acenocoumarol and Atrial-Fibrillation

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Dose-Response Relationship, Drug; Drug Substitution; Factor Xa Inhibitors; Hemoptysis; Humans; International Normalized Ratio; Lung; Male; Pyrazoles; Pyridones; Thrombophilia; Tomography, X-Ray Computed

Nonvalvular atrial fibrillation (NVAF) is a risk factor for ischemic stroke and systemic embolism. New oral anticoagulants are currently available. The objective of this study was to assess the incremental cost-utility ratio (ICUR) for apixaban vs. acenocoumarol in patients treated in Chile's public health system.. We assessed cost-utility from the payer perspective with a lifetime Markov model. Epidemiologic characteristics, costs, and utilities were obtained from a Chilean cohort; data were completed with information from international literature.. Incremental costs when using apixaban vs. acenocoumarol over a lifetime are CH$2,108,600 with an incremental effectiveness of 0.173 years of life gained (YLG) and 0.182 quality-adjusted life-year (QALY). The ICUR of apixaban vs. acenocoumarol was CH$12,188,439 per YLG and CH$11,585,714 per QALY. One to 3 times gross domestic product (GDP) per capita threshold is acceptable based on World Health Organization (WHO) norms. Chilean GDP per capita was CH$7,797,021 in 2013. The sensitivity analysis shows that these results are sensitive to the ischemic stroke risk with apixaban, and the intracranial hemorrhage risk due to the use of acenocoumarol.. The use of apixaban in patients with NVAF in moderate-to-high risk of stroke is cost-effective, considering the payment threshold suggested by WHO.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Chile; Cost-Benefit Analysis; Epidemiologic Studies; Factor Xa Inhibitors; Female; Humans; Latin America; Male; Pyrazoles; Pyridones; Risk; Stroke

The periprocedural management of patients receiving chronic therapy with oral anticoagulants (OACs), including vitamin K antagonists (VKAs) such as warfarin and direct OACs (DOACs), is a common clinical problem. The optimal perioperative management of patients receiving chronic OAC therapy is anchored on four key principles: (i) risk stratification of patient-related and procedure-related risks of thrombosis and bleeding; (ii) the clinical consequences of a thrombotic or bleeding event; (iii) discontinuation and reinitiation of OAC therapy on the basis of the pharmacokinetic properties of each agent; and (iv) whether aggressive management such as the use of periprocedural heparin bridging has advantages for the prevention of postoperative thromboembolism at the cost of a possible increase in bleeding risk. Recent data from randomized trials in patients receiving VKAs undergoing pacemaker/defibrillator implantation or using heparin bridging therapy for elective procedures or surgeries can now inform best practice. There are also emerging data on periprocedural outcomes in the DOAC trials for patients with non-valvular atrial fibrillation. This review summarizes the evidence for the periprocedural management of patients receiving chronic OAC therapy, focusing on recent randomized trials and large outcome studies, to address three key clinical scenarios: (i) can OAC therapy be safely continued for minor procedures or surgeries; (ii) if therapy with VKAs (especially warfarin) needs to be temporarily interrupted for an elective procedure/surgery, is heparin bridging necessary; and (iii) what is the optimal periprocedural management of the DOACs? In answering these questions, we aim to provide updated clinical guidance for the periprocedural management of patients receiving VKA or DOAC therapy, including the use of heparin bridging.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Aortic Valve; Atrial Fibrillation; Elective Surgical Procedures; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Perioperative Care; Phenprocoumon; Prothrombin; Randomized Controlled Trials as Topic; Societies, Medical; Thromboembolism; Thrombosis; United States; Vitamin K; Warfarin

Anticoagulant treatment is required for the treatment and prevention of thromboembolic disorders. Vitamin K antagonists are commonly used oral anticoagulants worldwide. Acenocoumarol is mono-coumarin derivative with racemic mixture of R (+) and S (-) enantiomers. Efficacy and safety of acenocoumarol has been evaluated in atrial fibrillation, cardiac valve replacement, after myocardial infarction, treatment of deep vein thrombosis, after major surgeries and after critical illness requiring prolonged hospitalization. Acenocoumarol is effective and safe in all age groups. It offers an advantage over warfarin in terms of better stability of anti-coagulant effect. Due to its economic advantage acenocoumarol may be suitable oral anticoagulant for long term use in countries like India.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; India; Mixed Function Oxygenases; Myocardial Infarction; Thromboembolism; Treatment Outcome; Vitamin K

Coumarin anticoagulants (acenocoumarol, phenprocoumon, and warfarin) are generally used for the prevention of stroke in patients with atrial fibrillation or for the therapy and prevention of venous thromboembolism. However, the safe use of coumarin anticoagulants is restricted by a narrow therapeutic window and large interindividual dosing variations. Some studies found that the effectiveness and safety of coumarin anticoagulants therapy were increased by pharmacogenetic-guided dosing algorithms, while others found no significant effect of genotype-guided therapy.. Four electronic databases were searched from January 1, 2000, to March 1, 2014, for randomized controlled trials of patients who received coumarin anticoagulants according to genotype-guided dosing algorithms. The primary outcome was the percentage of time that the international normalized ratio (INR) was within the normal range (2.0-3.0). Secondary outcomes included major bleeding events, thromboembolic events, and INR ≥4 events.. Eight studies satisfied the inclusion and exclusion criteria. Genotype-guided dosing of coumarin anticoagulants improved the percentage of time within the therapeutic INR range (95% confidence interval [CI], 0.02-0.28; P = .02; I(2) = 70%). Subgroup analysis was performed after dividing the nongenotype-guided group into a standard-dose group (95% CI, 0.14-0.49; P = .0004; I(2) = 50%) and a clinical variables-guided dosing algorithm group (95% CI, -0.07-0.15; P = .48; I(2) = 34%). There is a statistically significant reduction in numbers of secondary outcomes (INR ≥4 events, major bleeding events, and thromboembolic events; 95% CI, 0.79-1.00; P = .04). Subgroup analysis of secondary outcomes showed no significant difference between genotype-guided dosing and clinical variables-guided dosing (95% CI, 0.84-1.10; P = .57; I(2) = 11%), but genotype-guided dosing reduced secondary outcomes compared with standard dosing (95% CI, 0.62-0.92; P = .006; I(2) = 0%).. This meta-analysis showed that genotype-guided dosing increased the effectiveness and safety of coumarin therapy compared with standard dosing but did not have advantages compared with clinical variables-guided dosing.

Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Dose-Response Relationship, Drug; Genotype; Humans; International Normalized Ratio; Pharmacogenetics; Phenprocoumon; Randomized Controlled Trials as Topic; Stroke; Venous Thromboembolism; Warfarin

Amiodarone-induced thyrotoxicosis (AIT) is a common clinical disorder that may be life threatening and whose clinical manifestations and response to treatment may vary among patients.. We present three patients treated with amiodarone for atrial fibrillation who developed AIT at least 36 months after beginning the treatment. Thyrotoxicosis worsened the underlying cardiac disorders and was resistant to treatment based on the combination of dexamethasone 8-12 mg/day i.v., thioamides 45 mg/day p.o., beta blockers and potassium perchlorate at doses of 800 to 1000 mg per day p.o. Two of the patients attained sustained euthyroidism after 12 and 32 days of combined treatment, while the third required total thyroidectomy.. The combination of thioamides with potassium perchlorate is an appropriate form of therapy for AIT in patients resistant to thioamides. The use of this combination should be evaluated in patients with mixed AIT or AIT of unclear etiology.

Topics: Acenocoumarol; Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Algorithms; Amiodarone; Atrial Fibrillation; Cardiovascular Agents; Comorbidity; Dexamethasone; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pacemaker, Artificial; Perchlorates; Potassium Compounds; Thioamides; Thyroid Hormones; Thyroidectomy; Thyrotoxicosis; Thyrotropin

Anticoagulant therapy is used for stroke prevention and proved to be effective and safe in the long term. The study aims to analyse the cost-effectiveness relationship of using of direct-acting oral anticoagulants vs vitamin K antagonists to prevent ischaemic stroke in patients with nonvalvular atrial fibrillation, including all the active ingredients marketed in Spain, prescribed for 2 years in the Primary Care service of the Institut Català de la Salut.. Population-based cohort study, in which the cost of the 2 treatment groups will be evaluated. Direct costs (pharmacy, primary care, emergency and hospitalization) and indirect costs (lost productivity) will be included from a social perspective. Effectiveness (assessed as the occurrence of a health event, the 1 of primary interest being stroke) will be determined, with a 2-year time horizon and a 3% discount rate. The average cost of the 2 groups of drugs will be compared using a regression model to determine the factors with the greatest influence on determining costs. We will carry out a univariate ('one-way') deterministic sensitivity analysis.. We hope to provide relevant information about direct and indirect costs of oral anticoagulants, which, together with aspects of effectiveness and safety, could help shape the consensual decision-making of evaluating bodies.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cost-Benefit Analysis; Factor Xa Inhibitors; Humans; Pragmatic Clinical Trials as Topic; Primary Health Care; Safety; Spain; Stroke; Treatment Outcome; Vitamin K; Warfarin

Non-vitamin K antagonist oral anticoagulants (NOACs) have been proposed as an alternative to vitamin K antagonists (VKA) for atrial fibrillation (AF) patients. Some studies have proposed that well-managed warfarin therapy is still a valid alternative as efficacious as NOACs but the potential impact and absolute effect of NOACs in "real world" optimally management of VKA AF patients is unknown.. To estimate the potential absolute benefit in clinical outcome rates if the optimally anticoagulated "real-world" AF patients with acenocoumarol had been treated with NOACs.. We included 1361 patients stable on acenocoumarol with a time in therapeutic range of 100% for the previous 6months and 6.5years of follow-up. The estimation of clinical events avoided was calculated applying absolute risk reductions, relative risk reductions and hazard ratios from the pivotal clinical trials, relative to acenocoumarol.. Compared to acenocoumarol, the highest estimated event reduction for stroke was seen with dabigatran 150mg, with an estimated reduction of 0.53%/year. For major bleeding, the highest estimated reduction was seen with apixaban (0.88%/year). For mortality, the largest estimated reduction was with dabigatran 150mg (0.75%/year). In net clinical outcome, apixaban had the estimated highest reduction (1.23%/year). All NOACs showed significantly lower rates for intracranial haemorrhage.. In optimally acenocoumarol anticoagulated AF patients, estimated reductions in stroke, bleeding and net clinical outcomes with various NOACs are evident. NOACs would potentially show an improvement even among optimally VKA AF patients.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Mortality; Prospective Studies; Retrospective Studies; Treatment Outcome; Vitamin K

The first-line drugs for the treatment of non-valvular atrial fibrillation (AF) are non-vitamin K antagonist oral anticoagulants (NOACs), which are preferred over vitamin K antagonists (VKAs). There is some evidence that there are dis-crepancies between everyday clinical practice and the guidelines.. The study aimed to compare the characteristics of patients on VKAs, dabigatran, and rivaroxaban in everyday practice (i.e. baseline characteristics, drug doses, risk factors for bleeding and thromboembolic events). Additionally, we assessed the frequency of prescription of different oral anticoagulants (OACs) in recent years.. This study consisted of data from the multicentre CRAFT (MultiCentre expeRience in AFib patients Treated with OAC) study (NCT02987062). This was a retrospective analysis of hospital records of AF patients (hospitalised in the years 2011-2016) treated with VKAs (acenocoumarol, warfarin) and NOACs (dabigatran, rivaroxaban). A total of 3528 patients with non-valvular AF were enrolled in the CRAFT study.. The total cohort consisted of 1973 patients on VKA, 504 patients on dabigatran, and 1051 patients on rivaroxaban. Patients on rivaroxaban were older (70.5 ± 13.1 years) and more often female (47.9%), compared with those on VKAs (67.0 ± 12.8 years, p < 0.001; 35.5%, p < 0.001) and on dabigatran (66.0 ± 13.9 years, p < 0.001; 38.9%, p = 0.001). Among NOACs, patients with persistent and permanent AF were more likely to receive rivaroxaban (54.7% and 73.4%, re-spectively) than dabigatran (45.3%, p < 0.001 and 26.6%, p = 0.002, respectively). Patients on rivaroxaban had higher risk of thromboembolic events (CHA2DS2VASc 3.9 ± 2.0, CHADS2 2.2 ± 1.4) than those on VKAs (3.3 ± 2.0, 1.9 ± 1.3) and on dabigatran (3.1 ± 2.0, 1.8 ± 1.3). Patients on rivaroxaban had also a higher rate of prior major bleeding (11.2%) than those on VKAs (6.7%, p < 0.001) and on dabigatran (7.3%, p = 0.02). Patients on lower doses of dabigatran and rivaroxaban had a significantly higher risk of thromboembolic and bleeding events. Use of VKAs in the year 2011 was reported in over 96% of patients on OACs, but this proportion decreased to 34.6% in 2016. In the last analysed year (2016) AF patients were treated mainly with NOACs - dabigatran (24.2%) and rivaroxaban (41.3%).. The prescription of VKAs declined significantly after the introduction of NOACs. Patients treated with different OACs demonstrated a distinct baseline clinical profile. The highest risk of thromboembolic events and incidence of major bleedings was observed in patients on rivaroxaban, in comparison to patients on VKAs and dabigatran. Among NOACs, patients treated with lower doses of dabigatran and rivaroxaban were older and had a significantly higher risk of thromboembolic and bleeding events.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Thromboembolism; Warfarin

Eating patterns, food intake and type of alimentation vary greatly during the month of ramadan. Furthermore, fasting, which practiced during the month of ramadan, can have an impact on drug's metabolism. These two factors, fasting and eating habits changes during the month of ramadan, may impact acenocoumarol anticoagulant effect, translated by variations of INR values. The aim of our study was to see ramadan fasting effects on INR variations in patients treated by acenocoumarol. A prospective monocentric study was conducted during the ramadan month on fasting outpatients that were treated by acenocoumarol. Baseline INR values (e.i. most recent available value before the month of ramadan) were compared to INR values obtained during the month of ramadan. All patients were monitored for signs of secondary haemorrhagic complications linked to treatment by anti-vitamin K (AVK). Thirty patients were included in the study with a sex ratio 1. Patients mean age was 65 years. Around two thirds of the patients were treated by AVK for atrial fibrillation. The majority of patients (94%) have been treated by AVK for more than a year. Mean INR was significantly higher during the month of ramadan than baseline (3.51 vs 2.52; p< 0.0001). There were also more overdoses during the month of ramadan than baseline (9 vs. 0; p=0.014). The increased INR values highlights the need of a close monitoring of INR values during the month of ramadan, particularly in patients with a high haemorrhagic risk.

Topics: 4-Hydroxycoumarins; Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Fasting; Female; Hemorrhage; Humans; Indenes; Islam; Male; Middle Aged; Tunisia; Vitamin K

Essentials Prospective studies of pharmacogenetic-guided (PG) coumarin dosing produced varying results. EU-PACT acenocoumarol and phenprocoumon trials compared PG and non-PG dosing algorithms. Sub-analysis of EU-PACT identified differences between trial arms across VKORC1-CYP2C9 groups. Adjustment of the PG algorithm might lead to a higher benefit of genotyping.. Background The multicenter, single-blind, randomized EU-PACT trial compared the safety and efficacy of genotype-guided and non-genetic dosing algorithms for acenocoumarol and phenprocoumon in patients with atrial fibrillation or deep vein thrombosis. The trial showed no differences in the primary outcome between the two dosing strategies. Objectives To explore possible reasons for the lack of differences between trial arms by performing a secondary analysis of EU-PACT data in order to evaluate the performance of both dosing algorithms across VKORC1-CYP2C9 genetic subgroups. Patients/Methods Anticoagulation control measured according to an International Normalized Ratio (INR) below (INR of < 2), within (INR of 2-3) and above (INR of > 3) the therapeutic range was compared across VKORC1-CYP2C9 subgroups. Owing to a low number of patients in each subgroup, trials for acenocoumarol and phenprocoumon were combined for analysis. Results Four weeks after therapy initiation, genotype-guided dosing increased the mean percentage of time in the therapeutic INR range (PTIR) in the VKORC1 GG-CYP2C9*1*1 subgroup as compared with the non-genetic dosing (difference of 14.68%, 95% confidence interval [CI] 5.38-23.98). For the VKORC1 AA-CYP2C9*1*1 subgroup, there was a higher risk of under-anticoagulation with the genotype-guided algorithm (difference of 19.9%; 95% CI 11.6-28.2). Twelve weeks after therapy initiation, no statistically significant differences in anticoagulation control between trial arms were noted across the VKORC1-CYP2C9 genetic subgroups. Conclusions EU-PACT genetic-guided dose initiation algorithms for acenocoumarol and phenprocoumon could have predicted the dose overcautiously in the VKORC1 AA-CYP2C9*1*1 subgroup. Adjustment of the genotype-guided algorithm could lead to a higher benefit of genotyping.

