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Journal of Comparative Effectiveness... Oct 2019To compare the risk of stroke, systemic thromboembolism and bleeding, in patients initiating apixaban or acenocoumarol for the treatment of nonvalvular atrial... (Observational Study)
Observational Study
Patient characteristics and stroke and bleeding events in nonvalvular atrial fibrillation patients treated with apixaban and vitamin K antagonists: a Spanish real-world study.
To compare the risk of stroke, systemic thromboembolism and bleeding, in patients initiating apixaban or acenocoumarol for the treatment of nonvalvular atrial fibrillation. An observational, retrospective study was performed using medical records of patients who initiated apixaban or acenocoumarol between 2015 and 2017. Propensity score matching was used to match patients; stroke, systemic thromboembolism, major and minor bleeding events were compared between the matched patients. Patients who were prescribed apixaban had a lower rate of systemic embolism/stroke (hazard ratio [HR] = 0.54; 95% CI: 0.38-0.78; p = 0.001), minor bleeding (HR = 0.64; 95% CI: 0.52-0.79; p < 0.001) and major bleeding (HR = 0.51; 95% CI: 0.37-0.72; p < 0.001). Patients prescribed apixaban for the treatment of nonvalvular atrial fibrillation had lower rates of thromboembolic events and minor/major bleeding than patients on acenocoumarol.
Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Stroke; Vitamin K
PubMed: 31333045
DOI: 10.2217/cer-2019-0079 -
EXCLI Journal 2019
PubMed: 31611751
DOI: 10.17179/excli2019-1714 -
Oncotarget Jun 2018Oral anticoagulants (OAs) are the recommended drugs to prevent cardiovascular events and recurrence in patients with atrial fibrillation (AF) and cardioembolic stroke.... (Review)
Review
Oral anticoagulants (OAs) are the recommended drugs to prevent cardiovascular events and recurrence in patients with atrial fibrillation (AF) and cardioembolic stroke. We conducted a literature search to review the current state of OAs pharmacogenomics, focusing on Genome Wide Association Studies (GWAs) in patients treated with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). VKAs: Warfarin, acenocoumarol, fluindione and phenprocoumon have long been used, but their interindividual variability and narrow therapeutic/safety ratio makes their dosage difficult. GWAs have been useful in finding genetic variants associated with VKAs response. The main genes involved in VKAs pharmacogenetics are: and Variants in these genes have been included in pharmacogenetic algorithms to predict the VKAs dose individually in each patient depending on their genotype and clinical variables. DOACs: Dabigatran, apixaban, rivaroxaban and edoxaban have been approved for patients with AF. They have stable pharmacokinetics and do not require routine blood checks, thus avoiding most of the drawbacks of VKAs. Except for a GWAs performed in patients treated with dabigatran, there is no Genome Wide pharmacogenomics data for DOACs. Pharmacogenomics could be useful to predict the better clinical response and avoid adverse events in patients treated with anticoagulants, identifying the most appropriate anticoagulant drug for each patient. Current pharmacogenomics data show that the polymorphisms affecting VKAs or DOACs are different, concluding that personalized medicine based on pharmacogenomics could be possible. However, more studies are required to implement personalized medicine in clinical practice with OA and based on pharmacogenetics of DOACs.
PubMed: 30018749
DOI: 10.18632/oncotarget.25579 -
Indian Journal of Thoracic and... Oct 2019Vitamin K antagonists (VKAs), such as warfarin and acenocoumarol, exert their anti-coagulant effect by inhibiting the subunit 1 of vitamin K epoxide reductase complex...
