-
Journal of the American College of... Sep 2014Chronic oral anticoagulant therapy is recommended (class I) in patients with mechanical heart valves and in patients with atrial fibrillation with a CHA2DS2-VASc... (Review)
Review
Chronic oral anticoagulant therapy is recommended (class I) in patients with mechanical heart valves and in patients with atrial fibrillation with a CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack or thromboembolism, Vascular disease, Age 65 to 74 years, Sex category) score ≥1. When these patients undergo percutaneous coronary intervention with stenting, treatment with aspirin and a P2Y12 receptor inhibitor also becomes indicated. Before 2014, guidelines recommended the use of triple therapy (vitamin K antagonists, aspirin, and clopidogrel) for these patients. However, major bleeding is increasingly recognized as the Achilles' heel of the triple therapy regimen. Lately, various studies have investigated this topic, including a prospective randomized trial, and the evidence for adding aspirin to the regimen of vitamin K antagonists and clopidogrel seems to be weakened. In this group of patients, the challenge is finding the optimal equilibrium to prevent thromboembolic events, such as stent thrombosis and thromboembolic stroke, without increasing bleeding risk.
Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Humans; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Ticlopidine; Vitamin K
PubMed: 25236521
DOI: 10.1016/j.jacc.2014.06.1193 -
Revista Portuguesa de Cardiologia :... Apr 2012Oral anticoagulant therapy is changing. In several clinical settings, warfarin and acenocumarol remain the standard oral anticoagulants. However, in view of the... (Review)
Review
Oral anticoagulant therapy is changing. In several clinical settings, warfarin and acenocumarol remain the standard oral anticoagulants. However, in view of the limitations of vitamin K antagonists, resulting from its slow onset of pharmacological action, its narrow therapeutic window, its variable metabolism, dependent of citochrome P450, its multiple pharmacological and food interactions and its potential risk for hemorrhagic complications, the last years have witnessed the emergence of new pharmacological groups in oral anticoagulant therapy, that can overcome these problems. At present, pharmacological investigation is focused in the development of new non-peptide molecules, which can inhibit essential moments of the coagulation system (thrombin and factor Xa), with a predictable and consistent pharmacodynamic and pharmacokinetic pattern, administered orally. Of these compounds, three of them (dabigatran, rivaroxaban and apixaban) already have defined (or to be defined) therapeutic indications, built on large interventional phase III studies, while many others are in less advanced development phases. This review summarizes and discusses the pharmacology of warfarin/acenocumarol and of the new direct thrombin and factor Xa inhibitors, exemplifying similarities and stressing differences that help us justify out therapeutic options.
Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Humans; Thrombin; Vitamin K; Warfarin
PubMed: 22541030
DOI: 10.1016/S0870-2551(12)70034-3 -
Molecules (Basel, Switzerland) Mar 2021Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some... (Comparative Study)
Comparative Study Observational Study
Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, < 0.001). A higher prevalence of TiTR (<60%, <65%, or <70%) was found in acenocoumarol users than in warfarin ones ( < 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin.
Topics: Acenocoumarol; Aged; Anticoagulants; Blood Coagulation; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Retrospective Studies; Venous Thromboembolism; Warfarin
PubMed: 33800767
DOI: 10.3390/molecules26051425 -
Cardiology Journal 2017The SAMe-TT2R2 (sex female, age, medical history, treatment, tobacco use, race) score was developed in patients with atrial fibrillation (AF) on warfarin. The present... (Comparative Study)
Comparative Study
BACKGROUND
The SAMe-TT2R2 (sex female, age, medical history, treatment, tobacco use, race) score was developed in patients with atrial fibrillation (AF) on warfarin. The present study aimed to 1) compare the anticoagulation quality and management of AF patients treated with warfarin with those on acenocoumarol and 2) optimize the SAMe-TT2R2 score to detect AF patients at high risk of unstable anticoagulation with acenocoumarol and warfarin.
METHODS
In a single-center retrospective study, 320 patients with AF, including 15 (5%) after valve replacement, aged 40-82 (median 70) years, including 203 (63%) receiving acenocoumarol and 117 (37%) treated with warfarin, were studied. The SAMe-TT2R2 score was modified based on the candidate factors retrieved from univariate regression and assessed using the receiver operating curves (ROC).
RESULTS
A median SAMe-TT2R2 score was 2 (1-3). Proportions of patients with ≥ 2 points and 0-1 points in the SAMe-TT2R2 score who had the time in therapeutic range (TTR) ≤ 70% were similar (61 [67%] vs. 63 [56%], p = 0.11). A modified score, involving medical history (myocardial infarction [MI] and chronic obstructive pulmonary disease [COPD], 1 point), statin treatment (1 point) and tobacco use (2 points) had a higher area under the curve (AUC) in patients on acenocoumarol compared to SAMe- TT2R2 (0.66; 95% confidence interval 0.58-0.73 vs. 0.56; 0.48-0.64, p = 0.042); ≥ 1 point indicated TTR > 70% with a sensitivity and specificity of 61% and 63%, respectively.
