phenprocoumon and Atrial-Fibrillation

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

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

Topics: Ambulatory Care; Anticoagulants; Atrial Fibrillation; Blood Coagulation Tests; Drug Monitoring; General Practice; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; International Normalized Ratio; Phenprocoumon; Postoperative Complications; Pulmonary Embolism; Thromboembolism; Venous Thrombosis

Electrical cardioversions are performed to restore sinus rhythm in patients with non-valvular atrial fibrillation to improve symptoms. It has been known for decades that cardioversion without adequate anticoagulation for 3-4 weeks prior to and for 4 weeks after cardioversion results in thromboembolic complication of about 5%. It is much less known that cardioversion is also associated with a higher risk of thromboembolism (stroke, peripheral embolism) in patients treated with usual anticoagulation. The control arms (warfarin) of the three studies with the new anticoagulants dabigatran, rivaroxaban, and apixaban for the prevention of thromboembolism in non-valvular atrial fibrillation report a monthly thromboembolic risk of 0,13-0,2%. The risk for thromboembolic complication in the month following cardioversion is about three to six times higher than without cardioversion in patients with non-valvular atrial fibrillation treated with usual anticoagulation. Since most cardioversions are performed by DC shock it is not known whether electrical and pharmacological cardioversions carry the same risk for thromboembolism. Although thromboembolic complications do not often occur following cardioversion the increased risk due to this procedure should be acknowledged. Strict anticoagulation (e. g. INR value > 2,5) in the first 10-14 days following cardioversion could possibly minimize the risk of thromboembolism.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Administration Schedule; Electric Countershock; Enoxaparin; Heparin; Humans; International Normalized Ratio; Morpholines; Phenprocoumon; Practice Guidelines as Topic; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Stroke; Thiophenes; Thromboembolism; Warfarin

In numerous situations stroke physicians face a lack of evidence during their daily practice. In this report the authors address some of the difficult treatment decisions encountered in acute therapy and secondary prevention. Examples include off-label thrombolysis and prevention in high-risk situations. The available data from trials and registries are discussed, and personal views and recommendations are expressed.

Topics: Age Factors; Aged; Aged, 80 and over; Antihypertensive Agents; Atrial Fibrillation; Blood Glucose; Cerebral Hemorrhage; Clinical Trials as Topic; Diagnosis, Differential; Endarterectomy, Carotid; Epilepsy; Evidence-Based Medicine; Humans; Hypertension; International Normalized Ratio; Off-Label Use; Phenprocoumon; Platelet Aggregation Inhibitors; Registries; Risk Factors; Secondary Prevention; Stroke; Survival Analysis; Thrombolytic Therapy; Treatment Outcome

Antithrombotic medication can be performed by means of heparins (non-fractionated heparin, low molecular heparins) or the pentasaccharide Fondaparinux as well as with oral vitamin K antagonists. The use of a low molecular heparin is initially recommended for the sake of practicability and safety in case of patients suffering from deep venous thrombosis of the leg and pelvis with subsequent long-term oral medication using a vitamin K antagonist (Marcumar) for anticoagulation. The most frequent indications for long-term anticoagulation are deep leg and pelvis thromboses, pulmonary embolism with atrial fibrillation, artificial prosthetic valves and open oval foramen with ischaemic cerebral infarction. In case of patients with chronic atrial fibrillation it is expedient to initiate permanent anticoagulation according to a risk score. For the purpose of controlling oral anticoagulation it is recommended to employ the INR value in place of Quick's value because these data are better comparable. In case of atherothrombotic diseases secondary prevention will always indicate administration of a thrombocyte aggregation inhibitor. In such cases acetylsalicylic acid is recommended as the standard preparation.

Topics: Administration, Oral; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atherosclerosis; Atrial Fibrillation; Blood Coagulation Tests; Cerebral Infarction; Drug Therapy, Combination; Female; Fibrinolytic Agents; Fondaparinux; Heart Valve Prosthesis; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Polysaccharides; Preoperative Care; Prevalence; Primary Prevention; Pulmonary Embolism; Risk Factors; Sex Factors; Stroke; Time Factors; Venous Thrombosis

Non-vitamin K oral anticoagulants have become the standard therapy for preventing stroke and ischemic thromboembolism in most patients with atrial fibrillation (AF). The effectiveness and safety of non-vitamin K oral anticoagulants in patients on hemodialysis is not well known.. From June 2017 through May 2022, AXADIA-AFNET 8 (Compare Apixaban and Vitamin K Antagonists in Patients With Atrial Fibrillation and End-Stage Kidney Disease), an investigator-initiated PROBE (prospective randomized open blinded end point) outcome assessment trial, randomized patients with AF on chronic hemodialysis to either apixaban (2.5 mg BID) or the vitamin K antagonist (VKA) phenprocoumon (international normalized ratio, 2.0 to 3.0). The composite primary safety outcome was defined by a first event of major bleeding, clinically relevant nonmajor bleeding, or all-cause death. The primary efficacy outcome was a composite of ischemic stroke, all-cause death, myocardial infarction, and deep vein thrombosis or pulmonary embolism. Our hypothesis was that apixaban is noninferior to VKA.. Thirty-nine sites randomized 97 patients (30% women; mean age 75 years; mean CHA. In this randomized trial comparing apixaban and VKA in patients with AF on hemodialysis with long follow-up, no differences were observed in safety or efficacy outcomes. Even on oral anticoagulation, patients with AF on hemodialysis remain at high risk of cardiovascular events. Larger randomized trials are needed to determine the optimal anticoagulation regimen for patients with AF on hemodialysis.. URL: https://www.. gov; Unique identifier: NCT02933697.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Myocardial Infarction; Phenprocoumon; Prospective Studies; Pyridones; Renal Dialysis; Stroke; Treatment Outcome

