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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 -
Medicina Clinica Jul 2023The objective of the systematic review is to analyze the efficacy of direct-acting oral anticoagulants (DOAC) in the prophylaxis of thrombosis in antiphospholipid... (Review)
Review
The objective of the systematic review is to analyze the efficacy of direct-acting oral anticoagulants (DOAC) in the prophylaxis of thrombosis in antiphospholipid syndrome (APS). We searched for clinical trials, cohort studies and meta-analyses published from January 1, 2012 to September 30, 2022. Articles that analyzed the efficacy of DOAC in the prevention of thrombosis recurrence, with or without comparison with antivitamin K (VKA) drugs, were selected. DOACs, specifically rivaroxaban and apixaban, were significantly less effective than VKAs in preventing recurrence of thrombosis in patients with APS and prior arterial thrombosis or the concomitant presence of two or three different antiphospholipid antibodies. The proportion of patients with severe bleeding as side effect are similar in those treated with DOAC and with VKA. The results argue against the use of DOAC in the treatment of patients with thrombotic APS.
Topics: Humans; Antiphospholipid Syndrome; Anticoagulants; Factor Xa Inhibitors; Warfarin; Thrombosis; Administration, Oral
PubMed: 37105842
DOI: 10.1016/j.medcli.2023.03.011 -
FEMS Microbiology Letters Oct 2021The increased interest of consumers in probiotic foods requires a deeper knowledge on the possible interactions with drugs, because their pharmacological properties...
The increased interest of consumers in probiotic foods requires a deeper knowledge on the possible interactions with drugs, because their pharmacological properties could be modified. In this context, these studies are relevant for drugs such as acenocoumarol, whose dosage must be controlled due to, among other factors, food-drug interactions. Acenocoumarol is an oral anticoagulant with a narrow therapeutic range. The aim of the present research is to evaluate, in vitro, the effect of bifidobacteria on acenocoumarol. The drug was incubated with Bifidobacterium bifidum CIDCA 5310 or Bifidobacterium adolescentis CIDCA 5317 in MRS broth at 37°C for 24 h in anaerobic conditions. The effect of incubation with sterilized spent culture supernatants (SSCS) was also evaluated. Analysis by RP-HPLC showed that both bifidobacterial strains reduced the area of the acenocoumarol peak and two new peaks were evidenced. In addition, a decrease in the intensity of the bands at 1650, 1390 and 1110/cm was observed in the FTIR spectroscopic determinations. Moreover, a new band appeared at 1720/cm. No effect on the drug was observed when incubation was performed with SSCS. The present study showed a significant change in the concentration of the anticoagulant after incubation with bifidobacteria and results are compatible with biomodification of the drug due to enzymatic activity of bifidobacteria.
Topics: Acenocoumarol; Anticoagulants; Bifidobacterium; Drug Interactions; Probiotics
PubMed: 34529059
DOI: 10.1093/femsle/fnab125 -
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 -
Critical Reviews in Analytical Chemistry 2022Acenocoumarol is an oral anticoagulant medicinal agent is frequently prescribed for the prophylaxis and the management of thromboembolic events. Acenocoumarol is... (Review)
Review
Acenocoumarol is an oral anticoagulant medicinal agent is frequently prescribed for the prophylaxis and the management of thromboembolic events. Acenocoumarol is prescribed in the form of racemic mixture and S- form is a more influential isomer. Acenocoumarol starts quickly with action and absorption, and the effect lasts for 15-20 h. In most patients, the therapeutic prothrombin range is caused 36 h after the primary dose. This review offers a detailed overview of the various analytical methodologies published in the literature from 1976 to uptil now for evaluation acenocoumarol and its combinations in specimens. The present review also stated the chiral analytical methods for the quantification of its enantiomers. A detailed study of the work revealed several analytical methodologies are routinely used for estimation of acenocoumarol includes UV/Vis-Spectrophotometry, liquid chromatography-mass spectrophotometry, high-performance liquid-chromatography, gas chromatography, high-performance thin-layer chromatography, capillary electrophoresis, Fourier-transform infrared spectroscopy and many miscellaneous techniques. Pharmaceutical analysis carried out the prominent task to understand the knowledge of the physicochemical properties of the medicinal agent; since the establishment of a new analytical method is still a challenging task for a research scientist. Thus, the present review will help to research scientist for the development of new analytical methods for the acenocoumarol.