CONCLUSIONS
The SAMe-TT2R2 score is less effective in predicting unstable anticoagulation with acenocoumarol versus warfarin. Adding statin use and highlighting COPD and previous MI increases a predictive value of this score for acenocoumarol.
Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Area Under Curve; Atrial Fibrillation; Blood Coagulation; Blood Coagulation Tests; Clinical Decision-Making; Decision Support Techniques; Drug Monitoring; Female; Humans; Male; Middle Aged; Poland; Predictive Value of Tests; ROC Curve; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Warfarin
PubMed: 28353307
DOI: 10.5603/CJ.a2017.0038 -
Clinical Pharmacokinetics Jan 2012Vitamin K epoxide reductase complex, subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) polymorphisms are taken into account when predicting a safe oral dose of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVE
Vitamin K epoxide reductase complex, subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) polymorphisms are taken into account when predicting a safe oral dose of coumarin anticoagulant therapy, but little is known about the effects of genetic predictors on the response to fluindione and acenocoumarol. The aims of this study were to characterize the relationship between fluindione and acenocoumarol concentrations and the international normalized ratio (INR) response, and to identify genetic predictors that are important for dose individualization.
METHODS
Fluindione concentrations, S- and R-acenocoumarol concentrations, the INR and genotype data from healthy subjects were used to develop a population pharmacokinetic-pharmacodynamic model in Monolix software. Twenty-four White healthy subjects were enrolled in the pharmacogenetic study. The study was an open-label, randomized, two-period cross-over study. The subjects received two doses of an oral anticoagulant: 20 mg of fluindione (period A) or 4 mg of acenocoumarol (period B). The pharmacokinetics and pharmacodynamics were studied from day 2 to day 3.
RESULTS
A two-compartment model with a first-order input model was selected as the base model for the two drugs. The pharmacodynamic response was best described by an indirect action model with S-acenocoumarol concentrations and fluindione concentrations as the only exposure predictors of the INR response. Three covariates (CYP2C9 genotype, VKORC1 genotype and body weight) were identified as important predictors for the pharmacokinetic-pharmacodynamic model of S-acenocoumarol, and four covariates (CYP2C9 genotype, VKORC1 genotype, CYP1A2 phenotype and body weight) were identified as predictors for the pharmacokinetic-pharmacodynamic model of fluindione. Because some previous studies have shown a dose-response relationship between smoking exposure and the CYP1A2 phenotype, it was also noted that smokers have greater CYP1A2 activity.
CONCLUSION
During initiation of therapy, CYP2C9 and VKORC1 genetic polymorphisms are important predictors of fluindione and acenocoumarol pharmacokinetic-pharmacodynamic responses. Our result suggests that it is important to take the CYP1A2 phenotype into account to improve individualization of fluindione therapy, in addition to genetic factors.
Topics: Acenocoumarol; Adult; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Body Weight; Cross-Over Studies; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2C9; Female; Genotype; Humans; International Normalized Ratio; Male; Mixed Function Oxygenases; Models, Biological; Phenindione; Polymorphism, Genetic; Smoking; Vitamin K Epoxide Reductases
PubMed: 22149257
DOI: 10.2165/11595560-000000000-00000 -
Reumatologia Clinica 2020We present the case of a 73-year-old man with IgA vasculitis after administration of acenocoumarol, confirmed by anatomopathological study. He had cutaneous, joint and...
We present the case of a 73-year-old man with IgA vasculitis after administration of acenocoumarol, confirmed by anatomopathological study. He had cutaneous, joint and renal involvement. With the reintroduction of the drug, the clinical manifestations worsened. They were completely resolved with its suspension, without additional maintenance treatment.
Topics: Acenocoumarol; Aged; Anticoagulants; Humans; IgA Vasculitis; Male
PubMed: 30031735
DOI: 10.1016/j.reuma.2018.05.006 -
Journal of Thrombosis and Haemostasis :... May 2012Previous studies have provided contradictory results regarding the interaction between the CYP2C9 and VKORC1 genotypes affecting various outcome measures.
BACKGROUND
Previous studies have provided contradictory results regarding the interaction between the CYP2C9 and VKORC1 genotypes affecting various outcome measures.
OBJECTIVES
We aimed to provide a definite answer regarding the question whether there exists a gene-gene interaction between the CYP2C9 and VKORC1 genotypes affecting the anticoagulant effect of phenprocoumon and acenocoumarol.
