rivaroxaban and Cerebral-Infarction

To assess the incremental benefit of uninterrupted direct oral anticoagulants (DOACs) vs. uninterrupted vitamin K antagonists (VKA) for catheter ablation (CA) of non-valvular atrial fibrillation (NVAF) on three primary outcomes: major bleeding, thrombo-embolic events, and minor bleeding. A secondary outcome was post-procedural silent cerebral infarction (SCI) as detected by brain magnetic resonance imaging.. A systematic review of Medline, Cochrane, and Embase was done to find all randomized controlled trials (RCTs) in which uninterrupted DOACs were compared against uninterrupted VKA for CA of NVAF. A fixed-effect model was used, with the exception of the analysis regarding major bleeding events (I2 > 25), for which a random effects model was used. The benefit of uninterrupted DOACs over VKA was analysed from four RCTs that enrolled a total of 1716 patients (male: 71.2%) with NVAF. Of these, 1100 patients (64.1%) had paroxysmal atrial fibrillation. No significant benefit was seen in major bleeding events [risk ratio (RR) 0.54, 95% confidence interval (95% CI) 0.29-1.00; P = 0.05]. No significant differences were found in minor bleeding events (RR 1.11, 95% CI 0.82-1.52; P = 0.50), thrombo-embolic events (RR 0.74, 95% CI 0.26-2.11; P = 0.57), or post-procedural SCI (RR 1.06, 95% CI 0.74-1.53; P = 0.74).. An uninterrupted DOACs strategy for CA of NVAF appears to be as safe as uninterrupted VKA without a significantly increased risk of minor or major bleeding events. There was a trend favouring DOACs in terms of major bleeding. Given their ease of use, fewer drug interactions and a similar security and effectiveness profile, DOACs should be considered first line therapy in patients undergoing CA for NVAF.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Catheter Ablation; Cerebral Infarction; Dabigatran; Drug Administration Schedule; Factor Xa Inhibitors; Hemorrhage; Humans; Postoperative Complications; Postoperative Hemorrhage; Risk Factors; Rivaroxaban; Severity of Illness Index; Thromboembolism; Warfarin

Japanese Guidelines for the Management of Stroke 2015 was published. Here, we describe several points revised from the 2009 edition about "Cerebral infarction and transient ischemic attack (TIA)". The revision points are as follows; 1. Extension of possible time window of intravenous recombinant tissue-plasminogen activator treatment (from within 3 hours to within 4.5 hours); 2. Antiplatelet therapy in acute stage (dual antiplatelet therapy (DAPT) for non-cardioembolic ischemic stroke or TIA); 3. Endovascular recanalization therapy in acute stage; 4. Antiplatelet therapy in chronic stage (Cilostazol is recommended similar to aspirin or clopidogrel); 5. Non-vitamin K antagonist oral anticoagulants (NOACs) for non-valvular atrial fibrillation (NVAF) stroke or TIA patients; 6. Management of TIA. We explain the revised points of the guideline in the text.

Topics: Acute-Phase Reaction; Anticoagulants; Cerebral Infarction; Dabigatran; Endovascular Procedures; Factor Xa Inhibitors; Humans; Ischemic Attack, Transient; Japan; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Recombinant Proteins; Recurrence; Rivaroxaban; Tissue Plasminogen Activator; Warfarin

Rivaroxaban is an oral highly selective direct factor Xa inhibitor. Rivaroxaban is currently approved for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery, for the treatment of deep vein thrombosis and pulmonary embolism and long-term secondary prevention of venous thromboembolism, and for stroke and systemic embolism prevention in patients with nonvalvular atrial fibrillation. Rivaroxaban has many advantages over vitamin K antagonists and this may facilitate its use in clinical practice. As a result, it is expected that new oral anticoagulants may change patient management strategies. On the other hand, rivaroxaban has some particularities that are necessary to know. The aim of this manuscript was to review the use of rivaroxaban not only in general population, but also in specific patients groups and clinical situations to achieve an optimal management with this drug in daily clinical practice.. Aspectos practicos de la administracion de rivaroxaban.. El rivaroxaban es un inhibidor oral altamente selectivo del factor Xa. Actualmente, el uso de rivaroxaban esta aprobado para la prevencion del tromboembolismo venoso en adultos a los que se va a realizar un reemplazo electivo tanto de rodilla como de cadera, para el tratamiento de la trombosis venosa profunda y embolia de pulmon y la prevencion secundaria a largo plazo del tromboembolismo venoso, y para la prevencion del ictus y del embolismo sistemico en pacientes con fibrilacion auricular no valvular. El rivaroxaban posee multiples ventajas sobre los antagonistas de la vitamina K, y esto puede facilitar su uso en la practica clinica. En consecuencia, es probable que los nuevos anticoagulantes cambien las estrategias de manejo de los pacientes que requieran anticoagulacion. Por otra parte, el rivaroxaban tiene algunas particularidades que es necesario conocer. El objetivo de este articulo ha sido revisar el uso del rivaroxaban no solo en la poblacion general, sino tambien en diferentes subgrupos de pacientes y situaciones clinicas, para asi lograr un manejo optimo de este farmaco en la practica clinica diaria.