Patients with end-stage kidney disease requiring maintenance haemodialysis treatment experience a dramatic cardiovascular morbidity and mortality. Due to the high atherosclerotic and arteriosclerotic burden and profound alterations in haemostasis, they frequently suffer and die from both thromboembolic and bleeding events. This is a particular concern in patients on haemodialysis with atrial fibrillation (AF). Controlled trials on the optimal anticoagulation in patients with AF on haemodialysis are not available. The randomised controlled phase IIIb AXADIA-AFNET 8 trial will evaluate the safety and efficacy of the factor Xa inhibitor apixaban in patients with AF requiring haemodialysis.. A total of 222 patients will be randomised in an open-labelled, 1:1 design to receive either apixaban 2.5 mg twice daily or dose-adjusted vitamin K antagonist therapy (target international normalised ratio 2.0-3.0). All patients will be treated and followed up for a minimum of 6 months up to a maximum of 24 months. The primary outcome is major or clinically relevant, non-major bleedings or death of any cause. Secondary outcomes include stroke, cardiovascular death and other thromboembolic events, thus exploring the efficacy of apixaban. The first patient was randomised in June 2017.. The study protocol was approved by the Ethical Committee of the Landesaertzekammer, Westfalen-Lippe and the Medical Faculty of the University of Muenster, Muenster, Germany (reference number: 2016-598 f-A). Written informed consent will be obtained from all patients prior to study participation, including their consent for long-term follow-up. AXADIA-AFNET 8 is an investigator-initiated trial. Sponsor is AFNET, Muenster, Germany. Study findings will be disseminated to Bristol-Myers Squibb, Munich, Germany, and Pfizer, Berlin, Germany, to the participating centres, at research conferences and in peer-reviewed journals.. NCT02933697,Pre-results.

Topics: Adult; Anticoagulants; Atrial Fibrillation; Female; Germany; Hemorrhage; Humans; Male; Outcome Assessment, Health Care; Phenprocoumon; Pyrazoles; Pyridones; Renal Dialysis; Renal Insufficiency, Chronic; Thromboembolism

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

Non-vitamin K antagonist oral anticoagulants (NOACs) are at least as effective and safe as vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF). All pivotal trials have compared NOACs to warfarin. However, other VKAs are commonly used, for instance phenprocoumon.. A retrospective cohort study using a German claims database assessed the comparative risks of bleeding leading to hospitalization during therapy with NOACs and phenprocoumon in AF patients. Endpoints consisted of major bleeding, gastrointestinal bleeding, and any bleeding. Data were collected from January 1, 2013 to March 31, 2015. Patients newly initiated on dabigatran, apixaban, rivaroxaban, or phenprocoumon were included. Hazard Ratios for bleeding events were derived from Cox proportional hazard models, adjusting for differences in baseline characteristics. Propensity score matching was performed as a sensitivity analysis.. A total of 35,013 patients were identified, including 3138 on dabigatran, 3633 on apixaban, 12,063 on rivaroxaban, and 16,179 on phenprocoumon. Patients prescribed apixaban or phenprocoumon were older compared to those on dabigatran or rivaroxaban and had a higher CHA. Apixaban therapy is associated with a significantly reduced risk of bleeding compared to phenprocoumon. Bleeding risk with dabigatran was similar to that of phenprocoumon but bleeding risk with rivaroxaban was higher.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Follow-Up Studies; Germany; Hemorrhage; Humans; Incidence; Male; Phenprocoumon; Product Surveillance, Postmarketing; Retrospective Studies; Stroke

Dabigatran etexilate, a direct thrombin inhibitor and non-vitamin K antagonist oral anticoagulant (NOAC), has been shown to effectively prevent thromboembolic events in patients with non-valvular atrial fibrillation (AF). However, there is a paucity of data on the antithrombotic efficacy and safety of dabigatran in the resolution of left atrial appendage (LAA) thrombi in AF patients.. The primary objective of the RE-LATED AF trial is to assess whether dabigatran results in a faster complete LAA thrombus resolution as compared to vitamin K antagonist phenprocoumon. Secondary objectives are to assess the impact of dabigatran on complete LAA thrombus resolution rate within 6 weeks of treatment and change in LAA thrombus volume under treatment. Furthermore, this study aims to assess and compare safety and tolerability of dabigatran vs. phenprocoumon.. The study is designed as a prospective, randomized, open-label, controlled, explorative, blinded endpoint (PROBE) trial. Patients with AF and left atrial appendage thrombus confirmed by transoesophageal echocardiography (TEE) will be randomized to receive either dabigatran (150 mg bid) or phenprocoumon (INR 2-3) for the resolution of LAA thrombus formation for at least 21 days. Thrombus resolution will be determined by TEE 3 weeks after treatment initiation and subsequently at weeks 4 and 6, if the LAA thrombus has not been resolved before. A total of 110 patients are planned to be randomized.. This is the first prospective, multicentre, randomized controlled clinical trial investigating safety and efficacy of a NOAC for the resolution of LAA thrombi in patients with non-valvular AF.

Topics: Anticoagulants; Antithrombins; Atrial Appendage; Atrial Fibrillation; Dabigatran; Echocardiography, Transesophageal; Humans; Phenprocoumon; Prospective Studies; Research Design; Thrombosis

Apixaban is increasingly used for stroke prevention in patients with atrial fibrillation. Data about the safety of left atrial radiofrequency ablation procedures under continuous apixaban therapy are lacking. We performed a matched-cohort study of patients undergoing left atrium ablation procedures for atrial fibrillation or left atrial flutter. For each patient on apixaban, 2 patients on phenprocoumon were matched by age, gender, and type of arrhythmia. The primary safety end point was a composite of bleeding, thromboembolic events, and death. We identified 105 consecutive patients (35 women; mean age 63 years) on apixaban and matched 210 phenprocoumon patients (70 women, mean age 64 years). The primary end point was met in 11 patients of the apixaban group and 26 patients of the phenprocoumon group (10.5% vs 12.3%, p = 0.71). Major bleeding complications occurred in 1 patient of the apixaban group and 1 patient of the phenprocoumon group (1% vs 0.5%, p >0.99). Minor bleeding complications were observed in 10 patients of the apixaban group and 25 patients of the phenprocoumon group (9.5% vs 11.9%, p = 0.61). No patient in either group experienced a thromboembolic event and no patient died. In patients on apixaban, no clinical variable was predictive for bleeding complications. Left atrial ablation procedures under continuous oral anticoagulation with apixaban are feasible and as safe as under continuous oral anticoagulation with phenprocoumon.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Cardiac Catheterization; Catheter Ablation; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Phenprocoumon; Pyrazoles; Pyridones; Retrospective Studies; Stroke; Thromboembolism; Treatment Outcome

A relevant number of patients receive triple therapy with clopidogrel, aspirin, and oral anticoagulation. Clopidogrel's efficacy on ADP induced platelet function may be influenced by concomitant antithrombotic therapies. Data regarding the effect of dabigatran on platelet function is limited to in vitro studies and healthy individuals.. The "Dabi-ADP-1" and "Dabi-ADP-2" trials randomized patients with atrial fibrillation to either dabigatran or phenprocoumon for a 2-week period. In Dabi-ADP-1 (n = 70) patients with clopidogrel therapy were excluded and in Dabi-ADP-2 (n = 46) patients had to be treated concomitantly with clopidogrel. The primary endpoint was ADP-induced platelet aggregation between dabigatran and phenprocoumon at 14 days. Secondary endpoints were ADPtest HS-, TRAP-, and COL-induced platelet aggregation.. There was no significant difference regarding the primary endpoint between both groups in either trial (Dabi-ADP-1: Dabigatran: 846 [650-983] AU × min versus phenprocoumon: 839 [666-1039] AU × min, P = 0.90 and Dabi-ADP-2: 326 [268-462] versus 350 [214-535], P = 0.70) or regarding the secondary endpoints, ADPtest HS-, TRAP-, and COL-induced platelet aggregation.. Dabigatran as compared to phenprocoumon has no impact on ADP-induced platelet aggregation in atrial fibrillation patients neither with nor without concomitant clopidogrel therapy.