Topics: Acenocoumarol; Aged; Algorithms; Anticoagulants; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Data Interpretation, Statistical; Female; Genotype; Humans; International Normalized Ratio; Male; Middle Aged; Pharmacogenetics; Phenprocoumon; Prospective Studies; Single-Blind Method; Treatment Outcome; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases

The aim of the current analysis was to identify independent predictors of the overall clinical outcome of patients with atrial fibrillation (AF), including both stroke/thromboembolism and/or major bleeding. Given the overlap between stroke and bleeding risk factors, a composite risk-stratification score for stroke/thromboembolism or bleeding could potentially be developed.. We used data from the vitamin K antagonist (VKA) arm (n = 2,293; 65% men; mean age 70 ± 9 years) of the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial, which was a multicenter, randomized, open-label noninferiority study that compared fixed-dose idraparinux with VKA in patients with AF. We defined two composite end points: end point 1 was the combination of stroke/thromboembolism or major bleeding; end point 2 was defined as the combination of stroke, systemic or venous embolism, myocardial infarction, cardiovascular death, or major bleeding.. The independent predictors for composite end point 1 were age (P = .014), previous stroke/transient ischemic attack (P = .049), aspirin use (P = .002), and time in therapeutic range (P = .007). For composite end point 2, similar predictors were evident, plus left ventricular dysfunction (P = .011). Based on the regression models, two novel composite risk-prediction scores were developed and were validated externally in a "real-world" cohort of 441 outpatients with AF receiving anticoagulation treatment. Both composite scores 1 and 2 demonstrated numerically higher discriminatory performance (area under the curve [AUC], 0.728; 95% CI, 0.659-0.798 and AUC, 0.707; 95% CI, 0.655-0.758, for end points 1 and 2, respectively) and a positive net reclassification when compared with currently used risk models (CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke or transient ischemic attack], CHA2DS2VASc [cardiac failure or dysfunction, hypertension, age ≥ 75 years [doubled], diabetes, stroke (doubled)-vascular disease, age 65 to 74 years, and sex category (female)], and HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly]), but the differences were not statistically significant.. We have developed and validated two novel composite scores for stroke/thromboembolism/bleeding that offer good discriminatory and predictive performance. However, these composite risk scores did not perform better than the easier and more practical "traditional" stroke and bleeding risk scores that are currently in use, which allow greater practicality and a more personalized balancing of risks.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Area Under Curve; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Middle Aged; Models, Statistical; Oligosaccharides; Regression Analysis; Reproducibility of Results; Risk Factors; Stroke; Warfarin

Due to heightened risk for thromboembolic complications, nonvalvular atrial fibrillation (NVAF) presents an absolute indication for long-term oral anticoagulation therapy. This was an observational, analytical, randomised, one-year clinical study, conducted in the Blood Transfusion Institute Sarajevo, Bosnia & Herzegovina. The aim of this study was to present the oral anticoagulation treatment in terms of International normalised ratio (INR) monitoring and warfarin/acenocoumarol dose titration in 117 patients with NVAF. INR values, the doses of warfarin and acenocoumarol, as well as the tendency and adequacy of their changes were monitored. Percentages of the therapeutic INR values were 51,77% and 53,62%, subtherapeutic 42,84% and 35,86%, and supratherapeutic 5,39% and 10,53% for the warfarin and acenocoumarol treatment, respectively. The average total weekly doses (TWD) which most frequently achieved the therapeutic INR values were 27,89+/-12,34 mg and 20,44+/-9,94 mg, for warfarin and acenocoumarol, respectively. The dose changes with the INR values 1,7 or lower/3,3 or higher were omitted in 13,46% and 15,63%, and with the INR values 1,8-3,2 were noted in 8,62% and 13,48% of all the check-up visits in the warfarin and acenocoumarol group, respectively. The annual dose changes were noted in 24,65% and 31,41%, and the daily dose changes in 74,43% and 73,36% of all the check-up visits of warfarin and acenocoumarol group, respectively. We can conclude that the management of the oral anticoagulation treatment in our country is in accordance with the relevant recommendations, but with the present tendency toward underdosing and unnecessary frequent dose changing.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Bosnia and Herzegovina; Dose-Response Relationship, Drug; Drug Monitoring; Humans; Middle Aged; Monitoring, Ambulatory; Prospective Studies; Retrospective Studies; Warfarin

Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim of this randomised, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists.. Patients with atrial fibrillation at risk for thromboembolism were randomly assigned to receive either subcutaneous idraparinux (2.5 mg weekly) or adjusted-dose vitamin K antagonists (target of an international normalised ratio of 2-3). Assessment of outcome was done blinded to treatment. The primary efficacy outcome was the cumulative incidence of all stroke and systemic embolism. The principal safety outcome was clinically relevant bleeding. Analyses were done by intention to treat; the non-inferiority hazard ratio was set at 1.5. This trial is registered with ClinicalTrials.gov, number NCT00070655.. The trial was stopped after randomisation of 4576 patients (2283 to receive idraparinux, 2293 to receive vitamin K antagonists) and a mean follow-up period of 10.7 (SD 5.4) months because of excess clinically relevant bleeding with idraparinux (346 cases vs 226 cases; 19.7 vs 11.3 per 100 patient-years; p<0.0001). There were 21 instances of intracranial bleeding with idraparinux and nine with vitamin K antagonists (1.1 vs 0.4 per 100 patient-years; p=0.014); elderly patients and those with renal impairment were at greater risk of such complications. There were 18 cases of thromboembolism with idraparinux and 27 cases with vitamin K antagonists (0.9 vs 1.3 per 100 patient-years; hazard ratio 0.71, 95% CI 0.39-1.30; p=0.007), satisfying the non-inferiority criterion. There were 62 deaths with idraparinux and 61 with vitamin K anatagonists (3.2 vs 2.9 per 100 patient-years; p=0.49).. In patients with atrial fibrillation at risk for thromboembolism, long-term treatment with idraparinux was no worse than vitamin K antagonists in terms of efficacy, but caused significantly more bleeding.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Oligosaccharides; Risk Factors; Single-Blind Method; Stroke; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

We checked the feasibility of self-screening for atrial fibrillation (AF) by instructed patients pts and prompt home self-administration of an initial dose of low-molecular weight heparin (LMWH) prior to seeking medical attention.. Pts with persistent AF and low risk of systemic embolisation qualified to elective cardioversion (CV) were the subjects of our interest. All pts were trained to identify AF by palpation of the radial pulse and to self-inject LMWH in case of arrhythmia recurrence. 232 pts (mean age 59.8 +/- 8.6 years) who maintained sinus rhythm (SR) during 4 weeks following successful cardioversion (CV) and correctly recognized AF recurrence and those without episodes of AF were equipped with nadroparine after acenocoumarol discontinuation. Thromboembolic prophylaxis was continued with antiplatelets agents or those no additional risk factors of systemic embolisation were left without medical therapy.. 191 pts had AF recurrence during the mean 2.6 +/- 1.7 years observation period, 172 of them correctly identified AF episode, including 162 who performed LMWH injections at home. 7 pts, who had performed LMWH injections, presented with SR on arrival to hospital, 6 pts had AF1.2 out of 21 pts who failed to identify their AF episodes and 1 pt of those who correctly detected the AF recurrence but failed to perform LMWH self-injection suffered from ischemic stroke (sensitivity 96.1%, specificity 60.4%). No side effects of domiciliary LMWH self-injection were found.. When properly trained, the majority of pts can accurately diagnose AF recurrence and self-inject initial dose of LMWH, what is feasible and may represent an attractive anti-thromboembolic strategy.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Electric Countershock; Feasibility Studies; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Recurrence; Self Administration; Thromboembolism; Treatment Outcome

This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis.. Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated.. We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism.. Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy.. The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Cause of Death; Dose-Response Relationship, Drug; Drug Therapy, Combination; Embolism; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Intracranial Embolism; Male; Middle Aged; Mitral Valve Stenosis; Platelet Aggregation Inhibitors; Proportional Hazards Models; Salicylates; Survival Analysis; Treatment Outcome

Mitral stenosis (MS) in association with atrial fibrillation (AF) is a clinical condition at high risk for systemic thromboembolism. Although oral anticoagulants greatly reduce the incidence of thromboembolism in these patients, the optimal intensity of treatment has never been tested in specific clinical trials, and current recommendations are derived from studies of nonrheumatic AF. In this study we tested the effectiveness of two different intensities. The study design was carried out as an open randomized prospective study in an anticoagulation clinic. We randomized 103 patients with MS and AF to a low (target INR = 2) or moderate (target INR = 3) anticoagulation regimen. The primary end points were systemic thromboembolism, major bleeding and vascular death. During a mean follow-up of 4.5 years, 1 systemic embolism occurred in the low intensity group (0.41 per 100 pt/yrs, CI 0.01-2.3), and 1 minor stroke occurred in the moderate intensity group (0.40 per 100 pt/yrs, CI 0.01-2.3; p = ns). Major bleeding occurred in 8 patients, with 3 in the low intensity (1.25 per 100 pt/yrs) and 5 in the moderate intensity group (2.0 per 100 pt/yrs, Incidence Rate Ratio 0.6, CI 0.1-3.1; p = ns). Total events (systemic embolism, major bleeding and vascular death) occurred in 7 low intensity patients and 8 moderate intensity patients. As expected, minor bleeding was more frequent in the moderate intensity group of patients, who actually had more intense treatment and required closer monitoring of oral anticoagulant treatment. These data suggest that low intensity anticoagulation, as performed in an anticoagulation clinic, is effective and safe in high risk patients with MS and AF.

Topics: Acenocoumarol; Administration, Oral; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Stenosis; Random Allocation; Thromboembolism; Time Factors; Warfarin

Few trials have studied platelet activity during oral anticoagulation and all show a tendency for platelet aggregation to increase. This adverse effect has also been shown in some patients treated with unfractionated heparin, the so-called white clot syndrome. We studied platelet aggregation in patients with atrial fibrillation enrolled in the NASPEAF study and receiving antiaggregant, anticoagulant and both treatments.. 15 healthy control subjects (group C) and 99 patients were enrolled, the latter receiving 4 different antithrombotic regimens for platelet aggregation: group 1, 600 mg of the antiplatelet drug triflusal; group 2, anticoagulation for an INR of 2-3; and both treatments with 2 different levels of anticoagulation, mean INR of 1.85 (group 3) and of 2.15 (group 4). The same amounts of the agonists ADP, arachidonic acid and collagen were used in all tests. For statistical analysis we used the interval in min, from the addition of the agonist to the beginning of aggregation and the % of aggregation at 5 and 8 min.. After arachidonic acid was given, the interval to the beginning of aggregation was shorter in group 2 than in group C: 0.6 +/- 0.21 and 1.1 +/- 1.2, and in both was significantly shorter than in the other three receiving antiplatelet drugs alone: group 1 = 1.58 +/- 1.4 or combined with anticoagulants: group 3 = 1.7 +/- 1.7 and group 4 = 2.4 +/- 2.1. The % of aggregation at 5 min, in groups C, 2, 1, 3 and 4 was respectively 48 +/- 24, 43.2 +/- 19, 29.6 +/- 17, 34.8 +/- 22 and 23.2 +/- 22.5. The data showed significantly increased platelet activity in groups C and 2 compared to groups 1, 3 and 4. Group 3 with a low anticoagulation level (mean INR = 1.85) showed a tendency to greater platelet activity than group 1 and 4 with p value = 0.08.. The antiplatelet drug triflusal alone or combined with a therapeutic level of anticoagulation effectively reduces platelet aggregation and is not influenced by anticoagulant treatment. A low level of anticoagulation (INR < 2) shows a tendency to increase platelet activity.

Topics: Acenocoumarol; Adenosine Diphosphate; Aged; Analysis of Variance; Anticoagulants; Arachidonic Acid; Atrial Fibrillation; Blood Platelets; Collagen; Embolism; Female; Humans; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Salicylates; Time Factors

To know the percentage of patients with nonrheumatic atrial fibrillation treated with anticoagulants as an approach to the effectiveness of the prophylactic treatment of stroke.. Multicenter observational study.. Six primary health centers from Barcelona.. 465 patients with the diagnosed of AF were selected during the second semester of 1996. Patients that had suffered a hemorrhagic stroke, or with mitral stenosis, or with a prosthetic valve, or had hyperthyroidism, or receiving anticoagulant therapy were excluded.. 299 patients (64%) were finally included for the analysis. 15.8% of the patients were treated with acenocoumarin, and 35.4% were treated with aspirin. The percentage of patients treated improved for high risk patients (higher than 50%).. The percentage of patients with nonrheumatic AF treated with acenocoumarin or aspirin is low, and physicians might be reluctant to use them because of bleeding complications, compliance with the treatment, or problems of accessibility.

Topics: Acenocoumarol; Age Factors; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Atrial Fibrillation; Female; Humans; Male; Middle Aged; Patient Compliance; Platelet Aggregation Inhibitors; Primary Health Care; Spain

In Spain, vitamin K antagonists (VKA) remain the standard treatment for the prevention of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF), despite the high risks of suffering adverse effects. The objective of this study was to characterize the profile of VKA-treated patients suffering from stroke/systemic embolism (SE) or major hemorrhagic episodes, their evolution and the actions taken after those episodes.. EVENTHO was an observational multicenter study conducted in 22 Anticoagulation Spanish Units. The study included patients ≥18 years with AF who suffered major hemorrhagic episodes (67.8%) or stroke/SE (32.1%) during 2016 whileon VKA treatment [acenocoumarol (98.2%) or warfarin (1.8%)]. Time in therapeutic range (TTR) was calculated according to the Rosendaal method based on the international normalized ratio (INR) values of the previous 6 months.. The study included 585 patients (median age [range] 82.3 [43.6-96.2] years; 51.1% men; mean [95% confidence interval, CI] CHA. In the sample studied, half of the AF patients who suffered stroke/SE or major hemorrhagic episode had inadequate TTR and, despite this, after hospital discharge, they restarted treatment with VKA. These results highlight the need to evaluate safer and effective therapeutic alternatives in AF patients with poor TTR control after suffering a stroke/SE or major hemorrhagic episode.

Topics: Acenocoumarol; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Male; Stroke; Vitamin K; Warfarin

Several studies have shown that in patients treated with vitamin K antagonists (VKAs) time spent in therapeutic range (TTR) is lower in females than in males. This retrospective study has evaluated a possible association among over-anticoagulation and gender, type and indications to VKAs, TTR and bleeding. Moreover, the decrease of the INR level, after VKAs withdrawal, was considered.. From December 2020 to January 2004, 1230 patients with venous thromboembolism or atrial fibrillation were enrolled. Age, gender, type of VKAs, clinical indications, INR values and bleeding events were recorded. TTR was calculated considering the entire period of treatment.. A total of 1616 and 1759 over-anticoagulation episodes were found in males and females, respectively. The median INR value was 4.5 (4.0-19.04). Thirty-two percent of the patients did not have an overdose throughout the observation period. The median number of over-anticoagulation per year was significantly higher in females (0.39-year) than in males (0.28-year). After 24 h of VKAs withdrawal, INRs were similar in both genders. Logistic regression analysis showed that the episodes of over-anticoagulation per year were associated with females, atrial fibrillation, warfarin therapy, follow-up length longer than 4 years, and TTR <73%, but were not associated to bleeding episodes.. The higher number of over-anticoagulation can explain the lower TTR in females. An excess of anticoagulation is not associated with bleeding events. The recovery of INR performs better when acenocoumarol is used, therefore, in patients who present several episodes of over-anticoagulation, acenocumarolo could replace warfarin.

Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Male; Retrospective Studies; Sex Factors; Vitamin K; Warfarin

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.. 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.. 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).. 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

Atrial fibrillation is a major cause of death and disability due to stroke. Vitamin K antagonist drugs are effective for prevention, but they have a narrow therapeutic range and multiple pharmacological interactions. In recent years, new therapeutic alternatives have been searched to minimize complications. The main objective is to evaluate the risk of gastrointestinal bleeding in anticoagulated patients and compare the classic treatment with new anticoagulants.. We conducted a retrospective cohort study to determine the risk of gastrointestinal bleeding in patients treated with acenocoumarol/dabigatran/rivaroxaban, between 2012 and 2016. We compared the classic with the new anticoagulant group, and a multivariate logistic regression analysis was used to determinate the risk factors of gastrointestinal bleeding.. A total of 1213 patients were selected, 52.7% male patients, a mean age of 72.6 years old (± 14.563). 73.6% had atrial fibrilation. 14.5% of patients used acetylsalicylic acid, and 4% clopidogrel. 67.2% had a high-risk CHADS-2 Score, and 36.9% a high-risk HAS-BLED Score. We determined a 5.6% (68) of gastrointestinal bleeding, without differences according to anticoagulant used. The multivariate model showed a greater risk for digestive hemorrhage in patients with a previous hemorrhagic event (odds ratio [OR] = 2.422 95% confidence interval [CI]: 1.101-5.327) and the concomitant therapy with clopidogrel (OR = 2.373 95% CI: 0.996-5.652).. No differences were found in the risk of gastrointestinal bleeding between the different anticoagulants. A previous gastrointestinal bleeding were considered independent risk factor. The HAS-BLED score should be taken into account to make clinical decisions about to prescribe anticoagulant treatment.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Clopidogrel; Dabigatran; Female; Gastrointestinal Hemorrhage; Humans; Male; Retrospective Studies; Rivaroxaban; Warfarin

Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Female; Humans; Middle Aged; Primary Health Care; Stroke; Warfarin

Vitamin K antagonists (VKA) based oral anticoagulation, is widely used for the prevention and treatment of thromboembolic disease. The major complication of this therapy is bleeding, and sometimes it can occur in unsuspected areas. Spontaneous pectoral hematoma is one of the rare complications due to over anticoagulation by VKA therapy, with only a few cases reported in the literature. Concomitant use of this therapy with commonly used antibiotic, especially in the elderly with multiple comorbidities, can increase the risk of bleeding. Herein, we report a case of a 72-year-old woman under VKA for the treatment of atrial fibrillation, who presented with a spontaneous massive pectoral hematoma, while using antibiotic to treat a respiratory tract infection, who was successfully managed.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Female; Hematoma; Hemorrhage; Humans; Thromboembolism; Vitamin K

The embolization of thrombi formed within the atria can occur in any form of atrial fibrillation (AF), i.e., paroxysmal, persistent, or permanent. Although ischemic stroke is the most frequent embolic event associated with AF, embolization to other sites in the pulmonary and systemic circulations may occasionally occur. To avert the risk of embolization, long-term oral anticoagulation therapy is recommended for all AF patients if the CHA2DS2-VASC score is at least 1 for men and at least 2 for women. Since anticoagulant therapy is associated with an increased risk of bleeding, the choice of oral anticoagulant agent should be made by careful consideration of the benefit-to-risk ratio. The use of a newer class of direct oral anticoagulants (DOACs) as an alternative to the anti-vitamin K (AVK) anticoagulants (warfarin, acenocumarol, etc.) can help mitigate the need for periodic monitoring of International Normalized Ratio (INR) and adverse bleeding events that are commonly associated with the use of AVK anticoagulants. Though the use of DOACs (dabigatran, rivaroxaban, edoxaban, apixaban, etc.) is gaining ground due to their relative safety profile and the low overall cost, quite a few clinicians remain skeptical about their use.. Our objective was to evaluate the risk of thromboembolism, stroke, neuropsychiatric illness, depression, and dementia, in patients with non-valvular atrial fibrillation who have been treated with either acenocumarol or apixaban, as well as to see the inflammatory status (ESR) and levels of fibrinogen. Our team at Municipal Emergency University Hospital, Timisoara, Romania, conducted a retrospective study using the medical records of AF patients who were treated with either apixaban or acenocumarol between 2016-2019. We divided the patients into two groups and compared the groups for the aforementioned outcomes.. AF patients who were prescribed apixaban had a lower rate of stroke and psychiatric illness compared to those on acenocumarol. No significant correlation was found in terms of risk of developing depression or dementia between the groups.. Non-valvular AF patients on apixaban had lower rates of thromboembolic events than the patients on acenocumarol. This article will serve as a reminder of the positive health and financial outcomes of apixaban use, especially to those healthcare systems that are still oblivious to the decrease in economic burden and gain in quality-adjusted life years (QALY) by the long-term use of NOACS/ DOACS instead of the AVK anticoagulants.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Clinical Decision-Making; Female; Hemorrhage; Humans; Incidence; International Normalized Ratio; Male; Middle Aged; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Retrospective Studies; Risk Assessment; Romania; Stroke

Bridging anticoagulation in atrial fibrillation (AF) patients who need to interrupt vitamin K antagonists for procedures is a clinical dilemma. Currently, guidelines recommend clinicians to take the stroke and bleeding risk into consideration, but no clear thresholds are advised. To aid clinical decision making, we aimed to develop a model in which periprocedural bridging therapy is compared with withholding anticoagulation in AF patients, for several bleeding and stroke risk groups.. A model was developed to simulate both a bridge and a non-bridge cohort, using simulated international normalized ratio (INR) values for patients on warfarin, acenocoumarol, and phenprocoumon. For both clinical strategies, stroke and bleeding risks were included and outcomes were stratified by CHA2DS2-VASc or CHADS2 and HAS-BLED groups. Quality-adjusted life expectancy was the main outcome considered. Our analyses show bridging to only be beneficial for patients with HAS-BLED scores equal or lower to 2 and with CHA2DS2-VASc scores of 6 or higher. For patients using acenocoumarol bridging may be beneficial starting at a CHA2DS2-VASc score of 7. Post-procedural time to therapeutic INR has a significant influence on the results: no significant benefit of bridging was found for patients reaching therapeutic INR values within 5 days.. When deciding whether to bridge anticoagulation, clinicians should consider the patient's individual stroke and bleeding risk, while also considering the patient's post-procedural INR management. In practice, only a small subset of patients is expected to benefit from bridging anticoagulation treatment.

Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Computer Simulation; Hemorrhage; Humans; International Normalized Ratio; Markov Chains; Phenprocoumon; Risk Assessment; Stroke; Time-to-Treatment; Warfarin; Withholding Treatment

Calciphylaxis is a syndrome of cutaneous ischaemic necrosis and ulceration due to arteriolar calcification with subsequent thrombosis, which rarely presents in patients without terminal kidney disease. Recently, several reports of coumarins-associated calciphylaxis have stressed the relevance of anticoagulant therapy as an important risk factor for the development of this condition. We report five cases of acenocoumarol-associated, biopsy-proven calciphylaxis in women aged between 64 and 92 years. The drug had been prescribed for atrial fibrillation and was taken without interruption from 14 to 224 months. Lesions were present for months in all cases and were resistant to multiple therapeutic options, but they resolved only with simple wound care measures 6-14 months after changing the anticoagulant therapy.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Calciphylaxis; Deprescriptions; Female; Humans; Middle Aged

The efficacy and safety of oral anticoagulation (OAC) using the vitamin K antagonists (VKA) are closely associated with the quality of anticoagulation, reflected by time in therapeutic range (TTR). The SAMe-TT2R2 is a risk score developed to predict the quality of anticoagulation control among VKA users. To analyse the quality of anticoagulation and its clinical determinants based on different methods in a prospective cohort of atrial fibrillation patients on VKA treatment participating in the multicentre Spanish observational registry FANTASIIA.. Estimated TTR was calculated from Rosendaal, direct method, international normalized ratio variability, and NICE criteria. Time in therapeutic range values were compared for those patients with a SAMe-TT2R2 score 0-2 and >2. One thousand four hundred and seventy patients were analysed (56.4% male, mean age 74.1 ± 9.5 years). Mean TTR was 61.5 ± 25.1 with Rosendaal and 64.7 ± 24.2 with direct method. There was a high correlation between both methods (ρ = 0.805). The prevalence of poor anticoagulation control was 55%. Diabetes mellitus [odds ratio (OR) 1.38; P = 0.008], peripheral artery disease (PAD, OR 1.62; P = 0.048), and HAS-BLED (OR 1.13; P = 0.022) were independently associated with TTR < 70%. SAMe-TT2R2 score 0-2 had a higher mean TTR than patients with SAMe-TT2R2 >2 (P = 0.044), with a specificity of > 90% for predicting TTR < 70%. Patients with TTR < 70% had higher risk of events (21.7 vs. 16.8%; P = 0.021).. In a multicentre prospective registry, 55% of AF patients had poor anticoagulation control with diabetes mellitus, PAD, and HAS-BLED being independently associated with TTR < 70%. A high SAMe-TT2R2 scores had a high specificity for predicting a TTR < 70% as an indicator of poor quality anticoagulation.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Diabetes Mellitus; Female; Humans; International Normalized Ratio; Male; Odds Ratio; Peripheral Arterial Disease; Prevalence; Prospective Studies; Registries; Risk Factors; Spain; Stroke; Vitamin K

The efficacy and tolerability of vitamin K antagonists (VKAs) depends on the quality of anticoagulant control, reflected by the mean time in therapeutic range (TTR) of international normalized ratio 2.0 to 3.0. In the present study, we aimed to investigate the association between TTR and change in TTR (ΔTTR) with the risk of mortality and clinically significant events in a consecutive cohort of atrial fibrillation (AF) patients.. We included 1361 AF patients stable on VKAs (international normalized ratio 2.0-3.0) during at least the previous 6 months. After 6 months of follow-up we recalculated TTR, calculated ΔTTR (ie, the difference between baseline and 6-month TTRs) and investigated the association of both with the risk of mortality and "clinically significant events" (defined as the composite of stroke or systemic embolism, major bleeding, acute coronary syndrome, acute heart failure, and all-cause deaths).. The median ΔTTR at 6 months of entry was 20% (interquartile range 0-34%), 796 (58.5%) patients had a TTR reduction of at least 20%, while 330 (24.2%) had a TTR <65%. During follow-up, 34 (2.5% [4.16% per year]) patients died and 61 (4.5% [7.47% per year]) had a clinically significant event. Median ΔTTR was significantly higher in patients who died (35.5% vs 20%; P = 0.002) or sustained clinically significant events (28% vs 20%; P = 0.022). Based on Cox regression analyses, the overall risk of mortality at 6 months for each decrease point in TTR was 1.02 (95% CI, 1.01-1.04; P = 0.003), and the risk of clinically significant events was 1.01 (95% CI, 1.00-1.03; P = 0.028). Patients with TTR <65% at 6 months had higher risk of mortality (hazard ratio = 2.96; 95% CI, 1.51-5.81; P = 0.002) and clinically significant events (hazard ratio = 1.71; 95% CI, 1.01-2.88; P = 0.046).. Our findings suggest that in AF patients anticoagulated with VKAs, a change in TTR over 6 months (ie, ΔTTR) is an independent risk factor for mortality and clinically significant events. Even in a cohort with good anticoagulation control, the risk for mortality and clinically significant events increases with every point deterioration of TTR.

Topics: Acenocoumarol; Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Heart Failure; Hemorrhage; Humans; International Normalized Ratio; Male; Regression Analysis; Risk Factors; Stroke; Vitamin K

Warfarin-related nephropathy.. Warfarin.. A 31-year-old female, managed with warfarin for rheumatic heart disease with atrial fibrillation.. There were no alternative causes of nephropathy that could have caused the adverse event in this patient.. Shifting the drug from warfarin to acenocoumarol.. Difference in renal elimination between warfarin and acenocoumarol.. Clinicians should be aware of this rare adverse effect of warfarin, and acenocoumarol can be considered as an alternative therapy for this condition.. Further prospectively designed studies are needed to consider acenocoumarol as an alternative therapy in warfarin-related nephropathy.

Topics: Acenocoumarol; Adult; Anticoagulants; Atrial Fibrillation; Female; Humans; Kidney Diseases; Rheumatic Heart Disease; Warfarin

Vascular disease is a frequent comorbidity in atrial fibrillation (AF) patients, resulting in concomitant use of antiplatelet therapy. In the present study, we investigated the incidence and risk of major bleeding, ischaemic stroke, and mortality in a cohort of AF patients taking acenocoumarol plus antiplatelet therapy, in comparison with AF patients taking only acenocoumarol monotherapy.. We consecutively included 1361 "real-world" AF patients stable for at least the previous 6 months on acenocoumarol (INR 2.0-3.0). The primary endpoint was major bleeding defined using the 2005 International Society on Thrombosis and Haemostasis (ISTH) criteria. As secondary endpoints, we analysed ischaemic strokes and all-cause mortality. During follow-up, all adverse events were recorded and compared within patients taking acenocoumarol plus antiplatelet therapy and patients taking only acenocoumarol.. During 6.5 years (IQR 4.3-7.9) of follow-up, there were 250 (2.83%/year) bleeds, 130 (1.47%/year) ischaemic strokes and 511 (6.23%/year) deaths. After multivariate Cox regression analyses, combined antithrombotic therapy was associated with major bleeding (HR 1.40, 95% CI 1.01-1.94; P = .048), but not lower mortality (HR 0.95, 95% CI 0.75-1.21; P = .674) or ischaemic stroke (HR 1.45, 95% CI 0.97-2.17; P = .072).. In AF patients, the risk of bleeding is higher when antiplatelet therapy is combined with acenocoumarol, but the risk of mortality and stroke was not significantly different from that of patients taking only acenocoumarol.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk

We aimed to study potential variables involved in interindividual variability to acenocoumarol (AC) response in order to establish a pharmacogenetic algorithm (PA) that includes clinical and genetic factors to predict adequate AC dose to stabilize anticoagulation in a cohort of Tunisian patients.. Genotyping of the CYP2C9, VKORC1, CYP4F2, and CALU polymorphisms was conducted on 246 patients using PCR-RFLP technique. AC normalized maintenance dose (NMD): ((mean maintenance dose/international normalized ratio (INR)) equilibrium) was calculated. The statistical study was carried out with SPSS V20.. A significant correlation was found between age, BMI, and daily AC dose (r = - 0.397; p < 0.001 and r = 0.215; p = 0.001, respectively). The carriers of mutated alleles CYP2C9*2 or CYP2C9*3 or VKORC1 haplotypes (H1 and H7) were associated with AC hyper-sensibility. After adjustment to potential covariates, these patients presented supra-therapeutic INR during treatment period and needed low AC dose (ORs* = 0.28 [0.06-0.60], p = 0.004; ORs* = 0.12 [0.04-0.05], p < 0.001; ORs* = 0.45 [0.24-0.84], p = 0.01; and ORs* = 0.28 [0.06-0.98], p = 0.049, respectively). However, carriers of VKORC1 haplotypes (H3 and H12) or mutated alleles CYP4F2 (rs2108622) or CALU (rs1043550) tend to resist to treatment, hence long period of therapy initiation, and must be treated with high AC dose (ORs* = 2.67 [81.12-5.91], p = 0.013; ORs* = 8.76 [1.07-76.26], p = 0.019; ORs* = 3.12 [1.01-9.63], p = 0.047; and ORs* = 3.96 [1.41-11.09], p = 0.009, respectively). A final multivariate regression model explained 48.1% of the global interindividual variability in AC dose requirement.. The PA demonstrated that VKORC1 and CYP2C9 polymorphisms contribution was more important than clinical factors. Applying the PA would allow dose adjustment to treat patients in a personalized manner.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Atrial Fibrillation; Black People; Calcium-Binding Proteins; Cytochrome P-450 CYP2C9; Cytochrome P450 Family 4; Female; Genotype; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Polymorphism, Single Nucleotide; Tunisia; Venous Thrombosis; Vitamin K Epoxide Reductases; Young Adult

Polymorphisms in the vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genes increase the bleeding risk in anticoagulated atrial fibrillation (AF) patients. Here, we aimed to investigate whether VKORC1 and CYP2C9 polymorphisms improved the predictive performance for major bleeding using the HAS-BLED score.. We recruited 652 consecutive AF patients stable on vitamin K antagonist (INR 2.0-3.0) during at least the previous 6 months. A baseline venous blood sample was obtained for DNA extraction. We gave an extra point to the HAS-BLED score if the patient was a simultaneous carrier of the VKORC1 and CYP2C9 polymorphisms related to bleeding, and we called this modified score "GEN|HAS-BLED." During a median follow-up of 7.6 years (IQR 5.6-8.0), all major bleeding events were recorded.. During follow-up, 106 (16.2%) patients experienced a major bleeding (2.81%/y; 42 intracranial haemorrhages and 44 gastrointestinal bleeding) and 24 (3.7%) died from major bleeding (0.48%/y). Cox regression analyses demonstrated a significant association between HAS-BLED or GEN|HAS-BLED and major bleeds, both as continuous or categorical scores. Comparison of receiver operating characteristic (ROC) curves shows that original HAS-BLED clinical score had better predictive ability than GEN|HAS-BLED (0.660, 95% CI 0.622-0.696 vs 0.645, 95% CI 0.607-0.682; P = .030). Discrimination and reclassification analyses showed that GEN|HAS-BLED did not improve sensitivity compared with the original score and even showed significant negative reclassification.. Adding pharmacogenetic factors (ie polymorphisms of the VKORC1 and CYP2C9 genes) to the HAS-BLED score does not improve the prediction or discrimination performance for major bleeding.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Female; Gastrointestinal Hemorrhage; Genetic Predisposition to Disease; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Pharmacogenetics; Polymorphism, Genetic; Proportional Hazards Models; Risk Assessment; ROC Curve; Stroke; Vitamin K Epoxide Reductases

Despite the increasing utilization of direct oral anticoagulant (DOAC) prescriptions, vitamin K antagonists (VKAs) remain the treatment of choice for treating and preventing thromboembolic events. The morbidity and mortality of VKAs are partly due to the difficulty of keeping the patient within the therapeutic range. For patients treated by VKA, time in therapeutic range (TTR) is a quality parameter of treatment, widely used in clinical trials but rarely by prescribers. It is well established that its use correlates with the risk of hemorrhage, thrombosis or mortality. We studied this parameter in a cohort of patients to evaluate the quality of their therapeutic follow-up and tried to identify risk factors for low TTR.. The study was made in collaboration with LaboSud Oc Biologie for a duration of 4 months. It included 3387 patients representing 2,4029 INR. We calculated the patients' TTR. The laboratory transmitted to us the sex and age of each patient and the VKA molecule used, the therapeutic range and the specialty of the prescriber. We then analyzed the odds ratio associated with these different factors.. The mean TTR was 68%, close to the TTR recommended by scientific societies. Patient's sex was the only statistically correlated factor, with a worse equilibrium in females taking VKAs (OR=1.22, 95% CI: 1.06-1.39, P=0.00552). Many factors usually correlated with poor equilibrium under VKA have not been studied due to lack of information.. Given the context of economic restriction and the TTR of our cohort close to the recommended 70%, there would be no benefit in terms of safety to prefer DOAC for the patients involved in this study. Regular monitoring of the individual patient's as well as the cohort's TTR should optimize the management of patients receiving VKAs.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Humans; International Normalized Ratio; Male; Middle Aged; Phenindione; Risk Factors; Sex Factors; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

Nonvitamin K antagonist oral anticoagulants (NOACs) have been proposed as an alternative to vitamin K antagonists in atrial fibrillation (AF) patients but the comparative benefits between NOACs and optimally anticoagulated patients is unknown. We estimated the absolute benefit in clinical outcomes rates of real-world effect of NOACs in optimally anticoagulated AF patients with acenocoumarol. We included 1,361 patients stable on acenocoumarol with time in therapeutic range of 100% and 6.5 years of follow-up. Estimation of clinical events avoided was calculated applying hazard ratio, absolute and relative risk reduction from the real-world meta-analysis. Compared with an optimally anticoagulated population, dabigatran 110 mg had the highest estimated stroke reduction (0.97%/year vs 1.47%/year; p = 0.002), and the benefit was higher than in RE-LY trial. For major bleeding, apixaban showed the highest estimated reduction (1.81%/year vs 2.83%/year; p <0.001). For mortality, the largest estimated reduction was with apixaban (2.68%/year). For gastrointestinal bleeding, only apixaban had a significant reduction compared with acenocoumarol (0.69%/year vs 1.10%/year; p = 0.004), and the reduction was significantly higher than in ARISTOTLE trial. All NOACs showed significantly lower rates for intracranial hemorrhage and had a positive Net Clinical Benefit compared with acenocoumarol. Apixaban showed the highest extended estimated Net Clinical Benefit 2.64 (95%CI 2.34 to 2.96). In conclusion, in optimally acenocoumarol anticoagulated AF patients, estimated reductions in all clinical outcomes with various NOACs are evident, with the best effectiveness and safety profile with apixaban. Indeed, the estimated effect with "real world" NOACs would probably be higher than that seen in phase-III clinical trials.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Female; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Pyrazoles; Pyridones; Rivaroxaban; Spain; Stroke

Anticoagulation with vitamin K antagonists continues to be a challenging task given the difficulty of achieving a correct time in therapeutic range (TTR). The SAMeTT. We prospectively included 212 consecutive patients with nonvalvular atrial fibrillation under treatment with acenocoumarol for at least 6 months that were attended in a cardiology outpatient clinic and were categorized as adherent to medication. We carried out a multivariate regression analysis to detect the independent predictive factors of good control. In all patients. A total of 128 (60.4%) patients presented TTR <70% (average TTR = 63.2). We identified body mass index (OR 0.94, 95%CI 0.89-0.99, p=0.032) and regular vitamin K intake (OR 0.53, 95%CI 0.28-0.99, p= 0.046) as independent predictors of poor anticoagulation control. The discriminatory power of a clinical-genetic model derived from our cohort was significantly better compared to the SAMeTT. In our study the SAMeTT

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Body Mass Index; Female; Humans; Male; Models, Genetic; Multivariate Analysis; Prospective Studies; Vitamin K

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.. 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).. 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.. 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; Retrospective Studies; Risk Factors; ROC Curve; Time Factors; Treatment Outcome; Warfarin

