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Journal of Medicine and Life 2015Vitamin K antagonists (VKA), such as warfarin and acenocoumarol, are widely used for the prevention and treatment of thromboembolic diseases and they are some of the...
RATIONALE
Vitamin K antagonists (VKA), such as warfarin and acenocoumarol, are widely used for the prevention and treatment of thromboembolic diseases and they are some of the most commonly prescribed types of medications. They are characterized by narrow therapeutic indices and inter-individual or intra-individual variability in response to the treatment.
OBJECTIVE
to establish the influence of several genetic factors on VKA efficacy and adverse reactions.
METHODS AND RESULTS
The metabolism of VKA differs depending on their chemical structure: indandiones derivatives (fluindione) or coumarin derivatives (acenocoumarol, phenprocoumon or warfarin). They are mostly metabolized in hepatocytes via a monooxygenase, cytochrome P450 2C9 (CYP2C9), resulting in inactive products. The gene encoding CYP2C9 is polymorphic, its genetic variants being associated with differences in the enzymatic activity of CYP2C9. The most important in terms of their frequency in the general population are CYP2C9*2 and CYP2C9*3. Both alleles are associated with a marked decrease in CYP2C9 enzyme activity. VK epoxide reductase (VKOR) is an enzyme with an important role in VK metabolism. Various polymorphisms in the VKORC1 gene have been described. VKORC1*2 haplotype seems to be the most important in relation to the variability in response to VKA.
DISCUSSIONS
Various studies have shown a relationship between the genotype and the mean warfarin maintenance dosing: in patients carrying 2C9*1/*2 alleles, the dose is reduced by 18-40% in patients carrying 2C9*2/*2 alleles, by 21-49% in patients carrying 2C9*1/*3 alleles. The A allele of the c.-1639G>A polymorphism in the VKORC1 gene is associated with the need for a lower dose of acenocoumarol in patients on anticoagulant therapy.
ABBREVIATIONS
SNP = Single Nucleotide Polymorphism, VKA = vitamin K antagonists, C1 - VKORC1 = vitamin K epoxide reductase complex subunit, INR = International Normalized Ratio.
Topics: Administration, Oral; Anticoagulants; Cytochrome P-450 CYP2C9; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Vitamin K; Vitamin K Epoxide Reductases
PubMed: 25866574
DOI: No ID Found -
European Journal of Clinical... Dec 2016The purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs). (Clinical Trial)
Clinical Trial
PURPOSE
The purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs).
METHODS
We selected patients on VKAs of two Dutch anticoagulation clinics who initiated treatment with a statin between 2009 and 2013. Patients who initiated or stopped concomitant drugs that interact with VKAs or were hospitalised during follow-up were excluded. The VKA dosage (mg/day) after statin initiation was compared with the last VKA dosage before the statin was started. Immediate and long-term differences in VKA dosage (at 6 and 12 weeks) were calculated with a paired student t test.
RESULTS
Four hundred thirty-five phenprocoumon users (mean age 70 years, 60 % men) and 303 acenocoumarol users (mean age 69 years, 58 % men) were included. After start of statin use, the immediate phenprocoumon dosage was 0.02 mg/day (95 % CI, 0.00 to 0.03) lower. At 6 and 12 weeks, these phenprocoumon dosages were 0.03 (95 % CI, 0.01 to 0.05) and 0.07 mg/day (95 % CI, 0.04 to 0.09) lower as compared with the dosage before first statin use. In acenocoumarol users, VKA dosage was 0.04 mg/day (95%CI, 0.01 to 0.07) (immediate effect), 0.10 (95 % CI, 0.03 to 0.16) (at 6 weeks), and 0.11 mg/day (95 % CI, 0.04 to 0.18) (after 12 weeks) lower.
CONCLUSIONS
Initiation of statin treatment was associated with an immediate and long-term minor although statistically significant decrease in VKA dosage in both phenprocoumon and acenocoumarol users, which suggests that statins may have anticoagulant properties.
Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Vitamin K
PubMed: 27709253
DOI: 10.1007/s00228-016-2138-6 -
Hellenic Journal of Cardiology : HJC =... 2021To estimate the incidence of hemorrhagic events in patients with atrial fibrillation (AF) treated with acenocoumarol, and the management cost of those requiring...
BACKGROUND
To estimate the incidence of hemorrhagic events in patients with atrial fibrillation (AF) treated with acenocoumarol, and the management cost of those requiring hospitalization in Greece.
METHODS
A nationwide telephone survey was conducted between December 2017 and January 2018, to identify cardiologists who treat AF patients with acenocoumarol. A total of 300 cardiologists were selected and reported the number of AF acenocoumarol-treated patients during the past 12 months and the number of those who experienced a hemorrhagic event. The hospital charges to sickness fund and the cost of resource utilization of AF patients hospitalized between January 2013 and June 2017 at a tertiary hospital in Athens due to acenocoumarol-related bleedings were retrieved.
RESULTS
Out of 48,255 AF patients, 12,633 (26.2%) were treated with acenocoumarol. In all, 5.1% of patients experienced a hemorrhagic event with the incidence of bleeding requiring hospitalization being 1.7%. The most common bleeding site was the gastrointestinal system (51.5%). The mean (95% CI) management cost per bleeding event requiring hospitalization was €1,202 (€1,058-€1,420). The higher cost was that of intracranial bleeding €3,887 (€2,700-€5,046). The expected annual economic burden for the management of bleedings related to acenocoumarol and requiring hospitalization was estimated at €1,463,955.
CONCLUSIONS
The incidence of bleeding events in AF acenocoumarol-treated patients in Greece as well as the estimated annual economic burden for the management of bleeding events requiring hospitalization, emphasize the need to comply with the current guidelines and to optimize therapeutic strategies for the management of AF side effects with oral anticoagulants, particularly in patients with high bleeding risk.
Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Greece; Hospitalization; Humans; Incidence; Retrospective Studies; Stroke
PubMed: 32683128
DOI: 10.1016/j.hjc.2020.06.013 -
Clinical and Applied... 2019Warfarin and acenocoumarol are used in various cardiovascular disorders to improve the prognosis of patients with thromboembolic disease. However, there is a lack of...
Warfarin and acenocoumarol are used in various cardiovascular disorders to improve the prognosis of patients with thromboembolic disease. However, there is a lack of substantial efficacy and safety data on antithrombotic prophylaxis in several countries, particularly in Latin America. The aim of this study was to provide information about the efficacy of anticoagulants in Chilean patients. Data were collected from databases of the Western Metropolitan Health Service, Santiago, Chile. We identified 6280 records of patients receiving anticoagulant treatment. The three most common diagnoses were rhythm disorder (43.7%), venous thrombosis (22%), and valvular prosthesis (10.7%). The majority of patients (98.5%) received acenocoumarol while 1.5% of patients received warfarin, at weekly therapeutic doses of 13.6 mg and 30.4 mg, respectively. For total diagnoses, the median time in the therapeutic range was 50%. However, better results, 66.7%, were observed when a telemedicine strategy was used only in Santiago Province. Our findings emphasize that in Chile, where the number of patients receiving anticoagulant treatment increases every year, telemedicine, by committed teams, improves the use of oral anticoagulants and is able to increase quality indicators of anticoagulant treatment care.
Topics: Aged; Anticoagulants; Chile; Coumarins; Female; Humans; Male; Retrospective Studies; Telemedicine; Warfarin
PubMed: 30880431
DOI: 10.1177/1076029619834342 -
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 -
Biopharmaceutics & Drug Disposition Jan 2017Vitamin K antagonists (VKAs) remain the oral anticoagulant of choice in venous thromboembolic disease. These drugs are characterized by a large inter-individual...