Topics: Adenosine Diphosphate; Administration, Oral; Aged; Aged, 80 and over; Atrial Fibrillation; Clopidogrel; Dabigatran; Female; Follow-Up Studies; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation; Ticlopidine

Vitamin K1 (VK1) reverses the effects of vitamin K antagonists (VKAs). The literature shows that the bioavailability from solutions might be higher than that from tablets, possibly resulting in different effects.. To compare the bioavailability and effect on the International Normalized Ratio (INR) of 5-mg VK1 tablets and solution in three randomized clinical trials.. The bioavailability was determined in a crossover trial with 25 healthy volunteers. VK1 plasma concentrations were assessed at 0, 2, 4, 5, 6, 8, 10 and 24 h, and the area under the curve was higher in the solution group than in the tablet group (mean difference 365 μg L(-1) h, 95% confidence interval [CI] 230-501, P < 0.0001). In the other two trials, the effects of both formulations on the INR were measured at 0, 24 and 48 h. In the second trial, on 72 patients on phenprocoumon with planned invasive procedures, both formulations were similarly effective, because all patients reached an INR of < 2.0, which was the primary endpoint. In the last trial, on 72 patients on phenprocoumon with an INR of 7.0-11.0, the INR decreased slightly more in the solution group (4.7, 95% CI 4.3-5.1) than in the tablet group (4.2, 95% CI 3.8-4.6). The solution group had a 3.3-fold increased likelihood (95% CI 0.7-15.1) of reaching an INR of < 2.0 at 48 h. Additionally, the increases in VK1 concentrations were similar (tablets, 3.2 μg L(-1) ; solution, 3.4 μg L(-1) ; P = 0.99) after 24 h.. VK1 tablets are at least as clinically effective as the solution in countering VKAs.

Topics: Administration, Oral; Adult; Aged; Antifibrinolytic Agents; Atrial Fibrillation; Biological Availability; Cross-Over Studies; Female; Healthy Volunteers; Humans; International Normalized Ratio; Likelihood Functions; Male; Middle Aged; Phenprocoumon; Tablets; Venous Thrombosis; Vitamin K 1

The oral anticoagulant phenprocoumon, similar to other vitamin K antagonists, is characterized by pronounced interindividual variability in the doses needed to achieve the desired therapeutic effect. Previous studies assessed the effect of genetic and demographic covariates on empirical dose requirements of phenprocoumon to enable individualized dose prediction. The aim of the present study was to quantify major sources of interindividual variability separately on the pharmacokinetics and pharmacodynamics of phenprocoumon using a population pharmacokinetic-pharmacodynamic model.. A single steady-state blood sample was collected from 278 patients and assayed by liquid chromatography-tandem mass spectrometry for phenprocoumon and its metabolites. Genotyping was performed for variants of the cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex, subunit 1 (VKORC1) genes. Effects were quantified by international normalized ratio (INR). Data were analyzed simultaneously using NONMEM VII.. The model confirmed CYP2C9 and VKORC1 variants as the major predictors of variability in phenprocoumon concentrations and effects, together with body weight, age, comedication with CYP3A modifiers (i.e. inhibitors or inducers) and presence of atrial fibrillation. These covariates explained 50.0 % of the observed variability in the model parameters. Phenprocoumon clearance fractions mediated per CYP2C9 allele were 13.4, 9.5 and 5.7 mL/h for the 1, 2 and 3 variants, respectively. An additional clearance fraction of 5.3 mL/h was independent of CYP2C9 activity. Homozygous VKORC1 wild-type carriers were estimated to have a 2.13-fold higher phenprocoumon exposure requirement than homozygous 1173 C>T carriers to achieve the same effect on INR.. The model provides a deeper insight in the separate pharmacokinetic and pharmacodynamic parts of phenprocoumon action. Thus, it provides important information for individualized dose prediction, with the option to include further covariates not studied here with known effects on individual pharmacokinetic or pharmacodynamic processes.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Chromatography, Liquid; Cross-Sectional Studies; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Female; Genotype; Humans; International Normalized Ratio; Male; Middle Aged; Mixed Function Oxygenases; Models, Biological; Nonlinear Dynamics; Phenprocoumon; Tandem Mass Spectrometry; Vitamin K Epoxide Reductases

Managing oral anticoagulant treatment (OAT) is a challenge for patients and primary care providers. It requires a high level of patient knowledge and adherence. Studies have shown that insufficient adherence and a low level of patient knowledge about OAT are primary causes for complications. This trial is the first to evaluate the long-term effects of a complex practice nurse-based patient education program in comparison to a patient brochure only.. This trial will be a cluster-randomized controlled trial in 22 general practices (GPs) recruiting 360 patients with OAT. GPs will be randomized into an intervention group or a control group. A baseline questionnaire will assess pre-existing knowledge about OAT. The patients in the intervention group will be educated by a complex education program which consists of a video, a brochure and individual training by a practice nurse. The video gives information about OAT, nutrition, and instructions about how to manage critical situations. The brochure repeats the content of the video. After 4 to 6 weeks, the intervention will be recapitulated. The control group will receive the brochure only. After 6 months, questionnaires will be used in both groups to assess patient knowledge about OAT as well as patients' subjective feelings of safety. Separately, we will evaluate patient records, looking for documented complications and the time spent in the therapeutic range.. This trial will start in January 2011. This trial will evaluate the long-term effectiveness of a video-assisted education program on patients with OAT in comparison to a patient information brochure. Most previous studies have evaluated knowledge directly after an educational intervention. Our trial will look for long-term differences in basic knowledge of OAT. We expect that our complex patient education program effectively increases long-term basic knowledge about OAT. Although the population of our study is too small to observe differences in adverse effects, we expect to discover differences in secondary outcomes, such as the time spent in the therapeutic range.. Deutsches Register Klinischer Studien (German Clinical Trials Register): DRKS00000586Universal Trial Number (UTN U1111-1118-3464).