Topics: Anticoagulants; Cerebral Infarction; Humans; Morpholines; Risk Factors; Rivaroxaban; Surgical Procedures, Operative; Thiophenes

Novel oral anticoagulants (NOAC) such as the direct thrombin inhibitor, dabigatran, and oral factor Xa inhibitors, rivaroxaban and apixaban, have recently approved for prevention of stroke in nonvalvular atrial fibrillation (NVAF). Phase III trials have compared each of these agents to warfarin. Dabigatran was more efficacious than warfarin in reducing the risk of stroke when given at a dose of 150 mg BID to patients with NVAF. Rivaroxaban 20 mg QD was superior to warfarin in on-treatment analysis. Apixaban 5 mg BID was also found to be superior to warfarin in reducing stroke in NVAF patients. Of note, the rate of hemorrhagic stroke was much smaller in the patients treated with NOAC than those with warfarin. NOAC offer a good therapeutic option for prevention of stroke in NVAF patients.

Topics: Administration, Ophthalmic; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cerebral Infarction; Clinical Trials, Phase III as Topic; Dabigatran; Factor Xa Inhibitors; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Warfarin

Treatment with vitamin K antagonists are subject to a common iatrogenic mainly characterized by hemorrhagic stroke. Their narrow therapeutic range associated with variability largely explains this phenomenon. New oral anticoagulants (NOAC) are now available. dabigatran (Pradaxa®) is a direct and specific thrombin inhibitor. It is excreted mainly by the kidney and is the only which can be dialyzed. Rivaroxaban (Xarelto®) and apixaban (Eliquis®) are factor X activated direct inhibitors. They are highly bound to plasma proteins and are metabolized mainly by the liver, via CYP3A4. All NOAC are substrates of P-glycoprotein (P-gp). Due to pharmacological changes, some populations at risk were identified: patients with hepatic impairment, renal impairment, elderly patients or low weight. Some pharmacokinetic or pharmacodynamic drug interactions alter the concentration and the expected impact of NOAC. The NOAC does not require biological monitoring. They interfere with the routine coagulation tests which should be interpreted with caution. Specific tests exist and can be used in case of emergencies. Currently, no antidote is available. The new oral anticoagulant look promising in the elderly. However, certain rules must be followed to reduce the risk of iatrogenic.

Topics: Administration, Oral; Aged; Anticoagulants; Benzimidazoles; beta-Alanine; Cerebral Infarction; Dabigatran; Dose-Response Relationship, Drug; Drug Interactions; Drugs, Investigational; Humans; Iatrogenic Disease; Intracranial Hemorrhages; Morpholines; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Vitamin K

This randomized study compared uninterrupted rivaroxaban therapy with warfarin therapy as prophylaxis against catheter ablation (CA)-induced asymptomatic cerebral infarction (ACI) and identified the risk factors of rivaroxaban.. The reported incidence of ACI during CA for atrial fibrillation (AF) remains at 10% to 30%, and periprocedural oral anticoagulation could affect this incidence.. Patients with nonvalvular AF undergoing radiofrequency CA were randomly assigned to receive either uninterrupted rivaroxaban or warfarin as periprocedural anticoagulation therapy. CA was performed after at least 1 month of adequate anticoagulation. Cerebral magnetic resonance imaging (MRI) was performed within 2 weeks before and 1 day after CA to detect ACI.. A total 132 patients were enrolled; 127 (median: 60.0 years of age; 83.5% males; 64.6% incidence of paroxysmal AF) complied with the study protocol and were analyzed; 64 patients received rivaroxaban, and 63 patients received warfarin. The rates of CA-induced ACI in the rivaroxaban group (15.6% [10 of 64 patients]) were similar to those in the warfarin group (15.9% [10 of 63 patients]; p = 1.000). No thromboembolic events developed; no differences in major or nonmajor bleeding rates were observed between the 2 drug groups (3.1% vs. 1.6%, respectively, or 18.8% vs. 19.0%, respectively). Multiple regression analysis indicated that the presence of deep and subcortical white matter hyperintensity (p = 0.002; odds ratio [OR]: 5.323) and the frequency of cardioversions (p = 0.016; OR: 1.250) were associated with the incidence of ACI.. No notable differences were found between the incidence of CA-induced ACI in the rivaroxaban group and that in the warfarin group in this randomized study.