Vitamin K antagonists (VKA) are the most widely used anticoagulants in the world. An appropriate management of treated patients is crucial for their efficacy and safety. The prospective, observational, multicenter, inception-cohort FCSA-START Register, a branch of START Register (NCT02219984) included VKA-treated patients managed by centers of Italian Federation of anticoagulation clinics (AC). Baseline patient characteristics and data during treatment were analyzed and compared with those of ISCOAT study, performed by the Federation and published in 1996/7. 5707 naïve patients [53% males, mean age 73.0 years (28.1% >80 years)], 61.6% treated for atrial fibrillation (AF), and 28.0% for venous thromboembolism were included. During the 8906 patient-years (pt-yrs) of observation, 123 patients had major bleeding (MB) (1.38% pt-yrs; fatal: 0.11% pt-yrs), while non-major clinically relevant bleeds were 144 (1.62% pt-yrs). Bleeding was more frequent in elderly (≥70 years; p = 0.04), and during initial 3-month therapy (p = 0.02). Bleeding rate was 2.5% pt-yrs for temporally related INR results <3.0, increasing to 12.5% for INR ≥ 4.5. Thrombotic events were 47 (0.53% pt-yrs; 4 fatal 0.04% pt-yrs). Compared with ISCOAT-1996/7 results, patients older than 80 y are increased from 8 to 28% (p < 0.01), and those treated for AF are increased from 17 to 61%. The quality of anticoagulation control and incidence of MB are not different. However, thrombotic complications fell drastically from 3.5 to 0.53% pt-yrs (p < 0.01), with lower mortality (p = 0.01). VKA-treated patients monitored in Italian AC have good clinical results, with low bleeding and thrombotic complications rates. Important changes in the treated population and improvement in thrombotic complications are detected compared with the ISCOAT-1996/7 study.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Ambulatory Care Facilities; Anticoagulants; Atrial Fibrillation; Chi-Square Distribution; Female; Heart Valve Prosthesis; Hemorrhage; History, 20th Century; History, 21st Century; Humans; Incidence; Italy; Male; Middle Aged; Population Groups; Registries; Risk Factors; Thromboembolism; Vitamin K; Warfarin

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.. Continuous treatment with DOACs has similar safety and efficacy compared to acenocoumarol.. 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.. 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).. 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

The prevalence of atrial fibrillation (AF) has increased over the past years due to aging of the population, and healthcare costs associated with AF reflect a significant financial burden. The aim of this study was to explore predictors for the real-world AF-related in-hospital costs in patients that recently initiated anticoagulation with acenocoumarol or dabigatran.. Predictors for claimed total hospital care costs and cardiology costs in AF patients were explored by using hospital financial claims data from propensity score matched patient groups in a large Dutch community hospital. This study analyzed the total dataset (n = 766) and carried out a secondary analysis for all matched pairs of anticoagulation naïve AF patients (n = 590) by ordinal regression.. Dabigatran was a predictor for significantly lower cardiology and total hospital care costs (Odds Ratio [OR] = 0.43, 95% confidence interval (CI) = 0.33-0.57; and OR = 0.60, 95% CI = 0.46-0.79, respectively). Female gender was a predictor for lower total hospital care costs. Predictors for an increase in total hospital care costs were the occurrence of stroke or systemic embolism, major bleeding, and minor bleeding. The costs predictors were comparable when limiting the analysis to patients that were anticoagulation naïve. Age and CHA. Dabigatran treatment was as a predictor for lower cardiology costs and lower total hospital care costs in AF patients that initiated oral anticoagulation.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiology; Dabigatran; Embolism; Female; Hemorrhage; Hospital Charges; Humans; Male; Middle Aged; Netherlands; Propensity Score; Retrospective Studies; Sex Factors; Stroke

Bleeding risk with vitamin K antagonists (VKAs) is closely related to the quality of anticoagulation in atrial fibrillation (AF) patients, reflected by time in therapeutic range (TTR). Here we compared the discrimination performance of different bleeding risk scores and investigated if adding TTR would improve their predictive value and clinical usefulness. We included 1361 AF patients stables on VKA for at least 6 months. Bleeding risk was assessed by the HAS-BLED, ATRIA, ORBIT and HEMORR

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Risk Assessment; ROC Curve; Time Factors

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Retrospective Studies; Risk Assessment; Stroke; Treatment Outcome

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Electric Countershock; Female; Humans; Male; Middle Aged; Proportional Hazards Models; Risk Assessment; Risk Factors; ROC Curve; Severity of Illness Index; Spain; Stroke; Thromboembolism

Essentials It is unknown if hemophilia patients with atrial fibrillation need anticoagulation. Endogenous thrombin potentials (ETP) in hemophilia patients and patients on coumarins were compared. Severe hemophilia patients had comparable ETP to therapeutic international normalized ratio (INR). In non-severe hemophilia, 33% had higher ETP than therapeutic INR and may need anticoagulation. Click to hear Dr Negrier's perspective on global assays for assessing coagulation SUMMARY: Background It is unknown whether patients with hemophilia A with atrial fibrillation require treatment with vitamin K antagonists (VKAs) to the same extent as the normal population. Objective To compare hemostatic potential in hemophilia patients and patients on VKAs using thrombin generation (TG). Methods In this cross-sectional study, TG, initiated with 1pM tissue factor, was measured in 133 patients with severe (FVIII < 1%, n = 15) and non-severe (FVIII 1-50%, n = 118) hemophilia A, 97 patients on a VKA with an international normalized ratio (INR) ≥ 1.5 and healthy controls. Endogenous thrombin potential (ETP) (nm*min) was compared according to FVIII level (< 1%, 1-19% and 20-50%) with healthy controls and patients with sub-therapeutic INR (1.5-1.9) and therapeutic INR (≥ 2.0). Medians and interquartile ranges (IQRs) were calculated. Results Compared with healthy controls (898 [IQR 803-1004]), both hemophilia patients and patients on VKAs had lower median ETPs at 304 (196-449) and 176 (100-250), respectively. ETP was quite similar in severe hemophilia patients (185 [116-307]) and patients with a therapeutic INR (156 [90-225]). Compared with patients with therapeutic INR, ETP in patients with FVIII 1-19% and patients with FVIII 20-50% was higher at 296 (203-430) and 397 (219-632), respectively. All patients with therapeutic INR had an ETP < 400. Considering this threshold, 93% of severe hemophilia patients, 70% of patients with FVIII 1-19% and 52% of patients with FVIII 20-50% had an ETP < 400. Conclusion In severe hemophilia patients, TG was comparable to that in patients with a therapeutic INR. In one-third of non-severe hemophilia patients, TG was higher. These results suggest that anticoagulation therapy should be considered in a substantial proportion of non-severe hemophilia patients.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Case-Control Studies; Cross-Sectional Studies; Drug Monitoring; Female; Hemophilia A; Hemostasis; Humans; International Normalized Ratio; Kinetics; Male; Middle Aged; Phenprocoumon; Severity of Illness Index; Thrombin; Vitamin K; Young Adult

It is unclear whether vitamin K antagonists affect stroke severity and outcome in patients with atrial fibrillation (AF). We aimed to evaluate this association. We prospectively studied 539 consecutive patients admitted with acute ischemic stroke (41.2 % males, age 78.9 ± 6.6 years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). The outcome was assessed with dependency rates at discharge (modified Rankin scale 2-5) and with in-hospital mortality. 177 patients had a history of AF. The median NIHSS at admission did not differ between patients on acenocoumarol with INR 2.0-3.0, on acenocoumarol with INR < 2.0, on single antiplatelet treatment, on dual antiplatelet treatment, or on no treatment [4 (range 0-26), 13 (0-39), 8 (0-33), 3 (2-23) and 7 (0-33), respectively; p = 0.433]. Dependency rates were lower in patients on acenocoumarol with INR 2.0-3.0 or on dual antiplatelet treatment than in those on acenocoumarol with INR < 2.0, single antiplatelet treatment, or no treatment (20.0, 22.2, 61.5, 58.7 and 68.0 %, respectively; p = 0.024). Independent predictors of dependency were age, NIHSS at admission and history of ischemic stroke. In-hospital mortality did not differ between patients on acenocoumarol with INR 2.0-3.0, on acenocoumarol with INR < 2.0, on single antiplatelet treatment, on dual antiplatelet treatment, or on no treatment (7.7, 18.2, 16.1, 16.7 and 22.2 %, respectively; p = 0.822). In conclusion, optimally anticoagulated patients with AF have more favorable functional outcome after stroke and a trend for less severe stroke whereas patients with subtherapeutic anticoagulation have similar stroke severity and outcome with those on no treatment.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Brain Ischemia; Female; Hospital Mortality; Humans; International Normalized Ratio; Male; Platelet Aggregation Inhibitors; Severity of Illness Index; Stroke; Vitamin K

The aim of this study was to compare the efficacy of dabigatran 110 mg twice daily and acenocoumarol in patients with atrial fibrillation discharged after ischemic stroke. We prospectively studied 436 consecutive patients who were discharged after acute ischemic stroke (39.2% males, age 78.6 ± 6.7 years). Approximately 1 year after discharge, the functional status was assessed with the modified Rankin scale (mRS). Adverse outcome was defined as mRS between 2 and 6. The occurrence of ischemic stroke, myocardial infarction (MI) and death during the 1-year follow-up was also recorded. At discharge, 142 patients had atrial fibrillation. Acenocoumarol and dabigatran 110 mg twice daily were prescribed to 52.1 and 6.3% of these patients, respectively. At 1 year after discharge, there was a trend for patients treated with acenocoumarol to have lower mRS than patients prescribed dabigatran (2.3 ± 2.4 and 4.1 ± 2.2, respectively; P = 0.060). Adverse outcome rates and the incidence of stroke during follow-up did not differ between the two groups. The incidence of MI was almost three times higher in patients prescribed dabigatran than in those prescribed acenocoumarol, but this difference did not reach significance (11.1 and 4.0%, respectively; P = 0.254). The incidence of cardiovascular death was also almost three times higher in the former, but again this difference was not significant (33.3 and 12.2%, respectively; P = 0.237). In real-world patients with acute ischemic stroke, dabigatran 110 mg twice daily is as effective as acenocoumarol in preventing stroke but appears to be associated with worse long-term functional outcome and higher incidence of MI.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Brain Ischemia; Dabigatran; Drug Administration Schedule; Female; Humans; Male; Myocardial Infarction; Patient Discharge; Prospective Studies; Stroke; Survival Analysis; Thrombosis

To determine the level of control in treatment compliance in a sample of patients who were treated with acenocoumarol attended in Primary Care settings.. Cross-sectional study. Patients with non-valvular atrial fibrillation treated with acenocoumarol were included. The sample size was calculated based on previous studies. Data of patients who possessed International Normalized Ratio (INR) values in last 6 months in medical consult were collected. It was considered that the INR control was inadequate when the percentage of INR values within the therapeutic range was less than 60% in the last 6 months. Assessment of compliance by telephone interview was conducted by the Morisky-Green Test.. One hundred and ninety-one patients, 110 women (57.6%) with an average age of 76.5±9.4 years were included. Seventy-six patients (39.8%) were in therapeutic range (INR: 2-3) and 115 patients (60.2%) were out of range (below 2 the 20.9% and above 3 the 39.3%). Poor control of INR increased to the age of 85 years (<75 years: 57.8%; 75-85 years: 67.6%;>85 years: 61.5%). Ninety patients responded to the compliance questionnaire (78.3%), being compliant 74 (82.2%) and non-compliant 16 (17.8%).. Six of 10 patients undergoing treatment with acenocoumarol are out of range and nearly 2 of each 10 patients out of range does not accomplish the treatment. We call attention to the need to make a systematically review of adherence in anticoagulated patients attended in Primary Care settings.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cross-Sectional Studies; Drug Monitoring; Female; Humans; International Normalized Ratio; Male; Medication Adherence; Middle Aged; Primary Health Care; Spain

The recently introduced oral direct anticoagulants (ODAs), presumably safer, and with comparable efficacy to the vitamin K antagonists (VKAs), may reshape the world of anticoagulation medicine. This study aimed to assess the prescription appropriateness of ODAs and VKAs at discharge from hospital.. We performed a one year retrospective study between August 2012 and July 2013 in the department of internal medicine of a regional hospital (HVs Sion) using Electronic Medical Records. All patients receiving an ODA were included and matched to a patient treated with a VKA. The appropriateness of prescription at discharge was defined by an adequate indication and dosing, the absence of contraindication, a minimal risk of drug-drug interactions and no major bleeding or venous thromboembolism during the hospitalization. The bleeding risk was evaluated with the HAS-BLED score when the indication was atrial fibrillation (AF).. Out of the 44patients included (22 with an ODA and 22 with a VKA), 38 received an appropriate prescription according to all criteria. Two patients had an inadequate dosing. A potential drug-drug interaction was detected in 3patients receiving a VKA and in 1patient receiving an ODA. No major contraindication was found, but a relative contraindication was discussed in 3cases. The majority of patients receiving an ODA for an AF had a minor bleeding risk.. No significant difference was ascertained between the two groups regarding the appropriateness of prescription. Our results suggest that ODAs were cautiously used in our setting.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Dabigatran; Drug Prescriptions; Female; Humans; Internal Medicine; Male; Middle Aged; Patient Discharge; Phenprocoumon; Retrospective Studies; Rivaroxaban; Vitamin K

Randomized trials showed non-inferior or superior results of the non-vitamin-K-antagonist oral anticoagulants (NOACs) compared with warfarin. The aim of this study was to assess the effectiveness and safety of dabigatran (direct thrombin inhibitor) vs. acenocoumarol (vitamin K antagonist) in patients with atrial fibrillation (AF) in daily clinical practice.. In this observational study, we evaluated all consecutive patients who started anticoagulation because of AF in our outpatient clinic from 2010 to 2013. Data were collected from electronic patient charts. Primary outcomes were stroke or systemic embolism and major bleeding. Propensity score matching was applied to address the non-randomized design. In total, 920 consecutive AF patients were enrolled (442 dabigatran, 478 acenocoumarol), of which 2 × 383 were available for analysis after propensity score matching. Mean follow-up duration was 1.5 ± 0.56 year. The mean calculated stroke risk according to the CHA2DS2-VASc score was 3.5%/year in dabigatran vs. 3.7%/year acenocoumarol-treated patients. The actual incidence rate of stroke or systemic embolism was 0.8%/year [95% confidence interval (CI): 0.2-2.1] vs. 1.0%/year (95% CI: 0.4-2.1), respectively. Multivariable analysis confirmed this lower but non-significant risk in dabigatran vs. acenocoumarol after adjustment for the CHA2DS2-VASc score [hazard ratio (HR)dabigatran = 0.72, 95% CI: 0.20-2.63, P = 0.61]. According to the HAS-BLED score, the mean calculated bleeding risk was 1.7%/year in both groups. Actual incidence rate of major bleeding was 2.1%/year (95% CI: 1.0-3.8) in the dabigatran vs. 4.3%/year (95% CI: 2.9-6.2) in acenocoumarol. This over 50% reduction remained significant after adjustment for the HAS-BLED score (HRdabigatran = 0.45, 95% CI: 0.22-0.93, P = 0.031).. In 'real-world' patients with AF, dabigatran appears to be as effective, but significantly safer than acenocoumarol.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Blood Coagulation; Chi-Square Distribution; Dabigatran; Disease-Free Survival; Drug Monitoring; Electronic Health Records; Female; Hemorrhage; Humans; Incidence; International Normalized Ratio; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Netherlands; Patient Safety; Propensity Score; Proportional Hazards Models; Retrospective Studies; Risk Factors; Stroke; Time Factors; Treatment Outcome

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Polycythemia Vera; Proportional Hazards Models; Risk Factors; Smoking; Thrombophilia; Thrombosis; Warfarin

The use of antithrombotic medication (ATM) frequently is reported in patients with intracranial hemorrhage (ICH) and is associated with increased mortality. Unfortunately, ATMs sometimes are prescribed and/or used inappropriately. We sought to determine the rate of ATM misprescription/misuse among patients with ICH in a single-center retrospective study.. All patients admitted with ATM-related ICH in 1998-2014 were included. Charts were reviewed and demographic, clinical, and radiologic variables were recorded. The type of ATM, dose, and duration of treatment were analyzed critically. The adequacy of ATM prescription/use was assessed in light of the recommendations and guidelines of the American Heart Association, American Stroke Association, and French National Authority for Health, in effect at the time of admission.. A total of 106 patients with mean age 68 years were identified. Aspirin (53.8%) was the most commonly used drug, followed by oral anticoagulants (31.1%) and clopidogrel (22.6%). In only 80 patients (75.5%), the use of ATM was in line with contemporary guidelines. In the remaining 26 (24.5%), the use of ATMs was inappropriate, including bad drug combination, wrong dose, poor indication, wrong drug class, and/or incorrect treatment duration.. In this Lebanese cohort of patients with ICH, the 24.5% rate of ATM misprescription and/or misuse is highly alarming and the origin of this problem is likely multifactorial. Immediate measures should be undertaken, and efforts should be focused on regaining tight control of ATM prescription and fulfillment, ensuring good patient education, and offering more vigilant oversight on physician licensure.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Clopidogrel; Coronary Artery Disease; Enoxaparin; Female; Fibrinolytic Agents; Humans; Inappropriate Prescribing; Intracranial Hemorrhages; Lebanon; Male; Middle Aged; Platelet Aggregation Inhibitors; Prescription Drug Misuse; Retrospective Studies; Risk Factors; Stroke; Ticlopidine; Warfarin; Young Adult

Oral anticoagulants are commonly used to treat patients with thromboembolic pathology. Genetic variations could influence personal response to anticoagulant drugs. Acenocoumarol (AC) is a vitamin K antagonist used in anticoagulant therapy and as a prophylaxis measure in Europe. In this study, we assessed the effect of CYP4F2 rs2108622, ABCB1, and GGCX polymorphisms on the safety profile and regime dosing of AC in patients with nonvalvular atrial fibrillation.. Fifty patients aged 40-70 years were included. All patients received AC in the dose of 1-6 mg daily with a target international normalized ratio of 2.0-3.0. Genotyping for polymorphism markers C3435T for the ABCB1 gene, rs2108622 for the CYP4F2 gene, and rs11676382 for the GGCX gene were designed using polymerase chain reaction and restriction fragment length polymorphism. Statistical analysis was performed using the Fisher exact test and the Mann-Whitney U test.. We found that CYP4F2 rs2108622 CT carriers required a higher AC dose than CC (p=0.0366), and CT and TT carriers required a higher AC dose than CC (p=0.0314).. We found that ABCB1 CT and TT genotypes are associated with a higher risk of bleeding. No influence of ABCB1 and GGCX polymorphisms on the doses of AC was established. CYP4F2 could still be a genetic factor responsible for the personal variability of AC metabolism.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; ATP Binding Cassette Transporter, Subfamily B, Member 1; Atrial Fibrillation; Carbon-Carbon Ligases; Cytochrome P450 Family 4; Dose-Response Relationship, Drug; Female; Hemorrhage; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors; Russia

Mitral stenosis (MS) is frequently associated with the development of atrial fibrillation (AF) as a consequence of hemodynamic and inflammatory changes in the left atrium. Both conditions predispose to thrombus formation, with frequent involvement of the left atrial appendage (LAA), and consequent increase in the incidence of systemic thromboembolic events. Percutaneous mitral valvuloplasty (PMV) reduces the risk of thromboembolism in patients with significant mitral stenosis. Percutaneous LAA closure is also associated with a reduction in thromboembolic risk in patients with AF, but there are no data regarding the use of this technique in patients with significant mitral valve disease. We report the case of a 57-year-old-woman with significant MS and permanent AF, in New York Heart Association functional class II, who despite adequate oral anticoagulation with acenocoumarol, presented several clinical episodes of systemic thromboembolism in the last four years. It was decided to perform a combined percutaneous procedure, including both PMV and percutaneous LAA closure with the Amplatzer Cardiac Plug device. No significant acute complications occurred and the patient was discharged on indefinite treatment with acenocoumarol associated with aspirin 100 mg/d for three months. After a one-year follow-up, there have been no new embolic episodes or other complications.