PURPOSE
Vitamin K antagonists (VKAs), such as warfarin and acenocoumarol, exert their anti-coagulant effect by inhibiting the subunit 1 of vitamin K epoxide reductase complex (VKORC1). CYP2C9 is a hepatic drug-metabolizing enzyme in the CYP450 superfamily and is the primary metabolizing enzyme of warfarin. Three single nucleotide polymorphisms, two in the CYP2C9 gene, namely CYP2C9*2 and CYP2C9*3, and one in the VKORC1 gene (c.- 1639G > A, rs9923231), have been identified to reduce VKA metabolism and enhance their anti-coagulation effect. The purpose of this study is to evaluate the prevalence of CYP2C9 and VKORC1 polymorphism in Indians receiving VKA-based anti-coagulation after valve surgery and to evaluate the usefulness of genetic information in managing VKA-based anti-coagulation.
METHODS
In the current prospective observational study, 150 patients who underwent heart valve surgery and had stable INR were genotyped for VKORC1 (- 1639 G > A), CYP2C9*2, and CYP2C9*3. The VKA dosage was estimated from published algorithms and compared to the clinically stabilized dosage.
RESULTS
Out of 150 patients, 101 (67.33%) were on warfarin and 49 (32.66%) were on acenocoumarol. Majority of the patients, the 83 in warfarin group and the 40 in acenocoumarol group, had a wild CYP2C9 diplotype. The rest had a mutant (CYP2C9*2 or CYP2C9*3) diplotype. Similarly, 67 patients in the warfarin group and 35 patients in the acenocoumarol group had wild type (G/G) of VKORC1 genotype. The rest had a mutant (G/A or A/A) VKORC1 genotype. In the warfarin group, based on the genotype, 51.5% of the patients were extensive or normal metabolizers, and 47.4% of the patients were intermediate metabolizers of VKAs. In the acenocoumarol group, 61.2% of the patients were extensive or normal metabolizers, and 38.8% of the patients were intermediate metabolizers. Individually, alleles of VKORC1 (- 1639 G > A), CYP2C9*2, and CYP2C9*3 had mean dosage reduction effect on VKA dosage, which co-related to the clinically stabilized dosages ( < 0.0001). Among the VKORC1 (- 1639 G > A) cohort, the reduction in warfarin mean weekly dosage was 13.48 mg as compared to the wild-type category ( < 0.0001) and similarly, the reduction in the mean weekly acenocoumarol dose was 6.07 mg ( < 0.03) as compared to the wild type after adjusting for age, gender, and body mass index.
CONCLUSION
Single nucleotide polymorphism in the CYP2C9 gene and in the VKORC1 gene is present in nearly 40% of Indian patients. VKORC1 (- 1639 G > A), CYP2C9*2, and CYP2C9*3 genotypes have significant dosage-lowering effects on VKA-based anti-coagulation therapy. The trend in estimated dosages of VKAs co-related to that of observed the clinically stabilized dosage in the cohort. The pharmacogenomic calculators used in this study tend to overestimate the VKA dosages as compared to clinical dosage due to the limitations in the algorithms and in our study. A new algorithm based on a larger dataset capturing the vast genetic variability across the Indian population and relevant clinical factors could provide better results.
PubMed: 33061049
DOI: 10.1007/s12055-019-00812-3 -
Annals of the Rheumatic Diseases May 2021Vitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may...
OBJECTIVES
Vitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may represent a modifiable risk factor. A genetic variant in a vitamin K-dependent protein that is an essential inhibitor for cartilage calcification, matrix Gla protein (MGP), was associated with an increased risk for OA. Vitamin K antagonist anticoagulants (VKAs), such as warfarin and acenocoumarol, act as anticoagulants through inhibition of vitamin K-dependent blood coagulation proteins. VKAs likely also affect the functioning of other vitamin K-dependent proteins such as MGP.
METHODS
We investigated the effect of acenocoumarol usage on progression and incidence of radiographic OA in 3494 participants of the Rotterdam Study cohort. We also examined the effect of and single nucleotide variants on this association.