Topics: Aged; Anticoagulants; Asymptomatic Diseases; Atrial Fibrillation; Brain; Catheter Ablation; Cerebral Infarction; Female; Humans; Incidence; Intraoperative Complications; Male; Middle Aged; Risk Factors; Rivaroxaban; Warfarin

It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect.. Ten-week-old C57Bl/6 mice (n = 338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1 to 4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1 to 3 days received single-dose aspirin. Thereafter, we induced FeCl. We observed a ~ 40% higher volume of carotid thrombus after dabigatran cessation at 1 to 3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through thrombin or arachidonic acid, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤ 3 days) cessation of NOAC therapy, compared with longer-term (≥ 5 days) cessation, tended to be associated with relatively high stroke severity.. We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. ANN NEUROL 2021;89:444-458.

Topics: Aged; Aged, 80 and over; Animals; Antithrombins; Arachidonic Acid; Aspirin; Carotid Artery Thrombosis; Cerebral Infarction; Chlorides; Computed Tomography Angiography; Dabigatran; Deprescriptions; Factor Xa Inhibitors; Female; Ferric Compounds; Humans; Ischemic Stroke; Magnetic Resonance Angiography; Male; Mean Platelet Volume; Mice; Noxae; Pilot Projects; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Pyrazoles; Pyridones; Rivaroxaban; Severity of Illness Index; Substance Withdrawal Syndrome; Thrombin; Thrombophilia; X-Ray Microtomography

There is little data on management and outcomes of atrial fibrillation (AF) patients on direct oral anticoagulants (DOAC) undergoing general surgery.We retrospectively assessed 98 surgeries in 85 nonvalvular AF patients aged 73 ± 8 (59 men) receiving DOACs. Cardiac, emergency, and minimally invasive surgeries were excluded.The CHA

Topics: Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Blood Loss, Surgical; Carotid Artery Diseases; Cerebral Infarction; Dabigatran; Digestive System Surgical Procedures; Elective Surgical Procedures; Embolism; Endoscopy; Factor Xa Inhibitors; Female; Humans; Male; Myocardial Infarction; Orthopedic Procedures; Perioperative Care; Postoperative Complications; Postoperative Hemorrhage; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Thiazoles; Thromboembolism; Urologic Surgical Procedures; Vascular Surgical Procedures

Benign gynecologic tumor, such as uterine adenomyosis, has been suggested to develop hypercoagulability. Although some cases of cerebral infarction associated with adenomyosis have been reported, the mechanism of hypercoagulation initiated by adenomyosis is still not clear, and the therapeutic strategy is uncertain.. A 44-year-old woman was presented to our department with headache, left hand weakness, and gait disturbance during her menstrual phase. She had a history of adenomyosis and infertility treatment for 18 years and heavy menstrual bleeding. Magnetic resonance imaging on admission showed multiple hyperintense lesions in cortical and subcortical areas in the cerebrum and cerebellum on diffusion-weighted imaging. Transesophageal echocardiography showed neither embolic sources nor existence of foramen ovale. Her laboratory data revealed anemia, a high D-dimer level, and elevated levels of a mucinous tumor marker. She had adenomyosis and no malignancy was detected. Anticoagulation therapy with intravenous heparin followed by rivaroxaban did not prevent recurrence of cerebral infarction. We discontinued rivaroxaban, and started warfarin therapy with pseudomenopause treatment, which prevented recurrence for 6 months. Five months after her last pseudomenopause treatment, multiple cerebral infarctions occurred. Total hysterectomy was performed, which prevented recurrence of the multiple cerebral infarctions for 2 years without anticoagulation therapy.. Our findings reveal for the first time that anticoagulation therapy, including novel oral anticoagulants, had no preventive effect against cerebral infarctions associated with adenomyosis in a middle-aged woman. Although pseudomenopause treatment temporarily prevented recurrence, resection of the adenomyosis might be the most effective therapy in these cases.

Topics: Adenomyosis; Adult; Anticoagulants; Cerebral Infarction; Female; Humans; Hysterectomy; Rivaroxaban

Topics: Antiphospholipid Syndrome; Cerebral Infarction; Diagnosis, Differential; Edema; Electrocardiography; Factor Xa Inhibitors; Female; Humans; Leg; Middle Aged; Rivaroxaban

Topics: Atrial Fibrillation; Catheter Ablation; Cerebral Infarction; Humans; Rivaroxaban; Warfarin

Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Benzimidazoles; beta-Alanine; Cerebral Infarction; Dabigatran; Drug Substitution; Female; Humans; International Normalized Ratio; Lupus Erythematosus, Systemic; Male; Mesenteric Veins; Middle Aged; Morpholines; Portal Vein; Recurrence; Retrospective Studies; Rivaroxaban; Splenic Vein; Stroke; Thiophenes; Thromboembolism; Thrombophilia; Treatment Failure; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Cerebral Infarction; Double-Blind Method; Humans; International Normalized Ratio; Morpholines; Multicenter Studies as Topic; Phenprocoumon; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Stroke; Thiophenes