Vitamin K antagonists (VKAs) remain the oral anticoagulant of choice in venous thromboembolic disease. These drugs are characterized by a large inter-individual variability requiring frequent dose tailoring. Genetic polymorphisms for cytochrome CYP2C9 and VKORC1 explain some of the variability, especially in warfarin and acenocoumarol responses. The aim of this study was to assess, in cell models, the role of ABC transporters in the intestinal transfer of the main coumarin derivatives (warfarin, acenocoumarol) and indanedione derivatives (phenindione, fluindione). The results show a basal to apical polarized transport for fluindione, phenindione and acenocoumarol only. Experimental studies using specific inhibitors of transport protein demonstrate the implication of MRPs and BCRP proteins and to a lesser extent P-gp. Warfarin and acenocoumarol seem to be poor inhibitors of MRPs protein, whereas fluindione and phenindione have a slight or no effect. The regulation of the expression of ABC transporters by exposure to VKAs was also investigated in Caco-2 cells. The expression of mRNA P-gp, MRP1, MRP2 and BCRP was weakly or not modified after 24 h of VKAs exposure. In conclusion, the intestinal transfer of indanedione derivatives and acenocoumarol could be influenced by transport proteins of the ABC superfamily. Coumarin derivatives are poor inhibitors of these proteins and AVKs have a slight effect on the mRNA ABC transporter expression level. Copyright © 2016 John Wiley & Sons, Ltd.
Topics: ATP-Binding Cassette Transporters; Animals; Biological Transport; Caco-2 Cells; Dogs; Humans; Madin Darby Canine Kidney Cells; Vitamin K
PubMed: 27925230
DOI: 10.1002/bdd.2055 -
International Journal of Clinical... Feb 2015Studies investigating drug-induced anaemia are relatively scarce and mostly related to specific drugs or patients with specific pathologies. (Review)
Review
BACKGROUND
Studies investigating drug-induced anaemia are relatively scarce and mostly related to specific drugs or patients with specific pathologies.
OBJECTIVE
To analyse all reports of suspected drug-induced anaemias recorded in the National Pharmacovigilance Database of the Italian Medicines Agency.
METHOD
The cases of suspected drug-induced anaemias analysed were those retrieved from the Italian National Pharmacovigilance Database from January 2001 to December 2013.
RESULTS
The active substances involved were 375 in 3,305 reports of drug-induced anaemia; of these, 72 % were reported as serious. In 35 % of the reports patients were in polytherapy. In 24.3 % of the cases relevant DDIs were identified. We found a PRR value of 57.29 for peginterferon alfa-2a, of 12.57 for ribavirin, of 13 for flu vaccine for the occurrence of autoimmune haemolytic anaemia. The drugs mostly involved in the cases where the Naranjo causality was probable or possible were acetylsalicylic acid, warfarin, ribavirin, peginterferon alfa-2a, carboplatin and acenocoumarol.
CONCLUSIONS
A possible signal was detected for peginterferon alfa-2a, ribavirin and flu vaccine in the occurrence of autoimmune haemolytic anaemia. A great involvement of clopidogrel, enoxaparin, warfarin, ticlopidine and acetylsalicylic acid in preventable DDI-induced anaemia was detected, highlighting a poor awareness among healthcare providers on this issue.
Topics: Adverse Drug Reaction Reporting Systems; Anemia; Anticoagulants; Antineoplastic Agents; Antiviral Agents; Databases, Factual; Drug Interactions; Humans; Italy; Pharmacovigilance
PubMed: 25515616
DOI: 10.1007/s11096-014-0054-3 -
Anales Del Sistema Sanitario de Navarra Aug 2020Infection caused by SARS-CoV-2 (COVID-19) is associated with an increased risk of thromboembolic disease. So-me authors recommend anticoagulation at therapeutic doses...
Infection caused by SARS-CoV-2 (COVID-19) is associated with an increased risk of thromboembolic disease. So-me authors recommend anticoagulation at therapeutic doses for, at least, the most severely ill patients; this practice is not free of risks, which is why only thromboembolic prophylaxis is recommended by other consensuses. In the case of previously anticoagulated patients, changing the oral anticoagulant for a low molecular weight heparin (LMWH) is generally recommended. We present the cases of two patients admitted due to COVID-19, without serious clinical data, in whom anticoagulation (acenocoumarol and rivaroxaban, respectively) was replaced by LMWH at therapeutic doses, both presenting abdominal bleeding. This type of bleeding is an infrequent complication in anticoagulated patients, but the concurrence of two cases in a short period of time in the context of the COVID-19 pandemic leads us to consider that there is not yet any clear evidence on therapeutic anticoagulation in SARS-CoV-2 infection.