Topics: Acenocoumarol; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Surgical Procedures; Combined Modality Therapy; Female; Humans; Middle Aged; Mitral Valve Stenosis; Septal Occluder Device; Thromboembolism; Treatment Outcome

Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients.. To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations.. A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR.. Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66-2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations.. BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Longitudinal Studies; Male; Middle Aged; Phenprocoumon; Prognosis; Risk Factors; Venous Thrombosis; Vitamin K

Cost-effectiveness analysis of apixaban (5 mg twice daily) vs acenocoumarol (5mg/day) in the prevention of stroke in patients with nonvalvular atrial fibrillation in Spain.. Markov model covering the patient's entire lifespan with 10 health states. Data on the efficacy and safety of the drugs were provided by the ARISTOTLE trial. Warfarin and acenocoumarol were assumed to have therapeutic equivalence.. The Spanish National Health System and society. Information on the cost of the drugs, complications, and the management of the disease was obtained from Spanish sources.. In a cohort of 1000 patients with nonvalvular atrial fibrillation, administration of apixaban rather than acenocoumarol would avoid 18 strokes, 71 hemorrhages (28 intracranial or major), 2 myocardial infarctions, 1 systemic embolism, and 23 related deaths. Apixaban would prolong life (by 0.187 years) and result in more quality-adjusted life years (by 0.194 years) per patient. With apixaban, the incremental costs for the Spanish National Health System and for society would be € 2,488 and € 1,826 per patient, respectively. Consequently, the costs per life year gained would be € 13,305 and € 9,765 and the costs per quality-adjusted life year gained would be € 12,825 and € 9,412 for the Spanish National Health System and for society, respectively. The stability of the baseline case was confirmed by sensitivity analyses.. According to this analysis, apixaban may be cost-effective in the prevention of stroke in patients with nonvalvular atrial fibrillation compared with acenocoumarol.

Topics: Acenocoumarol; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Drug Costs; Female; Humans; Incidence; Male; Models, Economic; Pyrazoles; Pyridones; Risk Factors; Spain; Stroke

Atrial fibrillation (AF) is a prothrombotic condition, involving increased thrombin generation and fibrinogen concentrations. Vitamin K antagonists (VKAs) prevent arterial thromboembolism if optimal anticoagulation is achieved by individualised drug doses, assessed by determining the Prothrombin time-related International Normalized Ratio (Pt-INR). There is evidence that formation of tight-laced fibrin networks is pathogenic in prothrombotic diseases. This study was performed among AF patients, to test whether long-term treatment with VKAs affects the structure of fibrin networks, and whether the effect is altered by employing different coagulation triggers: exogenous thrombin (1 IU/ml), 10 pM tissue factor (TF) or a commercial Pt-INR reagent (containing 400-fold more TF). In the thrombin-based method, fibrin network porosity (scanning electron microscopy) and liquid permeability (flow measurements) correlated inversely to fibrinogen concentrations, while positive correlations to the degree of anticoagulation were shown with the Pt-INR reagent. In the method with 10 pM TF, the two above relationships were detected, though the influence of Pt-INR was more profound than that of fibrinogen concentrations. Moreover, greater shortening of clot lysis time (CLT) arose from more permeable clots. As a coagulation trigger, 10 pM TF vs exogenous thrombin or the Pt-INR reagent is more informative in reflecting the in vivo process from thrombin generation to fibrin formation. Since fibrin network permeability rose in parallel to elevations of INR and shortening of CLT in AF patients, antithrombotic effects on prevention of thrombotic complications may be achieved from impairment of thrombin generation, resulting in formation of permeable clots susceptible to fibrinolysis.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Case-Control Studies; Fibrin; Fibrin Clot Lysis Time; Humans; International Normalized Ratio; Microscopy, Electron, Scanning; Poland; Porosity; Protein Conformation; Sweden; Thrombin; Thrombosis; Vitamin K; Warfarin

Vitamin K antagonists, despite their tight therapeutic spectrum and the fear of bleeding complications, were long the most important drugs used in anticoagulant therapy. The aim of this study was to evaluate the quality of anticoagulant therapy and its relation with bleedings in everyday clinical practice.. We analyzed the data of 272 patients with non-valvular atrial fibrillation treated in our county hospital using retrospective data collection of the last 1008±384 days. The INR (International Normalized Ratio) values and the time in therapeutic range (TTR) were analyzed. We asked patients about bleeding complications and searched the medical records.. The TTR proved to be 64% and there was no statistically significant difference between that of 252 (92.7%) patients taking acenocoumarol and 20 (7.3%) on warfarin. Analyzing various factors leading to TTR under 70%, we found that none of them have a significant impact. Significantly more bleeding events occurred in the first 3 months after the initiation of anticoagulant therapy and in patients with TTR under 70%, but the latter was not significant after adjustment for factors influencing bleeding (OR 1.607, CI 0.571-4.522, p=0.392).. Although the present study's TTR values were similar to those found in the warfarin branch of various large-scale international trials and in real-life settings, further improvement of vitamin K antagonist therapy are necessary. As the possibilities for this are limited, we believe that the new type anticoagulant agents have a place in everyday clinical practice.

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Hungary; Male; Retrospective Studies; Statistics, Nonparametric; Time Factors; Vitamin K; Warfarin

Aim of the present study was to record the antithrombotic approach in AF and non-AF patients undergoing TAVI, and to compare the efficiency of the used regimens combination. Antithrombotic approach of patients undergoing TAVI remains a challenging dispute. It becomes even more complex when need for anticoagulant treatment is required due to concurrent atrial fibrillation. Consecutive patients with severe symptomatic aortic stenosis treated with TAVI, were retrospectively studied. All patients were divided into two groups, matched to age, depending on the existence of atrial fibrillation. The primary end-point was the composite of MACE, while the secondary end-point was the occurrence of major bleeding at follow-up. A total of 80 patients were included in the study. Out of them, 20 patients (80.2 ± 5.4 years) suffered from concurrent atrial fibrillation. This group was matched with 20 patients (80.6 ± 3.7 years) with no need for anticoagulation. AF-group patients were treated with clopidogrel plus acenocoumarol for 3 months. Following that, acetylsalicylic acid plus acenocoumarol were prescribed. Non-AF patients were treated with 3 months clopidogrel plus acetylsalicylic acid followed by single acetylsalicylic acid medication. No statistical significant differences in MACE between AF and non-AF group were identified (p = 0.705, phi coefficient = 0.06) (mean follow-up 23.4 ± 14 months). Similarly, there was no statistical significant difference for bleedings among the AF and non-AF patient group (p = 0.658, phi coefficient = 0.14). In patients undergoing TAVI with CoreValve, with concurrent AF, treatment with clopidogrel plus acenocoumarol for 3 months, followed by acetylsalicylic acid plus acenocoumarol, seems safe and effective enough in long-term follow-up.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Aortic Valve Stenosis; Atrial Fibrillation; Clopidogrel; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Ticlopidine; Transcatheter Aortic Valve Replacement

Anticoagulation control as assessed by time in therapeutic range (TTR) correlates positively with the safety and efficacy of thromboprophylaxis in atrial fibrillation. We set out to assess TTR in our unit and to investigate determinants of better control.. This was a case series study of atrial fibrillation patients anticoagulated with warfarin or acenocoumarol at the Family Health Unit of Fânzeres. Sociodemographic and clinical data were collected and TTR was calculated by the Rosendaal method, based on international normalized ratio tests performed in external laboratories in the preceding six months. SPSS 21.0 was used for the statistical analysis, with descriptive statistics, Spearman's correlation, and the Mann-Whitney U and Kruskal-Wallis tests.. Of the 106 eligible patients, 70% participated in the study. Median TTR was 65.3% (P25=48.3%, P75=86.8%). We found a positive association between this variable and duration of atrial fibrillation (ρ=0.477, p<0.001, r(2)=0.116) and with duration of anticoagulation (ρ=0.5, p<0.001, r(2)=0.087). No association was found with age, gender, educational level or existence of a caregiver (p>0.05).. Median TTR in our unit is similar to that in southern European countries and close to the good control threshold (70%) proposed by the European Society of Cardiology. The duration of atrial fibrillation and of anticoagulation explains only a small part of the measure's variability. Other determinants of anticoagulation control must be investigated in future studies and comparative studies should be carried out in family health units monitoring anticoagulation on the premises.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Drug Monitoring; Female; Humans; Male; Warfarin

International guidelines recommend that an average individual time in therapeutic range should be >65% to 70% for optimal efficacy and safety outcomes while taking a vitamin K antagonist. The Sex, Age (<60 years); Medical history (at least 2 of the following: hypertension, diabetes, coronary artery disease/myocardial infarction, peripheral arterial disease, congestive heart failure, previous stroke, pulmonary disease, hepatic or renal disease); Treatment (interacting drugs, eg, amiodarone for rhythm control) [all 1 point]; and the current Tobacco use (2 points) and Race (non-Caucasian; 2 points) (SAMe-TT2R2) score would help decision making by identifying those patients with newly diagnosed atrial fibrillation who could do well on vitamin K antagonists. The study objective was to validate the predictive value of the SAMe-TT2R2 score for discriminating those who would achieve a high time in the therapeutic range (≥65%) in a prospective "real-world" cohort of patients with atrial fibrillation initiating oral anticoagulation therapy with vitamin K antagonists.. We studied an inception cohort of consecutive patients with nonvalvular atrial fibrillation who initiated oral anticoagulation in our outpatient anticoagulation clinic. The baseline SAMe-TT2R2 score was calculated. At 6 months, we calculated the time in therapeutic range using a linear method.. We included 459 patients, of whom 222 (47%) were male. Their median age was 76 years (interquartile range, 70-82 years), median Cardiac failure or dysfunction, Hypertension, Age over 75 years [Doubled], Diabetes, Stroke [Doubled] - Vascular disease, Age between 65-74 and Sex category [Female] (CHA2DS2-VASc) score was 4 (3-5), and median Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score was 3 (2-3). The median SAME-TT2R2 score was 2 (1-2). At 6 months, the mean ± standard deviation time in therapeutic range was 64% ± 17% overall, and 248 patients (54%) had a time in therapeutic range value >65%. Patients with a SAME-TT2R2 score 0 to 1 had a mean time in therapeutic range of 67% ± 18%, whereas patients with a SAME-TT2R2 score ≥2 had a mean time in therapeutic range of 61% ± 16% (P < .001). The odds ratio for having a low time in therapeutic range value was 2.10 (95% confidence interval, 1.44-3.06; P < .001) for those patients with a SAME-TT2R2 score ≥2.. In a prospective "real-world" inception cohort of patients with atrial fibrillation initiating oral anticoagulation with acenocoumarol, we have validated the clinical value of the SAME-TT2R2 score for the identification of patients who would have poor-quality anticoagulation. Thus, rather than imposing a "trial of vitamin K antagonists" for such patients (and exposing such patients to thromboembolic risks), we can a priori identify those patients who can (not cannot) do well on a vitamin K antagonists. Such patients would benefit from additional strategies for improving anticoagulation control with vitamin K antagonists or alternative oral anticoagulant drugs.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Clinical Decision-Making; Decision Support Techniques; Female; Health Status Indicators; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Treatment Outcome; Vitamin K

Topics: Acenocoumarol; Administration, Oral; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Drug Monitoring; Drug Substitution; Epistaxis; Factor Xa Inhibitors; Female; Frail Elderly; Humans; Medication Therapy Management; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Renal Insufficiency; Rivaroxaban; Stroke

Time in therapeutic range (TTR) reflects the quality of anticoagulation and is inversely correlated with ischemic stroke in atrial fibrillation (AF) patients. Few data on the relationship between TTR and myocardial infarction (MI) are available. We investigated the association between TTR and Major Adverse Cardiovascular Events (MACE) in a cohort of anticoagulated AF patients.. We calculated TTR for 627 AF patients on vitamin K antagonists, who were followed for a median of 30.8 months (1755 patients/year). The primary outcome was a combined endpoint of MACE including fatal/nonfatal MI and cardiovascular death.. Mean age was 73.3 (±8.2) years, and 40.2% were women. During follow-up, we recorded 67 events: 19 stroke/TIA (1.1%/year) and 48 MACE (2.9%/year): 24 MI and 24 cardiovascular deaths. The cohort was categorized according to tertiles of TTR values: TTR 13-58%, 59-74%, and 75-100%. There was a significant increased rate of MACE across tertiles of TTR (Log-Rank test: p<0.001). On Cox proportion hazard analysis, the 2nd vs. 1st tertile of TTR (p=0.002, hazard ratio [HR] 0.347, confidence interval [CI] 95% 0.177-0.680), 3rd vs. 1st tertile of TTR (p<0.001, HR 0.164, CI 95% 0.067-0.402), age (p<0.001, HR 1.094, CI 95% 1.042-1.148), history of stroke/TIA (p=0.015, HR 2.294, CI 95% 1.172-4.490) and smoking (p=0.003, HR 3.450, CI 95% 1.532-7.769) predicted MACE.. TTR was an independent predictor of MACE in our cohort of AF patients. Our findings suggest that a good anticoagulation control is necessary to reduce not only the risk of stroke but also that of MACE.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Myocardial Infarction; Patient Outcome Assessment; Proportional Hazards Models; Prospective Studies; Regression Analysis; Stroke; Vitamin K; Warfarin

Patients with non-valvular atrial fibrillation who are receiving or have been previously exposed to a vitamin K antagonist could be switched to a non-vitamin K-antagonist oral anticoagulant (NOAC) but little information is available about the risk of bleeding and arterial thromboembolism after such a switch. We aimed to compare the risk of bleeding between individuals who switched and those who remained on a vitamin K antagonist (non-switchers) in real-world conditions.. We did a matched-cohort study with information from French health-care databases. We extracted data for adults (aged ≥18 years) with non-valvular atrial fibrillation who received their first prescription for a vitamin K antagonist (fluindione, warfarin, or acenocoumarol) between Jan 1, 2011, and Nov 30, 2012, and who were either switched to a NOAC (dabigatran or rivaroxaban) or maintained on the vitamin K antagonist. Each switcher was matched with up to two non-switchers on the basis of eight variables, including sex, age, and international normalised ratio number. The primary endpoint was incidence of bleeding (intracranial haemorrhage, gastrointestinal haemorrhage, or other) in switchers versus non-switchers, and switchers stratified by type of NOAC versus non-switchers, noted from databases of hospital admissions. Each patient was followed up to 1 year; the study closed on Oct 1, 2013.. Of 17,410 participants, 6705 switched to a NOAC (switchers) and 10,705 remained on vitamin K-antagonist therapy (non-switchers). Median age of participants was 75 years (IQR 67-82), 8339 (48%) were women, and the median duration of vitamin K-antagonist exposure before a switch was 8.1 months (IQR 3.9-14.0). After a median follow-up of 10.0 months (IQR 9.8-10.0), we noted no difference between groups for bleeding events (99 [1%] in switchers vs 193 [2%] in non-switchers, p=0.54). In adjusted multivariate analyses, the risk of bleeding in switchers was not different from that in non-switchers (hazard ratio [HR] 0.87; 95% CI 0.67-1.13, p=0.30). Additionally, no differences were noted when the risk of bleeding was compared between switchers from a vitamin K antagonist to dabigatran (HR 0.78, 95% CI 0.54-1.09, p=0.15), switchers from a vitamin K antagonist to rivaroxaban (HR 1.04, 95% CI 0.68-1.58, p=0.86), and non-switchers.. In this matched-cohort study, our findings suggest that patients with non-valvular atrial fibrillation who switch their oral anticoagulant treatment from a vitamin K antagonist to a non-vitamin K antagonist are not at increased risk of bleeding. Future studies with longer follow-up might be needed.. None.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Hemorrhage; Humans; Male; Phenindione; Retrospective Studies; Risk Factors; Rivaroxaban; Stroke; Thromboembolism; Vitamin K; Warfarin