Topics: Acenocoumarol; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Electrophoresis, Capillary; Humans; Pharmaceutical Preparations
PubMed: 32897755
DOI: 10.1080/10408347.2020.1815169 -
Cureus Mar 2023Coronavirus disease 2019 (COVID-19) causes endothelial damage, blood stasis, and an overall state of hypercoagulability. This makes COVID a huge risk factor for venous... (Review)
Review
Coronavirus disease 2019 (COVID-19) causes endothelial damage, blood stasis, and an overall state of hypercoagulability. This makes COVID a huge risk factor for venous thromboembolism (VTE) and arterial thromboembolism (ATE). Twenty percent of COVID-19 patients suffer from coagulation abnormalities like pulmonary embolism, myocardial infarction, stroke, deep vein thrombosis, etc. Ovarian vein thrombosis (OVT) has been previously linked to post-partum period, pregnancy, hypercoagulable state, or malignancy. We analyzed PubMed and Google Scholar databases for research and publications regarding OVT in patients with COVID-19. The search yielded nine case reports. These case reports were found to implicate COVID-associated coagulopathy (CAC) as an additional risk factor for ovarian vein thrombosis (OVT). OVT most commonly presents with abdominal pain and fever, making it difficult to diagnose, owing to the similarity in presentation with multiple other pathologies. OVT can be diagnosed radiologically with ultrasound, magnetic resonance imaging (MRI) scan, or CT scan with IV contrast. CT has been used as the modality of choice for diagnosing OVT. Although rare, OVT can cause life-endangering complications by extension of thrombus into systemic veins or pulmonary artery embolization. Therefore, early diagnosis and treatment are vital. There is no official guideline for the treatment of OVT post-COVID. However, the literature supports the use of apixaban or enoxaparin/acenocoumarol.
PubMed: 37090373
DOI: 10.7759/cureus.36437 -
The Journal of the Association of... Oct 2023Warfarin has been the most extensively used oral anticoagulant (OAC) in medical settings for over 60 years. Its uses, potential adverse effects, and methods for... (Review)
Review
Warfarin has been the most extensively used oral anticoagulant (OAC) in medical settings for over 60 years. Its uses, potential adverse effects, and methods for reversing its effects have been firmly established, rendering it a routine medication in medical settings where most professionals feel at ease employing it. Compared to other vitamin K antagonists (VKAs), such as acenocoumarol, warfarin offers benefits like diminished prothrombin time (PT) assays leading to enhanced oral anticoagulation. Observations over the past few years have seen the inclusion of novel/direct OACs (NOACs/DOACs) in the anticoagulant armamentarium. Although DOACs have several advantages, warfarin still has an important role in subsets of patients where DOACs are contraindicated, not well-tolerated, or cannot afford DOACs due to higher costs. Moreover, there are patient profiles where warfarin is still considered a superior choice compared to DOACs, such as age group of >75 years, kidney failure with creatinine clearance (CrCl) below 30 mL/minute, and prosthetic mechanical valve replacement. Precise management of the international normalized ratio (INR) is crucial for the effectiveness of warfarin treatment. INR monitoring is the major concern in the Indian context due to the lack of laboratories for standardized measurement. Adopting strategies such as point-of-care INR monitoring devices and anticoagulation clinics can help to improve clinical outcomes with warfarin therapy. The present review provides a critical overview of the role of warfarin therapy in the current OAC arsenal and strategies for improving therapeutic control and patient adherence. : Nair T. Critical Appraisal on the Role of Warfarin in the Current Era. J Assoc Physicians India 2023;71(10):31-36.
Topics: Humans; Warfarin; Anticoagulants; International Normalized Ratio; Drug Monitoring
PubMed: 38716521
DOI: 10.59556/japi.71.0378 -
The American Journal of the Medical... Dec 2022Vitamin K antagonists (VKA) are the most widely used anticoagulants for the prevention of thrombotic events. Several renal adverse effects have been associated with the...
BACKGROUND
Vitamin K antagonists (VKA) are the most widely used anticoagulants for the prevention of thrombotic events. Several renal adverse effects have been associated with the use of VKA. The main aim of our study was to explore the association between international normalized ratio (INR) levels and microscopic hematuria in patients with VKA.
METHODS
We performed a cross-sectional study of patients treated with VKA that attended the outpatient clinic for routine INR control. A simple urinalysis was performed on the day of the INR control and the precise number of red cells in the urine sediment was quantified. Demographic data, kidney function tests, comorbidities, anticoagulant dose and concomitant treatment were registered.
RESULTS
A total of 337 patients were included with median INR levels of 2.6 (IQR 2.1-3.3). 11.9% of the patients presented microscopic hematuria (≥14 RBCs/µl). There was a significant correlation between INR levels and the number of red blood cells in the urine sediment (r = 0.201, p = 0.024). In the univariate analysis, microscopic hematuria was associated with having an INR >3.5 (19% vs. 10.2%, p = 0.046), bacteriuria (15.2% vs. 3.6%, p = 0.015), leukocyturia (14.8% vs. 6.6%, p = 0.026), hypertension (16.2% vs. 9.5%, p = 0.053), and the use of renin-angiotensin system (RAS) blockers (6.9% vs. 17.2%, p = 0.004). Multivariate logistic regression showed an association between microscopic hematuria and RAS blockade (OR 0.38, CI 95% 0.163-0.886, p = 0.025), independent from INR levels, hypertension, leukocyturia or bacteriuria.
CONCLUSIONS
INR overdose was significantly associated with the presence of microscopic hematuria. RAS blockade is an independent protective factor for the presence of microscopic hematuria in anticoagulated patients.
Topics: Humans; Vitamin K; Hematuria; Cross-Sectional Studies; Bacteriuria; Anticoagulants; International Normalized Ratio; Fibrinolytic Agents; Hypertension
PubMed: 35850278
DOI: 10.1016/j.amjms.2022.07.002 -
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