 31, 2012, with a diagnosis of atherothrombotic stroke within 1 day of stroke onset. Patients were divided into 2 groups: those receiving argatroban on admission (argatroban group), and those who did not receive argatroban during hospitalization (control group). To balance the baseline characteristics and concomitant treatments during hospitalization between the 2 groups, one-to-one propensity-score matching analyses were performed. The main outcomes were the modified Rankin Scale score at discharge and the occurrence of hemorrhagic complications during hospitalization. An ordinal logistic regression analysis evaluated the association between argatroban use and modified Rankin Scale at discharge. Results-After propensity-score matching, 2289 pairs of patients were analyzed. There were no significant differences in modified Rankin Scale at discharge between the argatroban and the control groups (adjusted odds ratio, 1.01; 95% confidence interval, 0.88-1.16). The occurrence of hemorrhagic complications did not differ significantly between the argatroban and the control groups (3.5% versus 3.8%; P=0.58). Conclusions-The present study suggested that argatroban was safe, but had no added benefit in early outcomes after acute atherothrombotic stroke. The aim of the present study was to investigate whether argatroban was effective and safe in patients with acute ischemic stroke, using a database of Japanese inpatients. Methods Study Design and SettingThis was a retrospective observational cohort study using data from a nationwide administrative claims and discharge abstract database in Japan, the Diagnosis Procedure Combination database. The Diagnosis Procedure Combination database has been described in detail previously. 9 In brief, >1000 hospitals, including all 82 academic hospitals in Japan, contribute to the Diagnosis Procedure Combination database. The annual number of cases added to the database is ≈7 000 000 and encompasses ≈50% of all hospital admissions in Japan.The Diagnosis Procedure Combination database contains the following information for each patient: patient demographics, a unique hospital identifier, diagnoses, outcomes, drugs used, procedures performed, healthcare costs, and several disease-specific data. Diagnoses include the main diagnosis on admission, preexisting comorbidities, and postadmission complications, which are recorded separately with International Classification of Diseases-10th revision codes and text data in Japanese. Drugs and procedures ar...

show abstract

“…In practice, argatroban was started at a median of 51 minutes after tPA, and the target anticoagulation was reached at a median of 3 hours. 1 Although recanalization (assessed using transcranial Doppler or CT angiography) occurred in 61% of patients (29 of 47) at 2 hours, significant intracerebral hemorrhage (the primary outcome) occurred in 6% (4 patients, and symptomatic intracranial hemorrhage in 4.6%, 3 patients). Seven (10%) patients died over the first 7 days.…”

mentioning

confidence: 98%

“…Although the first is proven, the second and third remain without definitive data, although clinical research continues, as highlighted in the linked article by Baretto and colleagues who describe results from a small Phase II study of argatroban, an intravenous anticoagulant. 1 After numerous neutral trials of unfractionated heparin, 2 low-molecular-weight heparin, 3,4 and low-molecular-weight heparinoids, 5 it might seem strange to be testing another anticoagulant in the management of acute ischemic stroke. Meta-analyses of completed trials showed that anticoagulation did not alter functional outcome and that any apparent benefit in reducing early recurrence was offset by an increase in symptomatic intracranial hemorrhage.…”

mentioning

confidence: 99%

“…1 Argatroban was administered open label without a comparator group as a bolus (100 g/kg bolus given over 3-5 minutes) within 1 hour of tissue-type plasminogen activator (tPA) and then dose-adjusted from 1.0 g/kg per minute to maintain the activated partial thromboplastin time at 1.75 times baseline over 48 hours. In practice, argatroban was started at a median of 51 minutes after tPA, and the target anticoagulation was reached at a median of 3 hours.…”

mentioning

confidence: 99%

See 1 more Smart Citation