Due to improved implementation of guidelines, new scoring approaches to improve risk categorisation, and introduction of novel oral anticoagulants, medical management of patients with atrial fibrillation (AF) is continuously improving. The PREFER in AF registry enrolled 7,243 consecutive patients with ECG-confirmed AF in seven European countries in 2012-2013 (mean age: 71.5 ± 10.7 years; 60.1% males; mean CHA2DS2-VASc score: 3.4). While patient characteristics were generally homogeneous across countries, anticoagulation management showed important differences: the proportion of patients taking vitamin K antagonists (VKAs) varied between 86.0% (in France) and 71.4% (in Italy). Warfarin was used predominantly in the UK and Italy (74.9% and 62.0%, respectively), phenprocoumon in Germany (74.1%), acenocoumarol in Spain (67.3%), and fluindione in France (61.8 %). The major sites for international normalised ratio (INR) measurements were biology laboratories in France, anticoagulation clinics in Italy, Spain, and the UK, and physicians' offices or self-measurement in Germany. Temporary VKA discontinuation and bridging with other anticoagulants was frequent (at least once in the previous 12 months for 22.9% of the patients, on average; ranging from 29.7% in Germany to 14.9% in the UK). Time in therapeutic range (TTR), defined as at least two of the last three available INR values between 2.0-3.0 prior to enrolment, ranged from 70.3% in Spain to 81.4% in Germany. TTR was constantly overestimated by physicians. While the type and half-lives of VKA as well as the mode of INR surveillance differed, overall quality of anticoagulation management by TTR was relatively homogenous in AF patients across countries.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Europe; Female; Humans; Male; Middle Aged; Phenindione; Phenprocoumon; Practice Guidelines as Topic; Registries; Vitamin K; Warfarin; Withholding Treatment

Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Stroke

Long-term anticoagulation therapy using vitamin K antagonists (VKA) is used in millions of patients worldwide to reduce the risk of thrombotic or thromboembolic events. Control and monitoring of VKA therapy is improved by the regular self-measurement of international normalized ratio (INR) using a home monitoring device. This retrospective analysis of a large cohort of patients in the Netherlands seeks to determine whether the choice of INR monitor could have a clinical impact on patient outcomes.. The National Thrombosis Service provides medical supervision, training and support to anticoagulant patients eligible for home-monitoring of INR in the Netherlands. Two INR monitors (CoaguChek XS and INRatio2) have been distributed at random to patients since June 2011, and patient self-testing data (INR measurements and other clinical parameters) have been recorded to measure and improve treatment outcomes. The data have been retrospectively analyzed to determine any effect of the choice of monitor. Univariate and multivariate statistical tests are used to assess any differences between groups in terms of efficacy and safety parameters.. Data from 4,326 patients were collated, and 156,507 INR values were included in the analysis. Over half the patients (54.3%) were being treated for atrial fibrillation, and 77.6% were prescribed acenocoumarol. There were few differences between the patient populations using the two different monitors. Anticoagulant control overall was good, with high percentage of time (87.9%) in the appropriate INR range and low incidence of excessively high or low INR values (0.085/month). Minor clinical events related to safety were low (0.78 per patient-year) and showed few differences between monitors. Mortality rates were similar [hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.65-1.70].. Self-testing data from a large cohort of patients in the Netherlands suggest that there is no clinically relevant effect of the choice of coagulation monitor (CoaguChek XS or INRatio2) on the time in therapeutic range (TTR), minor or fatal outcomes of long-term anticoagulation management.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Diagnostic Equipment; Disease Management; Drug Monitoring; Female; Humans; International Normalized Ratio; Male; Middle Aged; Netherlands; Point-of-Care Testing; Retrospective Studies; Treatment Outcome

Vitamin K antagonists (VKAs) remain as the most prescribed drug for treatment and prevention of thrombotic disorders in many countries, despite the recent approval of the new oral anticoagulants (NOACs). Although effectiveness and safety of VKAs are tightly associated to maintaining the patient within the international normalised ratio (INR) therapeutic range (TWR), they have been likened to NOACs when patients are in good INR control (≥66% of TWR). Therefore, assessing the safety of patients should be a priority in the selection of the anticoagulation therapy. The aim of this study was to evaluate the association between CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2*3, ABCB1 C3435T, APOE, CYP2C19*2 and CYP2C19*17 gene polymorphisms and treatment safety in 128 patients diagnosed with atrial fibrillation or venous thromboembolism during the initial first seven months of acenocoumarol therapy. After the first month, VKORC1-T-allele and APOE-E3/E3 genotype were independently associated to higher time above therapeutic range (TAR) and lower time below the therapeutic range (TBR). After seven months, VKORC1 T-allele predicted higher TAR, and was also associated to increased INR>4, particularly the TT-genotype (odds ratio [OR]: 32; 95% confidence interval [CI95%]: 6-175; p=810⁻⁵). C-alleles for CYP2C9*3 (OR: 5.5; CI95%: 1.8-17; p=0.003) and ABCB1 (OR: 8.9;CI95%: 1.1-70; p=0.039) independently influenced on INR>6 . Patients VKORC1-TT/ABCB1-C remained 26.8% [19.7-38.9] TAR, with associated relative risk (RR) for INR>4 1.8 higher (CI95%: 1.2-2.5; p=0.015). Patients VKORC1-TT also presented the highest risk of bleeding events (RR: 3.5;CI95%: 1.4-8.4; p=0,010). In conclusion, VKORC1, CYP2C9*3, APOE and ABCB1 genotypes should be considered in prevention of overanticoagulation and bleeding events in the initiation of acenocoumarol therapy.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Alleles; Anticoagulants; Apolipoproteins E; ATP Binding Cassette Transporter, Subfamily B; Atrial Fibrillation; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Female; Follow-Up Studies; Genetic Association Studies; Genotype; Hemorrhage; Humans; Male; Middle Aged; Pharmacogenetics; Polymorphism, Genetic; Venous Thromboembolism; Vitamin K Epoxide Reductases

Drug interactions can cause many clinical problems, particularly when the drugs are administered in combination with anticancer agents.. A patient required two hospitalizations due to risk of bleeding with altered INR probably due to an interaction between gefitinib and acenocoumarol, which resulted in the potentiation of the effect of the latter and acenocoumarol dose adjustment was needed. A causality assessment between the drug-drug interaction and the augmented INR was conducted according to Naranjo algorithm and was classified as a definite adverse drug reaction.. Patient's management recommended is to closely monitor for changes in the effects of coumarin derivatives, if administered concomitantly with antineoplasic agents.

Topics: Acenocoumarol; Adenocarcinoma; Aged; Anticoagulants; Antineoplastic Agents; Atrial Fibrillation; Carcinoma, Non-Small-Cell Lung; Drug Interactions; Gefitinib; Heart Failure; Humans; International Normalized Ratio; Lung Neoplasms; Male; Protein Kinase Inhibitors; Quinazolines

To develop an acenocoumarol (ACN) dosing algorithm for patients with atrial fibrillation or venous thromboembolism, considering the influence on the stable ACN dose of clinical factors and gene polymorphisms, including CYP2C9*2/*3, VKORC1, CYP4F2*3, ABCB1, APOE, CYP2C19*2/*17, and GGCX.. A retrospective observational study was carried out to obtain clinical and pharmacogenetic dose algorithms by multiple linear regression of results in a cohort of 134 patients under treatment with a stable ACN dose for atrial fibrillation or venous thromboembolism and to test them in an independent validation cohort of 30 patients.The pharmacogenetic dosing algorithm included CYP2C9, VKORC1, and APOE, which explained 56.6% of the variability in the stable ACN dose. Lower deviation from the stable dose and increased accuracy were shown by the pharmacogenetic algorithm, which correctly classified 67% of patients with a deviation of up to 20%.. The variability in the stable ACN dose was better explained by a pharmacogenetic algorithm including clinical and genetic factors (CYP2C9, VKORC1, and APOE) than by a clinical algorithm, providing a more accurate dosage prediction.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Apolipoproteins E; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Drug Dosage Calculations; Female; Genetic Variation; Humans; Male; Middle Aged; Pharmacogenetics; Retrospective Studies; Venous Thromboembolism; Vitamin K Epoxide Reductases

Chronic Kidney Disease (CKD) constitutes an adverse risk factor in chronic anticoagulated atrial fibrillation (AF) patients, being related to adverse cardiovascular events, mortality and major bleeds. It is unclear if CKD adds independent prognostic information to stroke risk stratification schemes, as the risk factor components of the CHADS2 and CHA2DS2-VASc scores are themselves related to renal dysfunction. The aim of our study was to determine if CKD independently improves the predictive value of the CHADS2 and CHA2DS2-VASc stroke stratification scores in AF. We recruited consecutive patients (n=978) patients (49% male; median age 76) with permanent or paroxysmal AF on oral anticoagulants with acenocoumarol, from our out-patient anticoagulation clinic. After a median follow-up of 875 (IQR 706-1059) days, we recorded stroke/transient ischaemic attack (TIA), peripheral embolism, vascular events (acute coronary syndrome, acute heart failure and cardiac death) and all-cause mortality. During follow-up, 113 patients (4.82%/year) experienced an adverse cardiovascular event, of which 39 (1.66%/year) were strokes, 43 (1.83%/year) had an acute coronary syndrome and 32 (1.37%/year) had acute heart failure. Also, 102 patients (4.35%/year) died during the following up, 31 of them (1.32%/year) as a result of a thrombotic event. Based on c-statistics and the integrated discrimination improvement (IDI), CKD did not improve the prediction for stroke/systemic embolism, thrombotic events and all-cause mortality using the CHADS2 and CHA2DS2-VASc scores. In conclusion, evaluating renal function in AF patients is important as CKD would confer a poor overall prognosis in terms of thromboembolic events and all-cause mortality. Adding CKD to the CHADS2 and CHA2DS2-VASc stroke risk scores did not independently add predictive information.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Atrial Fibrillation; Decision Support Techniques; Female; Humans; Ischemic Attack, Transient; Kidney; Male; Multivariate Analysis; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome

Hypertension is the most frequent condition associated with atrial fibrillation (AF) and stroke, the most terrible complication of AF. Achieving blood pressure (BP) goals as well as an adequate antithrombotic treatment are critical to reduce the incidence of stroke. But are interactions between anticoagulants and antihypertensive agents relevant for achieving BP targets? We present the case of a patient with hypertension and AF in which the interaction between losartan and acenocoumarol was associated with an irregular systolic BP control, but after switching to dabigatran, BP control improved. In this report, the possible mechanisms that may explain this change are discussed.

Topics: Acenocoumarol; Aged, 80 and over; Anticoagulants; Antihypertensive Agents; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Interactions; Humans; Hypertension; Losartan; Male

To develop and validate an algorithm for the prediction of therapeutic dose of acenocoumarol in Romanian patients.. The inclusion criteria for entry to the study was age ≥ 18 years and starting acenocoumarol treatment for at least one of the following clinical indications: acute deep vein thrombosis of the lower limbs, persistent or permanent atrial fibrillation, and/or the presence of valvular prostheses requiring prolonged oral anticoagulant therapy. The patients were followed up for 3 months. Patients admitted to the internal medicine, cardiology, and geriatrics wards of the Municipal Clinical Hospital, Cluj-Napoca and "Niculae Stăncioiu" Heart Institute between October 2009 and June 2011 who fulfilled the inclusion criteria were included in the study. Clinical and demographic data that could influence the acenocoumarol stable dose were recorded for each patient. Genetic analysis included the genotyping the CYP2C9*2 and *3, and the VKORC1 -1693 G > A polymorphisms. The patients were randomly divided into two groups: (1) the main group on which the development of the clinical and genetic algorithms for acenocoumarol dose prediction was based; (2) the validation group.. The study included 301 patients, of whom 155 were women (51.5 %) and 146 were men (48.5 %). The median age of the patient cohort was 66 (women, 57; men, 73) years. After randomization the main group comprised 200 patients (66.4 %) and the validation group 101 patients (33.6 %). Age and body mass index explained 18.8 % (R (2)) of the variability in acenocoumarol weekly dose in patients in the main group. When the genetic data were added to the algorithm, the CYP2C9*2 and *3 polymorphisms and the VKORC1 -1693 G > A polymorphism accounted for 4.7 and 19. 6 % of acenocoumarol dose variability, respectively. For the main group, we calculated a mean absolute error of 5 mg/week (0.71 mg/day). In the validation group, clinical parameters explained 22.2 % of the weekly acenocoumarol dose variability. Genetic polymorphisms increased the R(2) coefficient to 32.8 %.. We have developed and validated an accurate algorithm for prediction of the stable therapeutic dose of acenocoumarol in a Romania population.

Topics: Acenocoumarol; Aged; Algorithms; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Polymorphism, Genetic; Romania; Venous Thrombosis; Vitamin K Epoxide Reductases; White People

Although traditionally observed in patients with end-stage renal disease and secondary hyperparathyroidism, calciphylaxis has been reported in patients with normal renal and parathyroid function. There is no evidence-based therapy available. The use of sodium thiosulfate (STS) has been increasingly described. Herein we describe two patients who responded well to this treatment.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Atrial Fibrillation; Calciphylaxis; Comorbidity; Diabetes Mellitus, Type 2; Drug Substitution; Female; Heparin, Low-Molecular-Weight; Humans; Hyperparathyroidism, Secondary; Livedo Reticularis; Obesity; Peripheral Vascular Diseases; Risk Factors; Shock, Septic; Thiosulfates; Urinary Tract Infections; Vitamin D Deficiency

The aim of this study was to test the hypothesis that a specific bleeding risk score, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), was better at predicting major bleeding compared with CHADS2 (congestive heart failure, hypertension, 75 years of age or older, diabetes mellitus, and previous stroke or transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, 75 years of age and older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, 65 to 74 years of age, female) in anticoagulated atrial fibrillation (AF) patients.. The CHADS2 and CHA2DS2-VASc scores are well-validated stroke risk prediction scores for AF, but are also associated with increased bleeding and mortality.. We recruited 1,370 consecutive AF patients (49% male; median age, 76 years) receiving oral anticoagulation therapy from our outpatient anticoagulation clinic, all of whom were receiving acenocoumarol and had an international normalized ratio between 2.0 and 3.0 during the preceding 6 months. During follow-up, major bleeding events were identified by the 2005 International Society on Thrombosis and Haemostasis criteria. Model performance was evaluated by calculating the C-statistic, and the improvement in predictive accuracy was evaluated by calculating the net reclassification improvement and integrated discrimination improvement.. After a median follow-up of 996 (range, 802 to 1,254) days, 114 patients (3.0%/year) presented with a major bleeding event; 31 of these events were intracranial hemorrhages (0.8%/year). Based on the C-statistic, HAS-BLED had a model performance superior to that of both CHADS2 and CHA2DS2-VASc (both p < 0.001). Both net reclassification improvement and integrated discrimination improvement analyses also show that HAS-BLED was more accurately associated with major bleeding compared with CHADS2 and CHA2DS2-VASc scores.. In anticoagulated AF patients, a validated specific bleeding risk score, HAS-BLED, should be used for assessing major bleeding. The practice of using CHADS2 and CHA2DS2-VASc as a measure of high bleeding risk should be discouraged, given its inferior predictive performance compared with the HAS-BLED score.

Topics: Acenocoumarol; Adult; Age Factors; Aged; Alcohol Drinking; Anticoagulants; Atrial Fibrillation; Diabetes Complications; Female; Follow-Up Studies; Heart Failure; Hemorrhage; Humans; Hypertension; International Normalized Ratio; Ischemic Attack, Transient; Kidney; Liver; Male; Middle Aged; Predictive Value of Tests; Risk Assessment; Risk Factors; Stroke; Substance-Related Disorders

Despite the recent emergence of new oral anticoagulants, vitamin K antagonists remain the primary therapy in patients with atrial fibrillation and the only therapy licensed for use in patients with artificial heart valves.. The aim of this study was (a) to assess the impact of clinical and genetic factors on acenocoumarol (AC) dose requirements and the percentage of time in therapeutic range (%TTR) and (b) to develop pharmacogenetic-guided AC dose calculation algorithm.. We included 235 outpatients of the Institute of Cardiology (Warsaw), mean age 69.3, 46.9% women, receiving AC for artificial heart valves and/or atrial fibrillation. A multiple linear-regression analysis was performed using log-transformed effective AC dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other clinical factors as independent predictors.. We identified factors that influenced the AC dose: CYP2C9 polymorphisms (P=0.004), VKORC1 polymorphisms (P<0.0001), age (P<0.0001), creatinine clearance lower than 40 ml/min (P=0.035), body mass (P=0.02), and dietary vitamin K intake (P=0.026). Clinical and genetic factors explained 49.0% of AC dose variability. We developed a dosing calculation algorithm that is, to the best of our knowledge, the first one to assess the effect of such clinical factors as creatinine clearance and dietary vitamin K intake on the AC dose. The clinical usefulness of the algorithm was assessed on separate validation group (n=50) with 70% accuracy. Dietary vitamin K intake higher than 200 mcg/day improved international normalized ratio control (%TTR 73.3±17 vs. 67.7±18, respectively, P=0.04).. Inclusion of a variety of genetic and clinical factors in the dosing calculation algorithm allows for precise AC dose estimation in most patients and thus improves the efficacy and safety of the therapy.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Algorithms; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Body Mass Index; Creatinine; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Genetic Markers; Genetic Variation; Genotype; Heart Valve Prosthesis; Humans; Linear Models; Male; Middle Aged; Poland; Polymorphism, Single Nucleotide; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases

Topics: Acenocoumarol; Aged, 80 and over; Anticoagulants; Asthma; Atrial Fibrillation; Calciphylaxis; Calcium; Diabetes Complications; Female; Humans; Hypertension; Leg Ulcer; Livedo Reticularis; Polypharmacy; Thrombophilia

Atrial fibrillation is a risk factor for ischemic stroke. To prevent stroke oral anticoagulants can be administered. Old and new types of anticoagulants are available. Nowadays, old type, acenocumarol based anticoagulants are used preferentially in Hungary.. The advantages and the disadvantages of anticoagulants are well known, but anticoagulants are underused in many cases.. The authors retrospectively examined how frequent atrial fibrillation was and whether the usage of anticoagulants in practice was in accordance with current guidelines among acute stroke cases admitted to the Department of Neurology, Medical and Health Science Centre of Debrecen University in 2009.. Of the 461 acute stroke cases, 96 patients had known and 22 patients had newly discovered atrial fibrillation. Half of the patients did not receive proper anticoagulation. Only 8.4% of them had their INR levels within the therapeutic range.. The findings are similar to those reported in other studies. Many factors may contribute to the high proportion of improper use of anticoagulants, and further investigations are needed to determine these factors. In any case, elimination of these factors leading to a failure of anticoagulation may decrease the incidence of stroke.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Drug Prescriptions; Female; Hemorrhage; Humans; Hungary; Incidence; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Risk Factors; Stroke; Treatment Outcome

A drug interaction between capecitabine and coumarin may result in an increased INR and bleeding complications.. We describe an 80-year-old woman who presented with rectal bleeding and an increased INR due to the concomitant use of acenocoumarol and capecitabine for atrial fibrillation and metastatic cecal cancer, respectively.. In patients with a compelling indication for treatment with capecitabine and anticoagulant therapy, conversion to low-molecular weight heparin should be considered.