PATIENTS/METHODS
The EU-PACT cohort dataset, which contains data on 624 phenprocoumon and 471 acenocoumarol patients, was used. Patient characteristics, pharmacogenetic data, International Normalized Ratios (INRs) and dosages were available. We investigated whether there was an interaction between the CYP2C9 and VKORC1 genotypes affecting the maintenance dose, time to severe over-anticoagulation and time to achieve stability during the first 180 days of phenprocoumon and acenocoumarol therapy, in addition to the effect of the separate genotypes. The interaction effect was investigated by adding the product term of the CYP2C9 and VKORC1 genotype classes for four different commonly used CYP2C9 classifications to the linear regression model - for the outcome measure maintenance dose - or to the Cox regression models - for the outcome measures time to severe over-anticoagulation and time to achieve stability.
RESULTS
No significant interactions - all P-values above 0.23 for phenprocoumon and 0.30 for acenocoumarol - were observed for all outcome measures.
CONCLUSIONS
There are no interactions between the CYP2C9 and VKORC1 genotypes affecting the maintenance dose, time to severe over-anticoagulation and time to achieve stability for phenprocoumon and acenocoumarol.
Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Blood Coagulation; Cytochrome P-450 CYP2C9; Drug Monitoring; Female; Genotype; Humans; International Normalized Ratio; Linear Models; Male; Middle Aged; Mixed Function Oxygenases; Netherlands; Pharmacogenetics; Phenotype; Phenprocoumon; Proportional Hazards Models; Vitamin K Epoxide Reductases
PubMed: 22409277
DOI: 10.1111/j.1538-7836.2012.04694.x -
Frontiers in Endocrinology 2018Both vitamin D and K2 are involved in a number of metabolic processes, including bone metabolism; however, associations between the vitamins are not fully understood....
OBJECTIVE
Both vitamin D and K2 are involved in a number of metabolic processes, including bone metabolism; however, associations between the vitamins are not fully understood. The aim of the study was to evaluate serum concentrations of 25-hydroxyvitamin D [25(OH)D] in adult patients receiving long-term acenocoumarol (AC) treatment.
PARTICIPANTS AND METHODS
In this cross-sectional study, 58 Caucasian patients (31 women, 27 men) with a median age of 65 years receiving long-term AC therapy were evaluated and compared with 35 age- and gender-matched healthy controls. The AC treatment was used due to recurrent venous thromboembolism (34.5%), atrial fibrillation (31%), or mechanical heart valve prostheses (34.5%). Medical records and a questionnaire were used to obtain information about chronic diseases, smoking habits, and the duration of therapy and weekly dose of AC. Anthropometric measurements were performed, and serum concentration of 25(OH)D and total alkaline phosphatase (ALP) activity were measured.
RESULTS
Among the 58 patients receiving long-term AC treatment, a high proportion (46.6%) demonstrated significant vitamin D deficiency with concentrations of 25(OH)D lower than 20 ng/mL. The median concentration of 25(OH)D in subjects receiving AC was significantly lower compared to the control group [20.4 (17.4; 26.1) vs. 28.2 (24; 32.7); < 0.001]. No differences were found between women and men receiving AC therapy. In patients receiving AC, a negative correlation was found between the concentration of 25(OH)D and the weekly dose of AC ( = -0.337, = 0.01). Patients with concentrations of 25(OH)D < 20 ng/mL were found to have a significantly higher median dose of AC, compared to those with concentrations of 25(OH)D ≥ 20 ng/mL [21 (17; 31) vs. 17 (12; 28); = 0.045].
CONCLUSION
In conclusion, treatment with AC is associated with low 25-hydroxyvitamin D levels, although the path leading to this phenomenon is not entirely clear. Long-term administration of AC in adults may increase the risk of chronic vitamin D deficiency, thus, effective supplementation of vitamin D in these individuals needs careful consideration.
PubMed: 29780360
DOI: 10.3389/fendo.2018.00226 -
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 -
Acta Haematologica 1993We present the case of a woman undergoing treatment with acenocoumarol for deep vein thrombosis, who maintained an international normalized ratio (INR) of between 2.5...
We present the case of a woman undergoing treatment with acenocoumarol for deep vein thrombosis, who maintained an international normalized ratio (INR) of between 2.5 and 4 for 2 months. Seven days after the introduction of amoxycillin (500 mg/8 h) for a probable respiratory infection, the patient developed spontaneous bruising, with an INR of 7.1. Treatment with amoxycillin was discontinued, and 3 weeks later the INR had returned to previous values. In this case, the increase in the INR value with associated bruising after the addition of amoxycillin suggests a drug interaction between acenocoumarol and amoxycillin, other possible causes having been eliminated.
Topics: Acenocoumarol; Aged; Aged, 80 and over; Amoxicillin; Drug Interactions; Drug Therapy, Combination; Female; Humans; Postoperative Complications; Respiratory Tract Infections; Thrombophlebitis; Time Factors
PubMed: 8140860
DOI: 10.1159/000204457