RESULTS
Acenocoumarol usage was associated with an increased risk of OA incidence and progression (OR=2.50, 95% CI=1.94-3.20), both for knee (OR=2.34, 95% CI=1.67-3.22) and hip OA (OR=2.74, 95% CI=1.82-4.11). Among acenocoumarol users, carriers of the high ) expression haplotype together with the OA risk allele (rs1800801-T) had an increased risk of OA incidence and progression (OR=4.18, 95% CI=2.69-6.50), while this relationship was not present in non-users of that group (OR=1.01, 95% CI=0.78-1.33).
CONCLUSIONS
These findings support the importance of vitamin K and vitamin K-dependent proteins, as MGP, in the pathogenesis of OA. Additionally, these results may have direct implications for the clinical prevention of OA, supporting the consideration of direct oral anticoagulants in favour of VKAs.
Topics: 4-Hydroxycoumarins; Acenocoumarol; Aged; Alleles; Anticoagulants; Calcium-Binding Proteins; Disease Progression; Extracellular Matrix Proteins; Female; Humans; Incidence; Indenes; Male; Middle Aged; Osteoarthritis; Polymorphism, Single Nucleotide; Prospective Studies; Vitamin K; Vitamin K Epoxide Reductases; Matrix Gla Protein
PubMed: 34412027
DOI: 10.1136/annrheumdis-2020-219483 -
British Journal of Clinical Pharmacology Feb 2021Acenocoumarol is a vitamin-K antagonist (VKA) primarily used in certain countries (e.g. India, Netherlands, Spain). The half-life of acenocoumarol is similar to that of...
Clinical outcomes of nonvitamin K oral anticoagulants and acenocoumarol for stroke prevention in contemporary practice: A population-based propensity-weighted cohort study.
AIMS
Acenocoumarol is a vitamin-K antagonist (VKA) primarily used in certain countries (e.g. India, Netherlands, Spain). The half-life of acenocoumarol is similar to that of non-VKA oral anticoagulants (NOAC), unlike warfarin, and this could affect comparative effectiveness and safety (CES). However, data on CES for NOAC come almost exclusively from studies using warfarin as the comparator. We aimed to assess outcomes of NOAC and acenocoumarol in people with non-valvular atrial fibrillation (NVAF) in real-world clinical practice.
METHODS
This is a population-based retrospective cohort study. All new users of oral anticoagulants from November 2011 to December 2015 with NVAF were included (n = 41,560). Data were obtained by linking several health electronic records of the Valencia region, Spain. Incidence rates were estimated. We used the inverse probability of treatment weighted Cox analysis to control for indication bias when assessing the risk of effectiveness and safety outcomes for each NOAC compared with acenocoumarol. Several sensitivity analyses were performed.
RESULTS
We did not find differences in the risk of mortality, ischaemic stroke or any gastrointestinal bleeding. However, we did find a decreased risk of intracranial haemorrhage for dabigatran (HR: 0.34, 95% CI 0.20-0.56) and rivaroxaban (HR: 0.55, 95% CI 0.35-0.85) as compared to acenocoumarol. In subanalyses, apixaban showed a higher risk of ischaemic stroke in high-risk persons (≥75 years and CHA2DS2-VASC score ≥ 2).
CONCLUSIONS
No differences in clinical outcomes were found between NOAC and acenocoumarol overall, although dabigatran and rivaroxaban showed a lower risk of intracranial haemorrhage. Findings on the potential inferiority of specific NOAC in high-risk subgroups should be studied further.
Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Dabigatran; Humans; India; Netherlands; Retrospective Studies; Rivaroxaban; Spain; Stroke
PubMed: 32530052
DOI: 10.1111/bcp.14430 -
Medicina (Kaunas, Lithuania) Apr 2021Patients with heart failure (HF) often present with non-valvular atrial fibrillation and require oral anticoagulation with coumarin anticoagulants such as...
Clinical Impact of the Time in Therapeutic Range on Early Hospital Readmission in Patients with Acute Heart Failure Treated with Oral Anticoagulation in Internal Medicine.