Topics: Acenocoumarol; Aged, 80 and over; Anticoagulants; Antimetabolites, Antineoplastic; Atrial Fibrillation; Capecitabine; Deoxycytidine; Drug Interactions; Erythrocyte Transfusion; Female; Fluorouracil; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Rectal Neoplasms

The study included 52 patients at a high risk of thromboembolic complications, with permanent atrial fibrillation. All patients were treated with acenocoumarol for 6 months and the incidence of hemorrhages was evaluated in all of them. All patients were genotyped by CYP2C9 and VKORC1. The presence of CYP2C9*2 and CYP2C9*3 alleles of CYP2C9 locus and AA genotype of VCORC1 gene polymorphic G-1639(3673)A marker was not associated with the development of hemorrhages under conditions of acenocoumarol treatment (p=0.144 for CYP2C9, p=0.809 and 0.918 for VCORC1 in the total group and subgroup of patients with CYP2C9*1/*1 genotype, respectively). The search for other genetic markers of acenocoumarol efficiency and safety is needed for predicting the risk of hemorrhages during this treatment.

Topics: Acenocoumarol; Alleles; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Cytochrome P-450 CYP2C9; Genetic Loci; Genotype; Genotyping Techniques; Hemorrhage; Humans; International Normalized Ratio; Mixed Function Oxygenases; Polymorphism, Genetic; Retrospective Studies; Risk; Russia; Thromboembolism; Vitamin K Epoxide Reductases

For the last 60 years, heparin and vitamin K antagonists have been the cornerstone of anticoagulation. Nowadays, the new anticoagulants, such as dabigatran, rivaroxaban and apixaban, show potential advantages over classical treatments. These agents inhibit specific coagulation factors and are administered orally at fixed doses. Furthermore, heparin and vitamin K antagonists have a fast onset of action, short-duration and predictable therapeutic effects. No interactions with foods have been described, although some drug-drug interactions have been reported. At the moment, no antidotes are available. However, due to the short half-life of these agents, antidotes are less essential. The new anticoagulants are at least as effective and safe as traditional treatments in the prevention of venous thromboembolism after orthopedic surgery, as well as in the prevention of stroke and systemic embolism in non-valvular atrial fibrillation. Dabigatran and rivaroxaban have also been shown to be effective in the treatment of acute venous thromboembolism. Due to their properties, these drugs could gradually replace heparin and especially vitamin K antagonists. Hopefully, many of our patients will be able to discontinue classical anticoagulant treatment and others will never begin it.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Heparin; Humans; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Treatment Outcome; Venous Thromboembolism; Warfarin

To evaluate differences in the treatment quality between often used oral anticoagulants, warfarin and acenocoumarol in patients with nonvalvular atrial fibrillation (NVAF).. This was an observational, comparative, one-year clinical study, conducted in the Blood Transfusion Institute of Sarajevo, Bosnia & Herzegovina. All patients who were using warfarin/ acenocoumarol and monitored were eligible. Patients who met inclusion criteria (the age of 40-80, diagnosed NVAF, CHADS index score > or = 2, the planned long-term treatment) were includes in two parallel groups of 60 patients, composed according to the warfarin/acenocoumarol treatment as well as the gender and age. Routinely measured International normalised ratio (INR) values were the basic parameter for individual quality and stability assessment.. All average, monthly INR values were in therapeutic range (2.0-3.0) in both therapeutic groups. There were no significant differences either in the number of therapeutic INR values per patient (50.53 +/- 23.72% vs. 51.74 +/- 26.68%, P = 0.795) or in individual quality of treatment: > 50% therapeutic INR values (60.0% vs. 64.9%, P = 0.721) and > 75% therapeutic INR values (18.3% vs. 22.8%, P = 0.714) in the warfarin and acenocoumarol group, respectively. Significantly better stability was determined for acenocoumarol as compared with warfarin treatment in terms of a longer period of the total observed time during which therapeutic INR values were stable (37.6% vs. 35.7%, P = 0.0002).. Both drugs have shown similar quality of individual anticoagulation control, but acenocoumarol have shown significantly better anticoagulation stability with therapeutic INR values covering significantly longer time of treatment.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Female; Humans; International Normalized Ratio; Male; Warfarin

Patients with atrial fibrillation (AF) at risk of stroke are not always anticoagulated with vitamin K antagonists (VKA) despite lack of contraindication. Dabigatran, an oral direct thrombin inhibitor, is a new option with proven safety and effectiveness in these patients. The advantages of dabigatran are its more predictable response, obviating coagulation monitoring and possible lower frequency of bleedings. Its drawbacks are cost, lack of antidote and long-term data, frequency of dyspepsia and the twice daily dosage.

Topics: Acenocoumarol; Aged, 80 and over; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Female; Humans; Risk Assessment; Stroke; Vitamin K

The study included 25 patients at high risk of thromboembolic complications. All of them were treated with acenocoumarol for 6 months under control of the frequency of hemorrhage and episodes of severe hypocoagulation (a more than 3-fold rise in INR). All the patients underwent CYP2C9 and VKORC1 genotyping. It was shown that the presence of CYP2C9*2 and CYP2C9*3 alleles in the CYP2C9 locus and the AA genotype of the polymorphous G-1639(3673)A marker of the VKORC1 gene was not associated with the development of severe hypocoagulation episodes (p = 0.261--for CYP2C9, p = 0.616 and 0.361 for VKORC1 in the total group and a subgroup of patients having the CYP2C9*1/*1 genotype respectively and treated with acenocoumarol. The search for other genetic markers of efficacy and safety of this drug should be continued.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Cohort Studies; Cytochrome P-450 CYP2C9; Female; Humans; Male; Middle Aged; Mixed Function Oxygenases; Polymorphism, Genetic; Russia; Thromboembolism; Vitamin K Epoxide Reductases

International normalized ratio (INR) is used to monitor chronic oral anticoagulant (OA) treatment; however, it is poorly understood how this simple test reflects in vivo hemostatic reactions, culminating in thrombin generation and clot formation. We studied the process of thrombin generation using an ex vivo model, where thrombin-antithrombin (TAT) complexes are measured in blood emerging from standardized skin incisions in 55 patients (35 with venous thromboembolism [VTE] and 20 with sustained atrial fibrillation [AF]) treated with acenocoumarol (INR 2.0-3.0). In addition, in venous blood, we measured the activity of factor VIII (FVIII) and vitamin K-dependent coagulation proteins. Chronic anticoagulation led to significant reductions in maximum TAT concentrations as compared to 35 healthy controls, in maximum TAT generation rates, and in mean amount of thrombin generated. Parameters of thrombin generation did not correlate with INR or any coagulation factor measured. International normalized ratio was significantly and independently affected by the decrease in the activity of all vitamin K-dependent coagulation proteins. The strongest influence was shown for FVII. Factor VIII activity was increased in all patients studied independently of the duration of anticoagulation and did not change over time. In conclusion, in patients with VTE and AF on OA, there is no correlation between INR values and parameters of ex vivo thrombin generation. This may indicate an important role of protein C (PC) system and possibly other endothelium-dependent mechanisms in controlling hemostasis. Increased FVIII activity in patients with VTE and AF does not change significantly during anticoagulation and is probably related to the pretreatment prothrombotic state.

Topics: Acenocoumarol; Anticoagulants; Antithrombins; Atrial Fibrillation; Case-Control Studies; Factor VIII; Female; Humans; International Normalized Ratio; Long-Term Care; Male; Middle Aged; Prothrombin; Thrombin; Venous Thromboembolism

A daily dose of vitamin K antagonists (VKAs) may vary and its range depends on various interrelated factors. Low responsiveness to VKA (defined as a failure to achieve a target international normalized ratio [INR]) is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex gene (VKORC1). A highly prevalent promoter single-nucleotide polymorphism (VKORC1-1639 G>A, rs17878363) impairs VKORC1 expression and determines the interindividual variability of the target INR. We studied 57 patients receiving oral anticoagulation, including 50 subjects treated with acenocoumarol (mean dose: 5.7+/-2.3 mg/day) and 7 treated with warfarin (mean dose: 9.6+/-4.2 mg/day). The indications for the use of oral anticoagulant therapy were as follows: deep-vein thrombosis (N = 23); pulmonary embolism (N = 20); arterial thrombosis (N = 5); stroke (N = 4); atrial fibrillation with transient ischemic attacks (N = 2), and history of multiple thromboembolic events (N = 3). Identification of the VKORC1 genomic variation was performed using DNA sequencing methods. The prevalence of the mutated allele (VKORC1 -1639A) was 41%. The VKORC1 -1639G allele carriers required a higher daily dose of acenocoumarol (5.9+/-1.9 mg) than the noncarriers (4.1+/-3.3 mg; P < 0.001). All of 5 low responders (who failed to achieve a target INR using standard dose requirements of VKAs) were homozygous for the 1639G allele. Low responders did not differ from good responders with respect to age, gender, and body mass index. Our findings suggest the potential benefits from pharmacogenetic testing, and provide evidence that the VKORC1 -1639 G>A gene polymorphism may explain at least in part the low responsiveness to acenocoumarol.

Topics: Acenocoumarol; Adult; Alleles; Anticoagulants; Atrial Fibrillation; Base Sequence; DNA Primers; Dose-Response Relationship, Drug; Drug Resistance; Female; Gene Frequency; Humans; International Normalized Ratio; Male; Middle Aged; Mixed Function Oxygenases; Poland; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Pulmonary Embolism; Venous Thrombosis; Vitamin K; Vitamin K Epoxide Reductases; Warfarin

Long half life oral anticoagulants have shown a higher anticoagulation stability and a lower hemorragic risk than those of a short half life. We have compared therapeutic stability and hemorragic risk of acenocoumarol versus warfarin in 2 groups of patients on preventive anticoagulation because of atrial fibrilation (international normalised ratio [INR]: 2-3).. Data on 120 patients treated with acenocoumarol and 120 on warfarin treatment who had started and continued treatment in our hospital for a minimum of a year was collected.. The percentage of visits within the intended range of INR (2 to 3) was 65.5% with warfarin and 63.4% with acenocoumarol. Thirty percent of patients on warfarin had 75% or more of their controls within range, while for those treated with acenocoumarol this percentage was 22.5%. In the acenocoumarol group, 0.3 visits/patient/year presented an INR > or = 6 versus 0.07 in the warfarin group (p = 0.003).. Patients treated with acenocoumarol show a higher risk of presenting with an INR > or = 6, but no statistically significant differences are observed in therapeutic stability.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Retrospective Studies; Risk Factors; Warfarin

A 62-year-old woman was referred to the dermatology department for a history of fever, asthenia and cutaneous rash, which appeared after a 3-day course of digitalin and acenocoumarol for atrial fibrillation. The physical examination revealed multiple round confluent purpuric lesions over her entire legs with no blistering. Laboratory exams were all negative. Biopsy of the involved skin was compatible with leucocytoclastic vasculitis. The acenocoumarol treatment was withheld and the skin lesions resolved spontaneously over the next 10 days. The cause of this purpura was seemingly acenocoumarol because of the close temporal relationship between exposure to the drug and the onset of the symptoms, and the spontaneous resolution of the lesions after acenocoumarol was discontinued. This observation illustrates a rare association between vasculitis and acenocoumarol. Clinicians should be aware of this potential adverse effect and recommend interrupting the drug intake when temporal relation is evocative.

Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Diagnosis, Differential; Drug Eruptions; Female; Humans; Leg Dermatoses; Middle Aged; Vasculitis, Leukocytoclastic, Cutaneous

Expert oral anticoagulation management is the key to good outcomes and is performed variably in different health care systems throughout the world. We set out to assess the quality of anticoagulation management in five countries in patients receiving vitamin K antagonists (VKAs) for stroke prophylaxis in chronic non-valvular atrial fibrillation (NVAF), and to compare the anticoagulation management practices in these countries.. This was a retrospective, multi-centre cohort study in the United States, Canada, France, Italy, and Spain. About 1,511 patients were randomly recruited from representative practices (routine medical care (RMC) in the US, Canada, and France; anticoagulation clinics in Italy and Spain) and data pertaining to their oral anticoagulation care were abstracted from their medical records. The predominant anticoagulant in use was warfarin in the US, Canada, and Italy; acenocoumarol in Spain; and fluindione in France. Documentation of care was poor in the US, Canada, and France, countries where RMC was studied. Percent INRs or time-in-therapeutic range was greater in the two anticoagulation clinic samples compared with the RMC samples.. Oral anticoagulation care varies considerably from country to country. Findings suggest that anticoagulation clinic care (ACC) may provide better outcomes as assessed by international normalized ratio (INR) time-in-range. Physicians tend to under treat more than over treat. Finally, documentation of care is often inadequate. Condensed Abstract Oral anticoagulation management (routine medical care or anticoagulation clinic care) was retrospectively assessed in 5 countries using a uniform, structured assessment tool. Major management differences were detected, especially between anticoagulation clinic care and routine care. Documentation was often a problem in the latter setting. Less time in therapeutic INR range was noted in routine medical care. Findings suggest that anticoagulation clinic care may provide better outcomes as assessed by international normalized ratio (INR) time-in-range. Physicians tend to under treat more than over treat. Finally, documentation of care is often inadequate.

Topics: Acenocoumarol; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Canada; Cohort Studies; Drug Monitoring; Female; France; Humans; International Normalized Ratio; Italy; Male; Middle Aged; Phenindione; Practice Patterns, Physicians'; Quality of Health Care; Retrospective Studies; Spain; Stroke; Treatment Outcome; United States; Warfarin

We present a case of a 58-year-old male being treated for dilated cardiomyopathy and atrial fibrillation for more than ten years who was admitted to the intensive care unit with the diagnosis of acute ST-segment elevation myocardial infarction (STEMI). In course of further diagnostics the coronary artery embolism resulting from the unintentional anticoagulant drug (acenocumarol) dose reduction was established as the most probable cause of STEMI. Primary percutaneous coronary intervention was successfully performed and the patient was discharged home in good clinical condition.

Topics: Acenocoumarol; Angioplasty, Balloon, Coronary; Anticoagulants; Atrial Fibrillation; Cardiomyopathy, Dilated; Coronary Angiography; Coronary Thrombosis; Electrocardiography; Heart Conduction System; Humans; Male; Middle Aged; Myocardial Infarction; Treatment Outcome

Haemobilia is a rare cause of acute upper gastrointestinal bleeding and is often associated with a history of hepatic or biliary tract injury, tumor growth, hepatic artery aneurysm, cholecystitis, or hepatic abscess. We report a case of a 79-year-old women with haemobilia due to acenocoumarol overdosage. She has been, taking 12 mg acenocoumarol by mistake for 5 days before admission because of atrial fibrillation. INR was 20 during an admission. Ultrasonographic evaluation demonstrated hepatomegaly, cholelithiasis, thick sludge in gallbladder represented blood clots and also dilated biliary tract. Cholecystectomy was carried out. The cut section of gall bladder showed stone, haemolysed blood and blood clots. Choledochotomy showed only blood clots within the duct. The treatment lasted long period and patient died because of multiorgan insufficiency in the course of sepsis.

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Cholecystectomy; Cholecystitis, Acute; Cholelithiasis; Drug Overdose; Fatal Outcome; Female; Hemobilia; Humans; Medication Errors; Multiple Organ Failure; Pancreatitis; Polyps; Splenectomy; Treatment Failure

The number of patients receiving oral anticoagulant therapy has increased markedly in recent years, with the consequence that monitoring must be decentralized. The aim of this study was to provide reference values for the quality of care in patients receiving oral anticoagulants at large specialized Spanish centers for use in future comparative analyses.. The records of 20,347 outpatients who were receiving oral anticoagulants between January and December 2003 at four large Spanish centers were assessed. Databases at the four hospitals were searched for severe adverse events.. In total, 211,987 regular check-ups were carried out, 72.7% of which gave international normalized ratios (INRs) within the range 2-4. Overall, 2369 hemorrhagic events were observed, 190 (8%) of which were severe, with 20 deaths (0.1 per 100 patient-years). In addition, there were 299 thromboembolic events, with 11 deaths (0.05 per 100 patient-years). The frequency of these events was greater in patients with a cardiac prosthesis, who required more intense anticoagulation. The incidence of death with different diagnoses was also greater in anticoagulated patients with a cardiac prosthesis, and the highest probability of death (1 in 3) was associated with episodes of cerebral hemorrhage. The incidence of hemorrhage increased as the INR increased. In contrast, thrombotic events occurred principally when the INR was below 2, and were not observed with INRs over 6.. The incidence of adverse events in patients receiving oral anticoagulant therapy at large Spanish centers was similar to that observed in other European countries.

Topics: Acenocoumarol; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chi-Square Distribution; Child; Female; Heart Valve Prosthesis; Hemorrhage; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Quality Indicators, Health Care; Regression Analysis; Spain

Patients with atrial fibrillation taking either indirect anticoagulant acenocumarol or most often prescribed antiaggregant aspirin were followed for 1 year. The results have shown that therapy with acenocumarol lowers content of D-dimer, prevents formation and promotes lysis of left auricular thrombi and lowers risk of development of ischemic stroke in patients with atrial fibrillation and high risk of thromboembolism. Therapy with aspirin in a dose providing maximal suppression of platelet function, does not lower D-dimer levels, does not promote lysis of left auricular thrombi and is inferior to acenocumarol in prevention of ischemic stroke.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Blood Platelets; Female; Follow-Up Studies; Heart Diseases; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Count; Thrombocytosis; Thrombosis; Treatment Outcome

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; International Normalized Ratio; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies

Topics: Acenocoumarol; Aged; Anticoagulants; Atrial Fibrillation; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Salicylates; Thromboembolism; Treatment Outcome; Warfarin

Thromboembolic complications (cerebral infarction and system embolism) are the most threatening ones in patients with ciliary arrhythmia without valvular lesions. Transoesofhageal echocardiography is the method of choice in detection of left atrial auricle thrombosis, which is the main source of thromboembolism in this category of patients. Primary and secondary prevention of thromboembolic complications in patients with ciliary arrhythmia is a topical problem, still remaining unsolved. Administration of indirect anticoagulants, which are the preparations of choice, demands strict doctor's supervision and continuous laboratory monitoring. The study presents authors' own data, based upon the observation of patients treated with either warfarin or acenocumarol. The paper demonstrates equal efficiency of both cumarine anticoagulants. The frequency of haemorrhagic complications after 12-month therapy with either warfarin or acenocumorol in patients with ciliary arrhythmia without valvular lesions was comparable. Warfarin provided more stable level of anticoagulation and thus long-term warfarin therapy was characterized by lower risk of complication.

