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The Lancet. Neurology May 2021Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with cervical artery dissection, although some current guidelines-based on available evidence from mostly observational studies-suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection.
METHODS
We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio [INR] 2·0-3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460.
FINDINGS
Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% [95% CI -4 to 21], non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group.
INTERPRETATION
Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection.
FUNDING
Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.
Topics: Acenocoumarol; Adult; Anticoagulants; Aspirin; Carotid Artery, Internal, Dissection; Denmark; Female; Germany; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Stroke; Switzerland; Vertebral Artery Dissection; Warfarin
PubMed: 33765420
DOI: 10.1016/S1474-4422(21)00044-2 -
The New England Journal of Medicine Dec 2010Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring.
METHODS
We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study.
RESULTS
The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin-vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11).
CONCLUSIONS
Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; ClinicalTrials.gov numbers, NCT00440193 and NCT00439725.).
Topics: Acenocoumarol; Acute Disease; Administration, Oral; Aged; Anticoagulants; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Injections, Subcutaneous; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin
PubMed: 21128814
DOI: 10.1056/NEJMoa1007903 -
Journal of Thrombosis and Haemostasis :... Jun 2015The utility of using genetic information to guide warfarin dosing has remained unclear based on prior observational studies and small clinical trials. Two larger trials... (Review)
Review
The utility of using genetic information to guide warfarin dosing has remained unclear based on prior observational studies and small clinical trials. Two larger trials of warfarin and one of the acenocoumarol and phenprocoumon have recently been published. The COAG trial addressed the incremental benefit of adding genetic information to clinical information and demonstrated no benefit from the pharmacogenetic-based dosing strategy on the primary outcome. The EU-PACT UK trial compared an algorithm approach using genetic and clinical information to one that used a relatively fixed starting dose. The pharmacogenetic-based algorithms improved the primary outcome. The study of acenocoumarol and phenprocoumon compared a pharmacogenetic with a clinical algorithm and demonstrated no benefit on the primary outcome. The evidence to date does not support an incremental benefit of adding genetic information to clinical information on anticoagulation control. However, compared with fixed dosing, a pharmacogenetic algorithm can improve anticoagulation control.
Topics: Algorithms; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Drug Dosage Calculations; Drug Monitoring; Genotype; Humans; Pharmacogenetics; Phenotype; Precision Medicine; Predictive Value of Tests; Treatment Outcome; Warfarin
PubMed: 26149035
DOI: 10.1111/jth.12978 -
The New England Journal of Medicine Jul 2003Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer.
METHODS
Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months).
RESULTS
During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group.
CONCLUSIONS
In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.
Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Dalteparin; Drug Therapy, Combination; Female; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Secondary Prevention; Survival Analysis; Thromboembolism; Venous Thrombosis; Warfarin
PubMed: 12853587
DOI: 10.1056/NEJMoa025313 -
Journal of Clinical and Experimental... Feb 2017Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. A new group of oral anticoagulants with clear advantages over classic... (Review)
Review
BACKGROUND
Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. A new group of oral anticoagulants with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. The Food and Drug Administration has approved edoxaban, dabigatran, rivaroxaban and apixaban. Their advantages include: predictable pharmacokinetics, drug interactions and limited food, rapid onset of action and short half-life. However, they lack a specific reversal agent.
MATERIAL AND METHODS
This paper examines the available evidence regarding rivaroxaban and sets out proposals for clinical guidance of dental practitioners treating these patients in primary dental care. A literature search was conducted through July 2016 for publications in PubMed and Cochrane Library using the keywords "edoxaban", "dabigatran", "rivaroxaban", "apixaban", "new oral anticoagulants", "novel oral anticoagulants", "bleeding" and "dental treatment" with the "and" boolean operator in the last 10 years.
RESULTS
The number of patients taking edoxaban is increasing. There is no need for regular coagulation monitoring of patients on edoxaban therapy. For patients requiring minor oral surgery procedures, interruption of edoxaban is not generally necessary. Management of patients on anticoagulation therapy requires that dentists can accurately assess the patient prior to dental treatments.
CONCLUSIONS
Their increased use means that oral care clinicians should have a sound understanding of the mechanism of action, pharmacology, reversal strategies and management of bleeding in patients taking edoxaban. There is a need for further clinical studies in order to establish more evidence-based guidelines for dental patients requiring edoxaban. Edoxaban, dabigatran, rivaroxaban, apixaban, novel oral anticoagulants, bleeding.
PubMed: 28210454
DOI: 10.4317/jced.53431 -
Journal of Clinical and Experimental... Dec 2016Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. Recently, new oral anticoagulants have been introduced as alternatives to... (Review)
Review
BACKGROUND
Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. Recently, new oral anticoagulants have been introduced as alternatives to warfarin and acenocoumarol. In Europe, the European Medicines Agency has approved dabigatran, rivaroxaban and apixaban. Their advantages include: predictable pharmacokinetics, drug interactions and limited food, rapid onset of action and short half-life. However, they lack a specific reversal agent.