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Protocols; Cluster Analysis; General Practice; Humans; Medication Adherence; Nurses; Pamphlets; Patient Compliance; Patient Education as Topic; Phenprocoumon; Primary Health Care; Program Development; Surveys and Questionnaires; Teaching; Treatment Outcome; Videotape Recording

Oral anticoagulation is highly effective for secondary prevention of cardioembolic strokes in patients with atrial fibrillation (AF). There are no studies investigating timing and complications of different strategies for initiation of oral anticoagulation after acute stroke or transient ischaemic attack (TIA).. Patients of ten community hospitals participating in the prospective evaluation of medical effects of the Telemedical Project for Integrative Stroke Care (TEMPiS) were included. This observational evaluation was restricted to ischaemic stroke or TIA patients with AF who were started on Phenprocoumon treatment during in-hospital stay. Antithrombotic co-medication was dichotomized in heparin bridging (weight or partial thromboplastin time-adjusted heparin) or conventional treatment (antiplatelets and/or low-dose heparin or nil). Besides treatment-relevant extracranial bleeding, major complications were documented according to the European Atrial Fibrillation Trial definitions including vascular death, ischaemic or haemorrhagic stroke, systemic embolism, and myocardial infarction.. Between July 2003 and March 2005, 4,082 ischaemic stroke or TIA patients were admitted. AF was recorded in 961 patients (23.5%), of whom 376 (39.1%) received oral anticoagulation. In 229 of these patients oral anticoagulation was started in hospital, 150 (65.5%) with heparin bridging and 79 (34.5%) with conventional treatment. Patients with heparin bridging were younger, and had a longer in-hospital stay after adjustment for potential confounders (p = 0.01). Major complications were infrequent in both groups (2.0 vs. 2.5%; p = 1.0) as well as extracranial bleeding (3.3 vs. 1.2%; p = 0.43).. Initiation of oral anticoagulation after acute ischaemic stroke yielded low complication rates independent of antithrombotic co-medication. Heparin bridging was associated with a longer stay in acute care hospitals.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Drug Administration Schedule; Female; Fibrinolytic Agents; Germany; Heparin; Humans; Ischemic Attack, Transient; Length of Stay; Male; Phenprocoumon; Platelet Aggregation Inhibitors; Prospective Studies; Stroke; Treatment Outcome

Anticoagulation in cardioversion for atrial fibrillation is performed using unfractionated heparin and oral anticoagulants. TEE-guided cardioversion, after achievement of therapeutic anticoagulation (1-3 days), may be an alternative to the traditional procedure (3-week anticoagulation followed by cardioversion). The quality of anticoagulation in atrial fibrillation has not been investigated in a randomised trial with TEE-guided cardioversion. We analysed respective data from the ACE trial on the quality of conventional anticoagulation, where most participating centres chose the TEE-guided approach.. In a randomised, prospective, multicentre trial, we analysed the efficacy of unfractionated heparin plus phenprocoumon in 248 patients on an intention-to-treat basis. There were 2373 evaluable anticoagulation measurements (out of 2925 measurements) and 4 categories of anticoagulation quality (under-, target, over- and severe over-anticoagulation). Of patients with evaluable measurements, 88% received short-term anticoagulation (4 weeks) in TEE-guided cardioversion.. The median time to achieve therapeutic anticoagulation (aPTT> or =60 and <80 s or INR> or =2 and <3) was 3 days. Anticoagulation values were out of therapeutic range in 69.5% of measurements during 4- or 7-week follow-up, and never within therapeutic range in 10% of patients. Of the 15 primary endpoints observed (death, thromboembolism and major bleeding complications), only 3 were in patients with anticoagulation measurements within therapeutic range.. In this study setting, with predominance of 4 weeks anticoagulation in TEE-guided cardioversion for atrial fibrillation, therapeutic anticoagulation was reached within 3 days using conventional anticoagulation. Despite careful dose adjustments, anticoagulation was out of therapeutic range in almost 70% of total measurements and 80% of primary endpoints.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Electric Countershock; Enoxaparin; Heparin; Humans; International Normalized Ratio; Partial Thromboplastin Time; Phenprocoumon; Prospective Studies; Thromboembolism; Time Factors

To estimate, from the perspective of Statutory Health Insurance (SHI, third-party payer) in Germany, the economic consequences of using the subcutaneous low-molecular-weight heparin (LMWH) enoxaparin instead of intravenous unfractionated heparin followed by oral phenprocoumon (UFH/PPC) for anticoagulation in patients undergoing transesophageal echocardiography (TEE)-guided early electrical cardioversion (ECV) of persisting nonvalvular atrial fibrillation (AF) without intracardiac clot.. The incremental cost for the enoxaparin-based regimen versus the UFH/PPC-based regimen was chosen as the target variable. A decision-analytic model considering the in- and outpatient sectors was used to quantify the target variable. Resource use during in- and outpatient treatment was taken from the Anticoagulation in Cardioversion using Enoxaparin (ACE) trial and from expert interviews with cardiologists in Germany in order to reflect the day-to-day conditions of clinical practice. Costs were given by SHI expenses for inpatient treatment and for medical services, drugs, disposables, and laboratory tests during outpatient treatment. These costs were determined by multiplying utilized resource items by the price or tariff of each item based on German healthcare regulations for the reference period of 2003/2004. According to the ACE trial, the evaluation encompassed 28 (26-30) treatment days with two consecutive phases. Phase I with 5 (3-12) days comprised diagnostics, start of anticoagulation, and ECV. Phase II with the remaining days consisted of continued anticoagulation and patient monitoring. The dosage of enoxaparin was 1 mg/kg bodyweight twice daily in treatment phase I followed by 40 mg twice daily with a bodyweight <65 kg or 60 mg twice daily with a BW > or =65 kg in treatment phase II. The daily dosages of UFH by continuous infusion and overlapping PPC were adjusted to an International Normalized Ratio of 2.0-3.0 in treatment phase I followed by 2.25mg PPC once daily in treatment phase II. Patients with any comorbidity and complication level (CCL) and those with low comorbidity and complications expected to occur in rare cases only (low-risk patients) were analyzed separately. In each base-case analysis, exclusively point estimates of all respective model parameters were applied.. There were savings of 339 euro and 579 euro per patient receiving the enoxaparin-based regimen versus the UFH/PPC-based regimen in the case of patients with any CCL and of low-risk patients, respectively (1 euro approximate, equals $US1.25; first quarter 2004 values). In comprehensive sensitivity analyzes, the robustness of the model and its results was shown. First, the impact of the model parameters on the target variable for each patient group was quantified in a deterministic model. Secondly, the dependency of the target variable on random variables was described for each patient group using Monte Carlo simulation. Irrespective of the patient group, the cost weight and the base rate of hospitals for inpatient ECV in phase I turned out to have the greatest impact on the savings obtained by the enoxaparin-based regimen. In the case of patients with any CCL, this impact was about 1.4-fold of that of the probability of enoxaparin patients undergoing outpatient ECV in phase I. In the case of low-risk patients, the impact of the cost weight and the base rate of hospitals for inpatient ECV in phase I was about 4.1-fold of that of the price of enoxaparin 60 mg prefilled syringes in the outpatient sector. In 79% and 93% of 10,000 simulated comparisons each versus the UFH/PPC-based regimen, there were savings obtained by the enoxaparin-based regimen in patients with any CCL and in low-risk patients, respectively.. Results of this evaluation showed that an enoxaparin-based regimen for TEE-guided ECV of AF in patients without intracardiac clot offers SHI in Germany a considerable saving potential when used instead of an UFH/PPC-based regimen.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Decision Support Techniques; Drug Therapy, Combination; Echocardiography, Transesophageal; Electric Countershock; Enoxaparin; Female; Germany; Heparin; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Phenprocoumon; Prospective Studies; Thromboembolism; Treatment Outcome

