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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 -
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 -
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 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 -
Pharmaceuticals (Basel, Switzerland) Apr 2023Hyperpigmentation can occur in abnormal skin conditions such as melanomas, as well as in conditions including melasma, freckles, age spots, seborrheic keratosis, and...
Hyperpigmentation can occur in abnormal skin conditions such as melanomas, as well as in conditions including melasma, freckles, age spots, seborrheic keratosis, and café-au-lait spots (flat brown spots). Thus, there is an increasing need for the development of depigmenting agents. We aimed to repurpose an anticoagulant drug as an effective ingredient against hyperpigmentation and apply cosmeceutical agents. In the present study, the anti-melanogenic effects of two anticoagulant drugs, acenocoumarol and warfarin, were investigated. The results showed that both acenocoumarol and warfarin did not cause any cytotoxicity and resulted in a significant reduction in intracellular tyrosinase activity and melanin content in B16F10 melanoma cells. Additionally, acenocoumarol inhibits the expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2, suppressing melanin synthesis through a cAMP-dependent, protein kinase (PKA)-dependent downregulation of microphthalmia-associated transcription factor (MITF), a master transcription factor in melanogenesis. Furthermore, anti-melanogenic effects were exerted by acenocoumarol through downregulation of the p38 and JNK signaling pathway and upregulation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthesis kinase-3β (GSK-3β) cascades. In addition, the β-catenin content in the cell cytoplasm and nucleus was increased by acenocoumarol through a reduction in the phosphorylated β-catenin (p-β-catenin content). Finally, we tested the potential of acenocoumarol for topical applications by conducting primary human skin irritation tests. Acenocoumarol did not induce any adverse reactions during these tests. Based on the results, it can be concluded that acenocoumarol regulates melanogenesis through various signaling pathways such as PKA, MAPKs, PI3K/Akt/GSK-3β, and β-catenin. These findings suggest that acenocoumarol has the potential to be repurposed as a drug for treating hyperpigmentation symptoms and could provide new insights into the development of therapeutic approaches for hyperpigmentation disorders.
PubMed: 37111361
DOI: 10.3390/ph16040604 -
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 -
Prilozi (Makedonska Akademija Na... Jul 2022Genetic factors play an important role in deep vein thrombosis (DVT). The duration of anticoagulation therapy in patients with verified genetic inheritance and previous...
Genetic factors play an important role in deep vein thrombosis (DVT). The duration of anticoagulation therapy in patients with verified genetic inheritance and previous events of DVT is still questionable. We present three cases of siblings (two brothers and one sister) with verified Venous thromboembolism (VTE) and genetic inheritance. The first case is a 33 y.o. male who was admitted with bilateral massive pulmonary thromboembolism and DVT of the right femoral vein. He had an episode of DVT 4 years ago. Fibrinolytic therapy was introduced immediately. Afterwards, unfractionated heparin was introduced, and then switched to enoxaparin and acenocoumarol. Because of inappropriate INR, it was switched then to rivaroxaban. The imaging methods showed significant improvement, and the patient was discharged from the hospital with rivaroxaban at 2x15 mg/day for another 2 weeks and was instructed to continue 20 mg/day until his next control. In the meantime, the second case, a 36 y.o. male, brother to the first patient, came with vein thrombosis of vena saphena magna of the left leg. Treatment with Acenocoumarol was started and continued for 2 years until complete resolution of the thrombi, and then it was changed to Aspirin. The third case is the sister of the first 2 cases, a 38 y.o female with symptoms and findings almost similar to those in the second case. She was treated with Acenocoumarol for 6 months. Doppler ultrasound showed complete resolution of the thrombosis and anticoagulation therapy was stopped. Genetic investigations for mutation showed presence of homozygous gene mutation for () in the first patient, his brother (the second case) was compound heterozygote for PTB and for , and his sister (third case) was heterozygous only for the mutation. According to the clinical (recurrent unprovoked DVT with thromboembolic complications) and genetic testing (homozygous gene mutation for ) in the first patient, we decided to continue the secondary thromboprophylaxis with rivaroxaban 10 mg/day indefinitely. Testing for genetically inherited thrombophilia should be included in the risk assessment for recurrence, and performed in all patients under 50 y.o. who have a first, non-provoked episode of thrombosis, in order to determine the duration of anticoagulation therapy.
Topics: Acenocoumarol; Anticoagulants; Female; Heparin; Humans; Male; Rivaroxaban; Thrombophilia; Thrombosis; Venous Thromboembolism; Venous Thrombosis
PubMed: 35843922
DOI: 10.2478/prilozi-2022-0016