Topics: Abdomen; Acenocoumarol; Aged, 80 and over; Anticoagulants; Betacoronavirus; COVID-19; Coronavirus Infections; Female; Hematoma; Heparin, Low-Molecular-Weight; Humans; Pandemics; Pneumonia, Viral; Rivaroxaban; SARS-CoV-2; Venous Thromboembolism
PubMed: 32865189
DOI: 10.23938/ASSN.0884 -
Farmacia Hospitalaria : Organo Oficial... Mar 2019To analyze the interaction between acenocoumarol and levofloxacin in the elderly. We also assessed how hypoalbuminemia affects international normalized ratio variation. (Observational Study)
Observational Study
OBJECTIVE
To analyze the interaction between acenocoumarol and levofloxacin in the elderly. We also assessed how hypoalbuminemia affects international normalized ratio variation.
METHOD
Retrospective study carried on elderly institutionalized patients who were prescribed levofloxacin concomitantly with acenocoumarol. International normalized ratio variation during levofloxacin treatment was analyzed with the t-Student test. Correlation between albuminemia and international normalized ratio variation was calculated using Pearson´s correlation coefficient.
RESULTS
The mean international normalized ratio previous to treatment with levofloxacin was 2.5 (standard deviation: 0.6) and during treatment it was 4.7 (standard deviation: 1.9) (p < 0.05). In 54.3% of the cases, the international normalized ratio value was equal to or greater than 4.5. Not linear association between albuminemia and international normalized ratio increase was found using Pearson´s test (R = -0.16).
CONCLUSIONS
In more than half of the occasions international normalized ratio raised to clinically rellevant values (≥ 4.5). No influence of hypoalbuminemia in the increase in international normalized ratio was shown.
Topics: Acenocoumarol; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anticoagulants; Blood Coagulation; Drug Interactions; Female; Humans; Institutionalization; International Normalized Ratio; Levofloxacin; Male; Middle Aged; Retrospective Studies; Serum Albumin
PubMed: 30848177
DOI: 10.7399/fh.11111 -
BMC Public Health Jul 2021Assessment health literacy in people with cardiovascular health problems would facilitate the development of appropriate health strategies for the care and reduction of...
BACKGROUND
Assessment health literacy in people with cardiovascular health problems would facilitate the development of appropriate health strategies for the care and reduction of complications associated with oral anticoagulation therapy.
AIM
To evaluate the relationship between health literacy and health and treatment outcomes (concordance with oral anticoagulants, Normalized Ratio control and occurrence of complications) in patients with cardiovascular pathology.
METHODS
Observational, analytic and cross-sectional study carried out on 252 patients with cardiovascular pathology (atrial fibrillation, flutter or valve prosthesis), aged 50-85 years, accessing primary care services in Valencia (Spain) in 2018-2019. Variables referring to anticoagulant treatment with vitamin K antagonists (years of treatment, adequate control, polypharmacy and occurrence of complications, among others) and health literacy (Health Literacy Questionnaire) were analysed.
RESULTS
All dimensions of health literacy were significantly related to the level of education (p < 0.02), social class (p < 0.02), an adequate control of acenocoumarol (p < 0.001), frequentation of health services (p < 0.001), information by patients to health professionals about anticoagulant treatment (p < 0.03), emergency care visits (p < 0.001) and unscheduled hospital admissions (p < 0.001).
CONCLUSION
Health literacy has a relevant influence on the adequate self-management of anticoagulation treatment and the frequency of complications. The different dimensions that comprise health literacy play an important role, but the "social health support" dimension seems to be essential for such optimal self-management.
TRIAL REGISTRATION
ACC-ACE-2016-01. Registration date: December 2015.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Health Literacy; Humans; Social Determinants of Health; Spain; Treatment Outcome
PubMed: 34243749
DOI: 10.1186/s12889-021-11259-w