MATERIAL AND METHODS
A literature search was conducted through November 2015 for publications in the ISI Web of Knowledge, PubMed, Scopus and Cochrane Library using the keywords "apixaban", "rivaroxaban", "dabigatran", "new oral anticoagulants", "dental treatment" and "dental implications". We included studies published in English and Spanish over the last 10 years.
RESULTS
Apixaban has been recently introduced in the daily medical practices for the control of thromboembolism. The number of patients taking apixaban is increasing. Management of patients on anticoagulation therapy requires that dentists can accurately assess the patient prior to dental treatments. It is important for dentists to have a sound understanding of the mechanisms of action and management guidelines for patients taking new oral anticoagulants.
CONCLUSIONS
The dentist should consider carefully the management of patients on apixaban. This paper sets out a clinical guidance of dental practitioners treating these patients. There is a need for further clinical studies in order to establish more evidence-based guidelines for dental patients requiring apixaban. Apixaban, new oral anticoagulants, dental treatment.
PubMed: 27957279
DOI: 10.4317/jced.53004 -
Journal of Clinical and Experimental... Oct 2015Thrombotic disorders remain a leading cause of death in the Western world, and in this regard a number of anticoagulation treatment have been used, including heparins,... (Review)
Review
BACKGROUND
Thrombotic disorders remain a leading cause of death in the Western world, and in this regard a number of anticoagulation treatment have been used, including heparins, fondaparinux, vitamin K antagonists (warfarin, acenocoumarol), and new oral anticoagulants such as apixaban. For years there has been great controversy regarding the use of anticoagulants in planning dental treatments that imply bleeding. The main concerns about using new oral anticoagulants in invasive dental procedures are bleeding due to the lack of an antidote, and the thrombotic risk of the disease for which anticoagulation was indicated in the first place.
MATERIAL AND METHODS
A literature search was conducted through May 2014 using the keyword "apixaban" for publications in the ISI Web of Knowledge. The search was extended to other databases (PubMed, Scopus and the Cochrane Library).
RESULTS
Based on the results of the different studies, apixaban seems to be a good alternative to conventional anticoagulation and a reasonable treatment option, though its main and most common adverse effect is bleeding. Dose adjustment is needed in some patients, though regular laboratory monitoring is not required. The use of the drug in different patient populations will define its final indications and doses.
CONCLUSIONS
Regarding the use of apixaban in the dental setting, there is a compelling need for further clinical studies in order to establish more evidence-based guidelines for patients requiring antithrombotic treatment.
KEY WORDS
Apixaban, dental treatment, dental implications.
PubMed: 26535102
DOI: 10.4317/jced.52470 -
Revista Espanola de Enfermedades... May 2018We report the case of a 65-year-old male patient with Down's syndrome and a deep venous thrombosis on anticoagulation with acenocoumarol. The case presented due to...
We report the case of a 65-year-old male patient with Down's syndrome and a deep venous thrombosis on anticoagulation with acenocoumarol. The case presented due to nonspecific, predominantly postprandial epigastric discomfort, meteorism and aerophagia. A thoracoabdominal computed tomography (CT) scan revealed a Morgagni hernia with a cephalad migration of part of the stomach, ascending colon and transverse colon. After laparotomy, the defect was repaired using a titanium mesh and the patient had a favorable outcome.
Topics: Age of Onset; Aged; Hernias, Diaphragmatic, Congenital; Humans; Male
PubMed: 29745721
DOI: 10.17235/reed.2018.5425/2017 -
Journal of Clinical and Experimental... Feb 2017A new group of oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban) with clear advantages over classic dicoumarin oral anticoagulants (warfarin and... (Review)
Review
BACKGROUND
A new group of oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban) with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. Patients being treated with oral anticoagulants are at higher risk for bleeding when undergoing dental treatments.
MATERIAL AND METHODS
A literature search was conducted through April 2016 for publications in the ISI Web of Knowledge, PubMed and Cochrane Library using the keywords "dabigatran", "rivaroxaban", "apixaban", "edoxaban", "new oral anticoagulants", "novel oral anticoagulants", "bleeding" and "dental treatment".
RESULTS
There is no need for regular coagulation monitoring of patients on dabigatran therapy. Whether or not to temporarily discontinue dabigatran must be assessed according to the bleeding risk involved in the dental procedure to be performed.
CONCLUSIONS
The number of patients under treatment with new oral anticoagulants will increase in the coming years. It is essential to know about the pharmacokinetics and pharmacodynamics of new oral anticoagulants and about their interactions with other drugs. It is necessary to develop clinical guidelines for the perioperative and postoperative management of these new oral anticoagulants in oral surgical procedures, and to carefully evaluate the bleeding risk of dental treatment, as well as the thrombotic risk of suppressing the new oral anticoagulant. Dabigatran, rivaroxaban, apixaban, edoxaban, novel oral anticoagulants, bleeding.
PubMed: 28210451
DOI: 10.4317/jced.53219