Topics: Acenocoumarol; Adult; Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Middle Aged; Primary Prevention; Prospective Studies; Risk Factors; Thromboembolism; Time Factors; Warfarin

Topics: Acenocoumarol; Atrial Fibrillation; Humans; Patient Compliance; Treatment Outcome; Vitamin K

To obtain an impression of the extent and quality of the anti-coagulation treatment with coumarin derivatives carried out by the Thrombosis Services in the Netherlands.. Descriptive.. Data were drawn from the medical annual reports of 62 of the 63 Thrombosis Services in the Netherlands over the period 1998-2002. In 2002 the Thrombosis Services treated 325,072 patients and performed 4,469,730 INR laboratory tests. The half-yearly figures produced by the Thrombosis Services were calculated as an average percentage per year per thrombosis service and then recalculated as a percentage per year.. Seventy-three per cent of the patients were treated for an arterial and 27% for a venous indication. Depending on the required intensity of anticoagulation a mean of 74-78% of the long-term treated patients fell within the therapeutic range and a mean of 6-10% below. The mean number of major bleedings per 100 treatment years was 1.0. A mean of 79% of the patients was treated with acenocoumarol and 21% with phenprocoumon. When acenocoumarol was used, a mean of 72-77% fell within the therapeutic range and in the case of phenprocoumon 79-82%. In the last few years the number of patients had increased due to a growing number of patients treated for atrial fibrillation. The percentages of INR within the therapeutic range were unchanged or showed a slight increase.. The quality of the anticoagulation therapy with coumarin derivatives was good or acceptable.

Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Coumarins; Hemorrhage; Humans; International Normalized Ratio; Netherlands; Phenprocoumon; Quality of Health Care; Thrombosis; Treatment Outcome

To assess frequency of left auricular thrombosis and effect of long-term therapy with acenocoumarol on auricular hemodynamics and system of hemostasis and to elucidate predictors of effective therapy with acenocoumarol in patients with nonvalvular atrial fibrillation.. Patients (n=100) with nonvalvular atrial fibrillation and at least 1 risk factor of thromboembolic complications.. Transesophageal echocardiography and measurement of blood D-dimer levels were carried out before and after 1 year of acenocoumarol therapy.. Initial prevalence of left auricular thrombosis was 75%. The use of acenocoumarol for 12 months resulted in significant reduction of frequency of left auricular thrombosis. This was associated with improvement of parameters of intraatrial hemodynamics and lowering of elevated blood D-dimer levels. Clinical-instrumental predictors of presence of left auricular thrombosis and its dynamics during therapy with acenocoumarol were also elucidated.

Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Follow-Up Studies; Hemodynamics; Humans; Prospective Studies; Thrombosis

Recently there are several evidence based facts about the beneficial effect of oral anticoagulant therapy in patients with cardiovascular diseases. In the other hand the often serious bleeding complications as well as the ineffective antithrombotic therapy should be avoided.. Authors had examined with a questionnaire some characteristic parameters of oral anticoagulant therapy in Hungarian hospitals. Based on the results they carried out a retrospective survey (488 consecutive patients) on the accuracy and other peculiarity of long-term acenocoumarol therapy in the district of County Hospital Gyula.. Mean value of all coagulation test's results (INR: 2.72 +/- 1.07, prothrombin %: 36.11 +/- 10.52) suggest a relatively favourable therapeutic activity in the patients required acenocoumarol therapy. According to their data the proportion of newly introduced anticoagulant therapy secondary to atrial fibrillation was highly increased (42%). They stated that the accuracy of documentation in conducting of oral anticoagulant therapy should be improved and it would be the time to use obligatory the INR value in the clinical practice. They found the best therapeutic punctuality among the patients controlled in the Special Cardiological Outpatient Department. There were relatively few event of serious bleedings. The authors called attention to the patients (about 5%) who were treated without any special cause for a longer period of time than it was necessary. They emphasize the pivotal role of permanent education of patients and the importance of their therapeutic compliance in the appropriate oral anticoagulant control.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Heart Valve Prosthesis; Hemorrhage; Humans; Hungary; International Normalized Ratio; Male; Middle Aged; Outpatients; Patient Compliance; Patient Education as Topic; Prothrombin; Quality of Health Care; Retrospective Studies; Surveys and Questionnaires; Thromboembolism; Venous Thrombosis

Topics: Acenocoumarol; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; International Normalized Ratio; Male; Middle Aged; Mitral Valve Stenosis; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Salicylates; Warfarin

A SPORTIF-III substudy.. Warfarin has been considered to provide more stable anticoagulant effect than acenocoumarol due to its longer half-life.. The aim of this SPORTIF-III substudy was to compare acenocoumarol (A) with warfarin (W) in the same group of 74 patients, with chronic atrial fibrillation who started with W and then changed to A.. We compared prospectively a 3 months period on W with a 3 months period on A.. The mean number of INR measurements per patient was 5.7 +/- 1.2 and 5.4 +/- 1.6 resp (NS). The mean percentage of INR-s in the therapeutic range of 2-3 was 49 +/- 22.6% for W and 56 +/- 26.8% for A (p < 0.05), the percentage of subtherapeutic values were not different, the supratherapeutic values however occurred more frequently on W (28 +/- 20%) than on A (19 +/- 19%), p < 0,001. There was a good correlation between A and W doses (r = 0.65, p < 0.001), the mean W dose was 5.03 +/- 1.99 mg, the mean A dose was 2.5 +/- 1.3 mg, the W/A dose ratio was computed to be 2.18 +/- 0.78.. 1. anticoagulation effect stability was superior for A compared to W; 2. W/A dose ratio was 2.18.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Treatment Outcome; Warfarin

Over the last years, the use of oral anticoagulant treatment (OAT) has increased dramatically, principally for the prevention of embolic stroke in patients with atrial fibrillation. This study was aimed at evaluating the efficacy and safety of the management of OAT in a real-practice situation.. Nine hundred and three consecutive unselected patients, 250 of whom with atrial fibrillation, referred for the control of OAT to the Anticoagulation Clinic of the University of Florence were studied. The total follow-up period was 1679 patient-years.. The rate of major bleeding events was 0.8 per 100 patient-years in atrial fibrillation patients. In patients with a target INR > or = 3 a significantly higher rate of bleeding (p = 0.02) with respect to patients with a target INR < 3 was observed.. A low incidence of complications may be obtained even in elderly atrial fibrillation patients on OAT followed in an Anticoagulation Clinic specifically devoted to this management.

Topics: Acenocoumarol; Administration, Oral; Age Distribution; Aged; Aged, 80 and over; Ambulatory Care; Anticoagulants; Atrial Fibrillation; Case-Control Studies; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Electrocardiography; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Italy; Male; Middle Aged; Probability; Prospective Studies; Reference Values; Risk Assessment; Sampling Studies; Severity of Illness Index; Sex Distribution; Treatment Outcome; Warfarin

This retrospective study was performed to develop a model to predict the maintenance dosage of the vitamin K antagonist acenocoumarol, based upon the first INR after a standard initial dosage regimen.. Outpatients with atrial fibrillation ( n = 284) and initial regimens of 6-4 or 6-4-2 mg acenocoumarol on day 1, 2 and 3, respectively, were included. The maintenance dosage of the period 3-6 months after the installment was related to the first INR after those standard initial dosage regimens, because in that period the INR was 76% of the time within the therapeutic range and therefore considered suitable to perform the analysis.. A clear relation was found between the first INR, the maintenance dosage and the age. A model that predicts the maintenance dosage immediately after the standard initial dosage and based on the first INR and adjusted for age, has been developed, according to the formula: required dosage = 5.03-1.65 * ln (first INR) - 0.01 * age.. We have developed a formula to predict the maintenance dosage of acenocoumarol. With this formula it is possible to install this maintenance dosage and thus achieve oral anticoagulant therapy within the therapeutic range at an earlier stage. This will have to be shown in a prospective study.

Topics: Acenocoumarol; Administration, Oral; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Disease Management; Drug Monitoring; Humans; International Normalized Ratio; Middle Aged; Models, Theoretical; Multivariate Analysis; Predictive Value of Tests; Prognosis; Retrospective Studies

Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Circadian Rhythm; Factor VII; Factor VIIa; Humans; Stroke; Thrombolytic Therapy

The effect of acenocoumarol on hemorheological variables was measured in 35 non-valvular chronic atrial fibrillation patients before starting oral anticoagulant therapy (basal) and one and two months after beginning treatment (INR-2,3). Fibrinogen increased significantly from the basal situation: 332+/-99 mg/dl to 386+/-96 mg/dl in the second month (p<0.05). However, this small increase in fibrinogen is not large enough to mediate other rheological changes, and whole blood filterability, blood viscosity, plasma viscosity and erythrocyte deformability and aggregability remained unchanged after treatment. These results suggest that acenocoumarol does not affect rheological parameters and can therefore be used as a "neutral drug" for rheological studies in cardiovascular patients under oral anticoagulant therapy.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Atrial Fibrillation; Blood Viscosity; Drug Evaluation; Erythrocyte Indices; Female; Fibrinogen; Hemorheology; Humans; International Normalized Ratio; Male; Middle Aged; Prospective Studies; Safety

To investigate the risk factors determining the appearance of a new cardio-embolic cerebral accident on secondary thrombophylaxis of non-valvular auricular fibrillation (NVAF).. Controlled observational study on a series of patients treated with acenocoumarol for a period of 2.8 years.. Anticoagulation Unit of the La Paz Hospital and patients from Madrid Area 5.. 172 patients with NVAF, over 55 and with fibrillation for at least a year, and who had suffered at least one ischaemic cerebral accident. All were treated with acenocoumarol and controlled at an INR of 2.5. The risk factors were determined and the appearance of new cardio-embolic phenomena was watched during the study period.. 12 cardio-embolic phenomena were recorded (11 CVA and one peripheral embolism). The univariate study showed there was a significant association between patients who suffered a new ictus and those who suffered heart failure (p < 0.05) and had a history of more than one ictus before the start of the study (p < 0.05). Multivariate analysis found that what had independent predictive value was having suffered more than one ictus.. The greatest threat for developing a new ischaemic CVA during anticoagulation in NVAF is having a history of two or more previous ictus, as if the tendency to recur was due to these patients having more extensive atherosclerosis.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Female; Humans; Intracranial Embolism; Male; Middle Aged; Risk Factors; Stroke

Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Fatal Outcome; Female; Humans; Liver Cirrhosis, Alcoholic; Middle Aged; Necrosis; Protein C Deficiency; Skin Diseases

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Blood Coagulation Factors; Chronic Disease; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Male; Middle Aged

Cholesterol crystal embolization is a well-known disorder resulting from release of cholesterol crystals from ulcerous atherosclerotic plaques. Gastrointestinal involvement occurs in about a third of cases, but it is usually asymptomatic. We report a case of an old woman with small bowel obstruction secondary to atheromatous embolism. She was treated by acenocoumarol for atrial fibrillation and pulmonary embolism. Two weeks before admission for small bowel obstruction, she had a watery diarrhea. After 3 weeks of parenteral nutrition, she underwent resection of the involved ileum. Pathological examination showed a small bowel stricture secondary to atheromatous embolism. Cholesterol emboli should be considered as a potential cause of small bowel obstruction in old patient who has taken anticoagulant therapy or after vascular invasive procedure.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Arteriosclerosis; Atrial Fibrillation; Embolism, Cholesterol; Female; Humans; Intestinal Obstruction; Intestine, Small; Ischemia; Pulmonary Embolism

Although the indications for oral anticoagulation (AO) in the treatment of cerebral vascular disease (CVD) are well established, their potential side effects continue to give cause for worry.. To describe the complications and ischemic relapses in patients treated with AO for secondary prevention of CVD of cardiac embolic origin.. We included 169 patients with embologenic cardiopathy who, following an CVD, were treated with AO and followed-up at our medical centre for at least three months. We recorded their past clinical history and risk factors, occurrence of vascular relapses (VR), complications involving hemorrhage (CH), and data regarding course and follow-up.. During an average follow-up of 50.3 months of a total of 707.9 patient/years, 20 VR (2.8% per year) were recorded; 15 of these were cerebro-vascular and mainly mild. We recorded 59 CH in 41 patients (8.3% per year) of which 6 were considered to be major. There was a 30% drop-out rate from follow-up at our centre, mainly due to death from other causes or to change of referral centre.. There is a low incidence of relapse and of complications (usually mild) following AO for the secondary prevention of CVD of cardio-embolic origin. Efficacy and security are maintained in the long term.

Topics: Acenocoumarol; Administration, Oral; Alcoholism; Anticoagulants; Arteriosclerosis; Atrial Fibrillation; Cardiomyopathy, Dilated; Cohort Studies; Comorbidity; Diabetes Mellitus; Disease-Free Survival; Follow-Up Studies; Heart Valve Diseases; Hemorrhage; Humans; Hyperlipidemias; Hypertension; Intracranial Embolism and Thrombosis; Life Tables; Myocardial Infarction; Recurrence; Risk Factors; Smoking; Spain; Treatment Outcome

Transvenous internal cardioversion of chronic AF using a right atrium (RA) coronary sinus (CS) vector requires more energy than cardioversion of paroxysmal AF. Chronic AF is not terminated in 25% of patients using biphasic shocks up to 10 J. We therefore evaluated efficacy, safety, and tolerability of internal cardioversion using a "unipolar" configuration (RA to skin patch) and biphasic shocks in patients with long-lasting AF and different heart disease. In each patient, biphasic R wave synchronous shocks were delivered between a large defibrillating surface area electrode in the RA and a skin patch in the left prepectoral position. Defibrillation protocol started with a test shock of 0.4 J. Shocks were repeated and increased until termination of AF or a maximum of 34 J. Sedation was used when the patient described the shock as painful. This study included 11 patients with a mean age of 67 +/- 8 years (range 56-83). AF duration was > or = 1 month in all patients with a mean duration of 11 +/- 11 months (range 2-36). Underlying heart disease was present in all patients and the mean left atrial dimension was 43 +/- 9 mm (range 26-57). AF was terminated in 10 of 11 patients (91%) with a mean delivered energy of the successful shocks of 18.7 +/- 8.7 J (median energy 16.9 J; range 7.3-32.5) and a mean leading edge voltage of 564 +/- 129 V. The mean shock impedance at the defibrillation threshold was 71 +/- 13 omega (range 59-103). A total of 131 shocks were delivered without any complication and proarrhythmia episodes. We conclude that low energy "unipolar" internal cardioversion is a simple, safe, and effective technique for termination of chronic AF in patients with heart disease. The procedure is often tolerated under light sedation.

Topics: Acenocoumarol; Aged; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Chronic Disease; Electric Countershock; Electrocardiography; Electrodes, Implanted; Female; Humans; Male

The aim of the present study was to evaluate the impact of the results of clinical trials on the prophylactic treatment of non-rheumatic atrial fibrillation with oral anticoagulants.. Retrospectively, we studied a random sample of 375 patients discharged from our hospital with a diagnosis of non-rheumatic atrial fibrillation between 1991 and 1993. Information about diagnoses, other clinical variables and treatments prescribed at discharge was obtained from the hospital medical records.. During the whole study period, 14% of patients were prescribed an oral anticoagulant agent and 17% were prescribed acetylsalicylic acid. A non-significant increase in the proportion of patients prescribed oral anticoagulant drugs, from 9% to 17%, was observed. Multivariate analysis showed that a history of stroke (OR = 5.96) and younger age were significantly associated with the prescription of oral anticoagulants. ASA prescription was strongly associated with a history of concomitant vascular disease (OR = 5.8), but not with other risk factors for stroke. Sixty-five percent of patients had one or more risk factors for stroke, did not present any contraindications to anticoagulant agents, but nevertheless were not prescribed one of these drugs.. Anticoagulant agents and acetylsalicylic acid were largely underprescribed to patients with non-rheumatic atrial fibrillation, and oral anticoagulants were not prescribed according to the individual patients' risk of stroke.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Clinical Trials as Topic; Contraindications; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors

The aim of this study was to investigate the factors related to the presence of left atrial spontaneous echo contrast in mitral valve disease, and to ascertain whether it is a predictor of thromboembolism. One hundred and one patients (47 men, 54 women) with a mean age of 57.04 +/- 10.6 years who underwent transthoracic and transesophageal echocardiography were included in the study. Forty-five (44.5%) had isolated or predominant mitral valve stenosis, 12 (11.9%) predominant mitral insufficiency and 44 (43.6%) had had previous mitral valve replacement. Left atrial spontaneous echo contrast was detected by transesophageal echocardiography in 58 patients, while the transthoracic approach detected it in only 15 (14.9%) (P < 0.0001). An atrial thrombus was found in six cases, with a history of recent systemic embolism in three of them. There was no thrombus in the left atria of a further nine patients, despite definitive histories of recent systemic embolism. The finding of left atrial spontaneous echo contrast was related to the presence of atrial fibrillation or enlarged left atrium, the severity of mitral stenosis and the absence of significant mitral insufficiency. Anticoagulant therapy was not significantly associated with spontaneous left atrial echo contrast, but a stepwise linear regression analysis showed that its presence was the only independent predictor of thromboembolism (p < 0.0001). We conclude that left atrial spontaneous echo contrast in mitral valve disease can be discovered mainly by transesophageal echocardiography, and is correlated with factors which are associated with low left atrial blood flow velocity such as atrial fibrillation, enlarged left atrium, mitral stenosis of increased severity and the absence of significant mitral insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acenocoumarol; Adult; Aged; Atrial Fibrillation; Echocardiography; Echocardiography, Doppler; Echocardiography, Transesophageal; Female; Heart Atria; Heart Valve Prosthesis; Hemodynamics; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Stenosis; Postoperative Complications; Prosthesis Design; Regression Analysis; Risk Factors; Thromboembolism

Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cerebral Infarction; Female; Humans; Male; Middle Aged