Patients with heart failure (HF) often present with non-valvular atrial fibrillation and require oral anticoagulation with coumarin anticoagulants such as acenocoumarol. The objective of this study was to evaluate the relationship between time in therapeutic range (TTR) and the risk of early readmission. A retrospective descriptive study was carried out on hospitalized patients with a diagnosis of HF between 2014 and 2018 who had adverse effects due to oral anticoagulation with acenocoumarol (underdosing, overdosing, or hemorrhage). Clinical, analytical, therapeutic, and prognostic variables were collected. TTR is defined as the duration of time in which the patient's International Normalized Ratio (INR) values were within a desired range. Early readmission was defined as readmission within 30 days after hospital discharge. Patients were divided into two groups depending on whether or not they had a TTR less than 60% (TTR < 60%) over the 6 months prior to the adverse event. In the cohort of 304 patients, the mean age was 82 years, 59.9% of the patients were female, and 54.6% had a TTR < 60%. Patients with TTR < 60% had a higher HAS-BLED score (4.04 vs. 2.59; < 0.001) and INR (6 vs. 5.31; < 0.05) but lower hemoglobin (11.67 vs. 12.22 g/dL; < 0.05). TTR < 60% was associated with early readmission after multivariate analysis (OR: 2.05 (CI 95%: 1.16-3.61)). They also had a higher percentage of hemorrhagic events and in-hospital mortality but without reaching statistical significance. Patients with HF and adverse events due to acenocoumarol often have poor INR control, which is independently associated with a higher risk of early readmission.
Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Heart Failure; Humans; Male; Patient Readmission; Retrospective Studies; Treatment Outcome; Vitamin K
PubMed: 33918627
DOI: 10.3390/medicina57040365 -
Clinical Cardiology Oct 2017Thromboembolic complications can be life-threatening during atrial fibrillation (AF) catheter ablation. The aim of our study was to evaluate the safety and efficacy of... (Comparative Study)
Comparative Study
BACKGROUND
Thromboembolic complications can be life-threatening during atrial fibrillation (AF) catheter ablation. The aim of our study was to evaluate the safety and efficacy of continuous treatment using direct oral anticoagulants (DOACs) as an alternative to uninterrupted acenocoumarol for periprocedural anticoagulation.
HYPOTHESIS
Continuous treatment with DOACs has similar safety and efficacy compared to acenocoumarol.
METHODS
We enrolled 474 patients (mean age, 58 years; 68.4% male) undergoing AF catheter ablation between June 2013 and December 2016. All patients were equally assigned to take acenocoumarol (group 1, 136 patients) or DOACs (group 2, 338 patients) for ≥2 months before the procedure. We compared thromboembolic and bleeding complications between the 2 groups.
RESULTS
Our analysis showed no significant difference in major and minor complications between the 2 patient groups. Specifically, 3 of 136 patients (2.2%) using uninterrupted acenocoumarol had a major complication (1 patient [0.7%] had transient ischemic attack resolved 8 hours later, 1 [0.7%] had pericardial tamponade, and 1 [0.7%] had a subcapsular renal hematoma) and 2 patients (1.4%) had minor complications (1 [0.7%] pseudoaneurysm and 1 [0.7%] groin hematoma). In group 2, 1 of 338 patients (0.3%) had a major complication (transient ischemic attack). In the same group, 7 patients (2.1%) had a minor complication (1 patient [0.3%] presented with pseudoaneurysm, 4 [1.2%] with pericardial effusion <1 cm, 1 [0.3%] femoral arteriovenous fistula between the femoral artery and femoral vein, and 1 [0.7%] groin hematoma).
CONCLUSIONS
DOACs and acenocoumarol have similar safety and effectiveness regarding thromboembolic complications prevention without increasing bleeding complications.
Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Catheter Ablation; Dabigatran; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Pyrazoles; Pyridones; Registries; Risk Factors; Rivaroxaban; Thromboembolism; Time Factors; Treatment Outcome
PubMed: 28561951
DOI: 10.1002/clc.22734 -
Archives of Medical Science : AMS 2022infection is accepted as the leading cause of chronic gastritis, ulcer disease and gastric cancer, with an important impact on health care burden, especially in...