Patients (pts.) with atrial fibrillation (AF) and atrial thrombi are known to have an increased risk for cerebral embolism. However, little is known about the clinical course of atrial thrombi and the incidence of cerebral embolism in those patients during anticoagulation therapy. The high sensitivity of MR imaging (MRI) including diffusion-weighted imaging (DWI) suggests that this technique could provide an improved estimate of cerebral embolism associated with the presence of left atrial thrombi. The aims of this prospective study were to evaluate 1) the prevalence of clinically silent and apparent cerebral embolism in pts. with newly diagnosed AF and atrial thrombi using MRI/DWI, 2) the long-term fate of atrial thrombi under continues anticoagulation therapy and 3) the incidence of cerebral embolism during a follow-up period of 12 months with continuous anticoagulation therapy.. The study group consisted of 32 pts. with 1) newly diagnosed AF and evidence of left atrial (LA) thrombi detected by TEE and 2) a new start of anticoagulation therapy [International Normalized Ratio (INR) 2.0 - 3.0]. 19 pts. with 1) newly diagnosed AF and no evidence of atrial thrombi and 2) an equivalent anticoagulation regimen served as the control group. In both groups a) MRI/DWI studies of the brain (weeks 0, 4, 8, 12, 20, 28, 36, 44, and 52), b) transesophageal echocardiographic studies (TEE) for assessment of LA-Thrombi (weeks 0 and 52) and c) clinical neurological assessments (weeks 0, 20 and 52) were performed.. In the study group (AF and LA-Thrombi) 11 out of 32 pts. (34 %) displayed signs of acute (n = 8) or chronic (n = 3) cerebral embolism in the initial MRI studies. In 4 out of 32 pts. (13 %), MRI/DWI depicted new or additional cerebral emboli (n = 12) during the follow-up period despite continuous anticoagulation therapy. 2 (n = 2/4; 50 %) of these patients had clinically apparent neurological deficits. In the control group 1 out of 19 pts. (5 %) showed evidence of chronic cerebral embolism as assessed by MRI/DWI at the beginning of the study (week 0). No embolic cerebral lesions were detected during the 12-month follow-up. Within 12 months only 63 % (n = 20/32) of LA thrombi in the study group resolved completely under anticoagulation.. 1. The incidence of clinically inapparent cerebral emboli in pts. with newly diagnosed AF and atrial thrombi is much higher than the incidence of clinically apparent emboli and has been underestimated in the past. 2. New cerebral embolism may occur even with continued effective anticoagulation therapy in 13 % of pts. 3. Only 63 % of atrial thrombi resolve completely within 12 months under anticoagulation therapy.

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Cerebral Infarction; Diffusion Magnetic Resonance Imaging; Echocardiography, Transesophageal; Female; Follow-Up Studies; Heart Atria; Heart Diseases; Heparin; Humans; Incidence; Intracranial Embolism; Magnetic Resonance Imaging; Male; Middle Aged; Partial Thromboplastin Time; Phenprocoumon; Prospective Studies; Risk Factors; Sensitivity and Specificity; Thrombosis; Time Factors

Anticoagulation in cardioversion of atrial fibrillation is currently performed with unfractionated heparin (UFH) and oral anticoagulants, with or without guidance by transesophageal echocardiography (TEE). Low-molecular-weight heparins may reduce the risk of bleeding, may obviate the need for intravenous access, and do not require frequent anticoagulation monitoring.. In a randomized, prospective multicenter trial, we compared the safety and efficacy of enoxaparin administered subcutaneously with intravenous UFH followed by the oral anticoagulant phenprocoumon in 496 patients scheduled for cardioversion of atrial fibrillation of >48 hours' and < or =1 year's duration. Patients were stratified to cardioversion with (n=431) and without (n=65) guidance by TEE. The study aimed to demonstrate noninferiority of enoxaparin compared with UFH+phenprocoumon with regard to the incidence of embolic events, all-cause death, and major bleeding complications. Secondary end points included successful cardioversion, maintenance of sinus rhythm until study end, and minor bleeding complications. Of 496 randomized patients, 428 were analyzed per protocol. Enoxaparin was noninferior to UFH+phenprocoumon with regard to the incidence of the composite primary end point in a per-protocol analysis (7 of 216 patients versus 12 of 212 patients, respectively; P=0.016) and in an intention-to-treat analysis (7 of 248 patients versus 12 of 248 patients, respectively; P=0.013). There was no significant difference between the 2 groups in the number of patients reverted to sinus rhythm.. Enoxaparin is noninferior to UFH+phenprocoumon for prevention of ischemic and embolic events, bleeding complications, and death in TEE-guided cardioversion of atrial fibrillation. Its easier application and more stable anticoagulation may make it the preferred drug for initiation of anticoagulation in this setting.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Drug Therapy, Combination; Electric Countershock; Enoxaparin; Female; Hemorrhage; Heparin; Humans; Incidence; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Phenprocoumon; Safety; Thromboembolism; Treatment Outcome