INTRODUCTION
infection is accepted as the leading cause of chronic gastritis, ulcer disease and gastric cancer, with an important impact on health care burden, especially in countries with a high prevalence of infection. The aim of the study was to investigate the influence of infection, medication, associated medical conditions or social habits on endoscopic ulcer occurrence in the compensated type 2 diabetic population.
MATERIAL AND METHODS
Two hundred and sixty type 2 diabetic patients investigated on endoscopy (57 patients with peptic ulcer and 203 controls) with a complete set of biopsies, demographic and medical data were enrolled.
RESULTS
On univariate regression analysis, infection (42.1% vs. 35.5%, = 0.359) or a history of peptic ulcer (61.4% vs. 61.6%, = 0.981) was not a predictor for ulcer on endoscopy in the diabetic population, and heartburn was more frequent in diabetics without ulcer (21.2% vs. 8.8%, = 0.033). Anemia was the best predictor for ulcer on endoscopy in both diabetics with ( < 0.001, OR = 4.77, 95% CI: 2.02-11.28) and without ( = 0.027, OR = 2.76, 95% CI: 1.10-6.91) chronic proton pump inhibitor (PPI) therapy. In diabetic patients on PPI more than 1 month anticoagulants - acenocoumarol or low-weight molecular heparin ( = 0.038, OR = 2.37, 95% CI: 1.04-5.40), low-dose aspirin 75-125 mg/day ( = 0.029, OR = 2.61, 95% CI: 1.08-6.28) and alcohol consumption ( = 0.015, OR = 2.70, 95% CI: 1.19-6.13) were predictors for ulcer on endoscopy.
CONCLUSIONS
In diabetic patients, anemia is the most important predictor for ulcer on endoscopy, but not or digestive symptoms, while low-dose aspirin or anticoagulant therapy and alcohol consumption are the most important predictors for ulcer in diabetics on chronic proton pump inhibitor therapy.
PubMed: 35154524
DOI: 10.5114/aoms/93098 -
International Journal of Environmental... May 2021The use of vitamin K antagonists (VKAs) in non-valvular atrial fibrillation (NVAF) is complicated due to the narrow therapeutic margin they present and their...
The use of vitamin K antagonists (VKAs) in non-valvular atrial fibrillation (NVAF) is complicated due to the narrow therapeutic margin they present and their unpredictable dose-response relationship. Most studies are based on warfarin, with the results being extrapolated to acenocoumarol. However, studies comparing the two treatments in terms of the degree of anticoagulation control are scarce, justifying the present study. Main factors associated with poor control of time in therapeutic range (TTR) of anticoagulated patients are also studied. Cross-sectional study, with real-world data from patients treated in primary care (PC). Data were obtained from the System for the Improvement of Research in PC (SIDIAP) database, covering 60,978 NVAF-anticoagulated patients from 287 PC centres in 2018. Descriptive statistics were derived, and odds ratios were estimated by multivariate logistic regression. 41,430 patients were considered: 93% were being treated with acenocoumarol and 7% with warfarin. There was no difference in poor control of TTR between the two types of VKA treatment, acenocoumarol and warfarin (38.9 vs. 38.4; = 0.610). Poor anticoagulation control was mainly associated with advanced alcoholism (OR = 1.38), liver failure (OR = 1.37) and intracranial haemorrhage (OR = 1.35) as well as female sex, age < 60 years, cardiovascular history, diabetes mellitus and other variables. There is no association between poor anticoagulation control and the type of VKA treatment administered. Factors associated with poor control of TTR must be considered in clinical practice to improve control and decision-making.
Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Female; Humans; Middle Aged; Primary Health Care; Stroke; Warfarin
PubMed: 34073370
DOI: 10.3390/ijerph18115700