Cardioversion (CV) in atrial fibrillation can cause arterial embolism. Effective anticoagulation clearly reduces the risk. In practice, in every third case anticoagulation is not in line with the recommendations. Simplification can be achieved, and time gained, by transesophageal echocardiography (TEE) due to the shorter anticoagulation period prior to CV, and by use of low-molecular-weight heparin (LMWH) for anticoagulation. As yet little data is available on LMWH in cardioversion. The aim of this cohort study was to investigate the administration of a LMWH in this indication under everyday clinical conditions.. 125 patients treated as inpatients for atrial fibrillation or -flutter received the LMWH Fragmin (dalteparin 2 x 100 anti-Xa units/kg, maximum dosage 2 x 10,000 anti-Xa units subcutaneously). In the presence of a relevant indication, TEE-guided CV was performed. The application of dalteparin was terminated as soon as effective anticoagulation had been achieved from phenprocoumon or once anticoagulation was no longer indicated.. 125 patients with atrial fibrillation or -flutter received dalteparin for a median of 11 days (range of 3-41 days). TEE was performed in 39 patients. Five patients revealed a thrombus in the left atrial appendage in the TEE, and one patient died from suspected cerebral embolism over the further course. In the remaining 124 patients, no thromboembolic event was established. Successfully cardioverted were 26 of 34 patients (76%) who had no thrombus in the TEE. Serious adverse effects did not ensue.. Simple, well tolerated and effective anticoagulation is possible with dalteparin in TEE-guided CV. Due to the methodic limitations of a cohort study and the low incidence of emboli, the efficacy of dalteparin in this indication needs to be further confirmed by prospective and randomized studies.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Atrial Flutter; Cohort Studies; Dalteparin; Dose-Response Relationship, Drug; Drug Administration Schedule; Echocardiography, Transesophageal; Electric Countershock; Female; Humans; Injections, Subcutaneous; Intracranial Embolism; Male; Middle Aged; Phenprocoumon; Premedication; Risk Factors; Thromboembolism; Treatment Outcome

The modality and duration of anticoagulation before, during, and after cardioversion of atrial fibrillation--either with or without guidance by transesophageal echocardiography (TEE)--is still an unresolved issue. Intravenous infusion of unfractionated heparin until effective anticoagulation with phenprocoumon or warfarin is used as the standard therapy. However, this approach may be associated with several days of hospitalization because of the necessity for intravenous heparin administration. Moreover, there may be an increased risk of bleeding complications or, conversely, episodes of undercoagulation. Low-molecular weight heparin is an attractive alternative as it not only provide a safe and predictable level of anticoagulation with fewer side effects but can also be administered safely on an outpatient basis. In addition, no anticoagulation monitoring is needed. The ACE study (Anticoagulation in Cardioversion using Enoxaparin) is a randomized, prospective, open-label multicenter trial comparing the safety and efficacy of subcutaneous enoxaparin with intravenous heparin/oral phenprocoumon before and after cardioversion (stratified to TEE guidance or no TEE guidance). This article presents the rationale, design and status of the ACE study.

Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Atrial Fibrillation; Dose-Response Relationship, Drug; Drug Administration Schedule; Echocardiography, Transesophageal; Electric Countershock; Enoxaparin; Female; Heparin; Humans; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Phenprocoumon; Prospective Studies; Pulmonary Embolism; Risk Factors; Treatment Outcome; Venous Thrombosis

We sought to assess in outpatients with atrial fibrillation and oral anticoagulation (1) whether the complication rate is influenced by the presence of the risk factors age >65 years, arterial hypertension, diabetes, or previous stroke; (2) whether the complication rate is influenced by the number of additional drugs taken by patients; and (3) whether problems and interventions differ between patients with or without complications.. - Clinical characteristics, drugs, problems, interventions, and complications were registered during 2 years.. - Three hundred sixty patients (mean age, 68 years; 43% female) were observed for 383 patient-years. Patients aged >65 years had more serious, life-threatening, or fatal complications (11% versus 5.3%/100 patient-years; P=0.0428) than younger patients. Patients with diabetes had more life-threatening and fatal complications (2.8% versus 0.6%/100 patient-years; P=0.0354) than patients without. The complication rate did not differ regarding the presence of previous stroke or hypertension. Patients who took 3 drugs per day have an increased complication rate and thus need especially careful monitoring of oral anticoagulation, including adequate pain control.

Topics: Administration, Oral; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Endpoint Determination; Female; Hemorrhage; Humans; Intracranial Embolism; Male; Middle Aged; Phenprocoumon; Risk Assessment; Risk Factors; Stroke

Direct oral anticoagulants (DOACs) were introduced based on randomised controlled trials (RCTs) comparing them to vitamin-K-antagonist (VKA) warfarin. In Germany, almost exclusively phenprocoumon is used as VKA. RCTs with phenprocoumon being absent we analysed the benefits and harms of DOACs and phenprocoumon for patients with atrial fibrillation (AF) in a real-world setting.. In a retrospective observational cohort study, claims data covering inpatient and outpatient care from 2015 to 2019 were analysed by Cox regression and propensity score matching (PSM).. Data from a group of small-sized to medium-sized health insurance companies in Germany.. We analysed datasets of 71 961 patients with AF and first prescription of phenprocoumon (n=20 179) or DOAC in standard dose (n=51 782). Patients with reduced dose of DOACs were excluded (n=21 724).. Outcomes were thromboembolic events, major bleeding and death during a 12-month follow-up period.. The regression analysis widely showed similarity between phenprocoumon and standard dose DOACs regarding effectiveness and safety. There were only three statistically significant differences: a lower bleeding risk with composite DOACs and apixaban (HR (95% CI) = 0.67 (0.59 to 0.76) and 0.54 (0.46 to 0.63), respectively) and a higher risk of death with rivaroxaban (1.21 (1.10 to 2.34)). The analysis after PSM was consistent with the first two results regarding composite DOACs and apixaban (number needed to treat, NNT 101 and 78) and showed a lower bleeding risk with rivaroxaban (NNT 156). Absolute differences were small.. The small superiority or non-inferiority of DOACs over warfarin seen in the RCTs might not translate into relevant advantages of DOACs over phenprocoumon. To confirm the hypothesis, an RCT with phenprocoumon is needed. Next to the safety and effectiveness assessments other factors might also play a substantial role in the decision on the right OAC for stroke prevention.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Phenprocoumon; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Vitamins; Warfarin

Atrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC).. We performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004. In 2011-17, 227 707 AF patients initiated treatment with a DOAC or PPC, of which 1828 cases developed epilepsy on current treatment with an oral anticoagulant. They were matched to 19 084 controls without epilepsy. Patients with DOAC treatment for AF had an overall higher risk of epilepsy with an odds ratio of 1.39, 95% CI (1.24; 1.55) compared to current PPC treatment. Cases had higher baseline CHA2DS2-VASc scores and more frequently a history of stroke than controls. After excluding patients with ischaemic stroke prior to the diagnosis of epilepsy, the risk of epilepsy was still higher on DOACs than on PPC. In contrast, within a cohort of patients with venous thromboembolism, the risk of epilepsy on treatment with DOACs was less elevated [adjusted odds ratio 1.15, 95% CI (0.98; 1.34)].. In patients with AF initiating oral anticoagulation, treatment with a DOAC was associated with an increased risk of epilepsy compared to the vitamin K antagonist PPC. Covert brain infarction may explain the observed elevated risk of epilepsy.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Case-Control Studies; Humans; Phenprocoumon; Risk Factors; Stroke; Vitamin K

Atrial fibrillation is the most important risk factor for left atrial appendage (LAA) thrombi, a potentially life-threatening condition. Thrombus resolution may prevent embolic events and allow rhythm-control strategies, which have been shown to reduce cardiovascular complications.. There is no significant difference between phenprocoumon and non-Vitamin K-dependent oral anticoagulants (NOACs) in the resolution of LAA-thrombi in a real-world setting.. Consecutive patients with LAA-thrombi from June 2013 to June 2017 were included in an observational single-center analysis. The primary endpoint was defined as the resolution of the thrombus. The observational period was 1 year. Resolutions rates in patients on phenprocoumon or NOACs were compared and the time to resolution was analyzed.. We identified 114 patients with LAA-thrombi. There was no significant difference in the efficacy of resolution between phenprocoumon and NOACs (p = .499) at the time of first control which took place after a mean of 58 ± 42.2 (median 48) days. At first control most thrombi were dissolved (74.6%). The analysis after set-time intervals revealed a resolution rate of 2/3 of LAA-thrombi after 8-10 weeks in the phenprocoumon and NOAC groups. After 12 weeks a higher number of thrombi had resolved in the presence of NOAC (89.3%) whereas in the presence of phenprocoumon 68.3% had resolved (p = .046).. In this large observational study NOACs were found to be potent drugs for the resolution of LAA-thrombi. In addition, the resolution of LAA-thrombi was found to be faster in the presence of NOAC as compared to phenprocoumon.

Topics: Administration, Oral; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Echocardiography, Transesophageal; Humans; Phenprocoumon; Thrombosis

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

Patients taking oral anticoagulants (OACs) currently represent one-third of all patients treated for epistaxis and an upward trend is expected. New direct oral anticoagulants (DOACs) have been on the market for approximately 10 years. DOACs are favoured over Vitamin K-Antagonists (VKAs) in the current guidelines. There are barely studies that investigate the impact of DOACs on patients with epistaxis. A retrospective study was performed analysing all patients who had stationary treatment for epistaxis from 01.01.2011 to 01.01.2018 in a tertiary care centre. In a total of 466 patients, 46.1% were on OACs. The main indication was atrial fibrillation (AF, 67.4%).The number of DOACs taken surpassed that of the VKAs during the past 2 years. The length of hospital stay was significantly longer in the phenprocoumon group (3 ± 0.2 days) in comparison to both the rivaroxaban (2.3 ± 0.1) and the apixaban (2.2 ± 0.1) groups (p = 0.005). Posterior epistaxis occurred more frequently in the phenprocoumon group (10.8%) than in the rivaroxaban (0%) and apixaban (0%) groups (p = 0.03). A correlation between CHA

Topics: Aged; Anticoagulants; Atrial Fibrillation; Epistaxis; Factor Xa Inhibitors; Female; Humans; Length of Stay; Male; Middle Aged; Phenprocoumon; Pyrazoles; Pyridones; Retrospective Studies; Risk Assessment; Rivaroxaban

Geriatric characteristics such as high age, multi-morbidity, polypharmacy and frailty are common in patients with atrial fibrillation (AF). In a retrospective study using a German claims database, effectiveness (ischaemic stroke/systemic embolism) and safety (intracerebral, gastrointestinal and major extracranial bleeding) were compared in patients with non-valvular AF starting non-vitamin K oral antagonists (NOACs) (apixaban, dabigatran and rivaroxaban) and phenprocoumon. Cox proportional hazards models were used to calculate adjusted hazard ratios, and interaction terms of the treatment group and geriatric status (defined by age ≥75 years, frailty, ≥ 4 co-morbidities and polypharmacy) were entered into the model. A total of 42,562 and 27,939 patients initiated NOAC and phenprocoumon treatment (mean age 74 years ± 11, 51% male) with a follow-up time of 147,785 person-years. Note that 52.9% of patients were elderly, 50.8% were frail, 37.0% were co-morbid and 46.5% had polypharmacy. NOAC use was not associated with effectiveness and gastrointestinal bleeding, neither in geriatric nor in non-geriatric patients. The hazard of major extracranial and intracranial bleeding was significantly decreased for NOAC use, with similar risk reduction in geriatric and non-geriatric patients: major extracranial bleeding 0.70 (95% confidence interval [CI], 0.56-0.87) to 0.73 (95% CI, 0.60-0.89) for the geriatric groups and 0.71 (95% CI, 0.56-0.93) to 0.76 (0.59-0.98) for the non-geriatric groups (

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dabigatran; Female; Geriatrics; Germany; Humans; Middle Aged; Phenprocoumon; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Vitamin K

Several studies showed reduced stroke severity in patients with atrial fibrillation (AF) if the international normalized ratio (INR) was ≥ 2 at stroke onset. There are no respective data for non-vitamin K-dependent oral anticoagulants (NOACs). The aim of this study was to compare the impact of NOAC or phenprocoumon intake on stroke severity.. In this single-centre observational study, 3669 patients with acute ischaemic stroke were retrospectively analysed regarding AF status and medication immediately before admission. Using multivariable regression, we analysed the association of pre-admission anticoagulation with severe stroke (National Institutes of Health Stroke Scale score ≥ 11) on admission and poor outcome at discharge (modified Rankin scale score > 2). Before the index stroke, 655 patients had known AF and a CHA2DS2-VASc score ≥ 2. While 325 (49.6%) patients were anticoagulated, 159 (24.3%) were prescribed a NOAC and 75 (11.5%) phenprocoumon patients had an INR ≥ 2 on admission. Compared with AF patients without medical stroke prevention, an INR ≥ 2 [OR 0.23 (95% CI 0.10-0.53)] or NOAC intake [OR 0.48 (95% CI 0.27-0.86)] were associated with a lower probability of severe stroke after adjustment for confounders, while an INR < 2 [OR 0.62 (95% CI 0.33-1.16)] was not. Adjusted odds ratios for poor functional outcome at hospital discharge were 0.47 (95% CI 0.27-0.84) for NOAC patients, 0.33 (95% CI 0.17-0.65) for INR ≥ 2 and 0.61 (95% CI 0.32-1.16) for INR < 2.. NOAC intake before stroke did reduce the probability of severe stroke on hospital admission and poor functional outcome at hospital discharge as similarly demonstrated for phenprocoumon patients with an INR ≥ 2 on admission.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Female; Hospitalization; Humans; International Normalized Ratio; Male; Phenprocoumon; Protective Factors; Retrospective Studies; Risk Factors; Severity of Illness Index; Stroke; Time Factors; Treatment Outcome

Information on utilization of oral anticoagulants (OACs) in nursing homes is scarce. This study aimed to (i) describe OAC use in German nursing home residents, (ii) examine factors influencing whether treatment is initiated with vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) and (iii) assess which conditions predict switching to NOAC instead of continuing VKA.. Using claims data (2010-2014), we studied a cohort of new nursing home residents aged ≥65 years receiving OAC. Further, OAC use in patients with atrial fibrillation (AF) was examined over the years.. Overall, 16 804 patients (median age: 85 years, 75% female, 44% with renal disease) were included. The majority received phenprocoumon as first OAC (58.0%), followed by rivaroxaban (28.1%). Over the study period, NOAC use increased substantially. Initiating NOAC instead of VKA was predicted by a previous stroke (adjusted odds ratio: 1.76; 95% confidence interval: 1.49-2.08). In contrast, renal disease predicted VKA initiation (0.66; 0.59-0.75) as did the presence of a prosthetic heart valve. Switching from VKA to NOAC was predicted by a stroke (2.55; 2.00-3.24), bleeding events and a recent hospitalization. During 2010-2014, the proportion of AF patients with a CHADS2 score ≥2 receiving OAC increased from 27% to 46%.. NOACs are increasingly used in German nursing homes, both for initial anticoagulation but also in VKA pre-treated patients. Switching from VKA to NOAC was substantially influenced by aspects such as intended higher effectiveness and safety but probably also practicability due to less blood monitoring.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cohort Studies; Drug Monitoring; Female; Germany; Hemorrhage; Humans; Kidney Diseases; Male; Nursing Homes; Phenprocoumon; Rivaroxaban; Stroke; Vitamin K

Data about the safety of edoxaban in patients who underwent left atrial (LA) radiofrequency (RF) ablation procedures are lacking. This study sought to compare the safety of uninterrupted edoxaban with uninterrupted phenprocoumon administration during LA RF ablation for atrial fibrillation and atrial tachycardia. In total, 231 patients (mean age 64 ± 11years, male 71%) who underwent LA RF ablation under continuous oral anticoagulation (OAC) with edoxaban or phenprocoumon were included in the study. Patients on uninterrupted edoxaban (60 mg or 30 mg/day for at least 4 weeks) were matched for gender, age and type of arrhythmia with 2 patients on uninterrupted phenprocoumon (international normalized ratio 2 to 3). We identified 77 consecutive patients on edoxaban and n = 154 patients on phenprocoumon. Heparin was administered periprocedurally to achieve an activated clotting time of 280 to 300 seconds. No protamine was administered periprocedurally. The primary end point was a composite of bleeding, thromboembolic events, and death. The primary end point was met in 9 patients in the edoxaban group and in 22 patients in the phenprocoumon group (p = 0.69). No patient in either group died or had a thromboembolic complication. No major bleeding complication was observed in the edoxaban group, whereas one was found in 1 patient in the phenprocoumon group (p ≥0.99). Minor bleeding complications occurred in 9 patients (12%) in the edoxaban group and in 21 patients (14%) in the phenprocoumon group (p = 0.84). Uninterrupted OAC with edoxaban appeared to be as safe as uninterrupted OAC with phenprocoumon in patients who underwent LA RF ablation procedures.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Electrocardiography; Factor Xa Inhibitors; Female; Humans; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Pulmonary Veins; Pyridines; Radiofrequency Ablation; Thiazoles; Treatment Outcome

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Comorbidity; Dabigatran; Female; Hemorrhage; Humans; Male; Middle Aged; Patient Safety; Phenprocoumon; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Treatment Outcome

The effect of direct oral anticoagulants (DOACs) on turbidimetric measurements of plasma clot formation and susceptibility to fibrinolysis may facilitate a comparison between different classes of anticoagulants in plasma samples. We obtained 424 citrate plasma samples from 226 atrial fibrillation patients on anticoagulation and 24 samples without anticoagulation serving as controls. As comparators, we measured the international normalized ratio (INR) for phenprocoumon samples (N = 166), anti-Xa for low molecular weight heparin (LMWH) samples (N = 42), and DOAC levels with mass spectrometry (dabigatran N = 40, rivaroxaban N = 110, apixaban N = 42). Plasma clot formation and lysis were recorded continuously on a photometer after addition of an activation mix (tissue factor 2 pmol/l and tissue plasminogen activator 333 ng/ml). We used linear regression and ANCOVA for correlation analysis. Clot formation lag phase was prolonged in the presence of anticoagulants in a concentration-dependent manner for DOACs (dabigatran Spearman r = 0.74; rivaroxaban r = 0.78; apixaban r = 0.72, all p < 0.0001), INR dependent for phenprocoumon (r = 0.59, p < 0.0001), anti-Xa level dependent in LMWH samples (r = 0.90, p < 0.0001). Maximum rate of clot formation and peak clot turbidity were reduced in the presence of anticoagulants, but correlated only moderately with the comparator measures of anticoagulation. The clot lysis time was inversely correlated with DOAC concentrations in the presence of recombinant thrombomodulin. A direct ex vivo comparison between the effects of different classes of anticoagulants is possible with turbidimetric measurement of plasma clot formation and lysis. Anticoagulation inhibited clot formation in a plasma concentration manner for DOACs, INR dependent for phenprocoumon, and anti-Xa dependent for LMWH. Susceptibility to fibrinolysis increased with increasing DOAC concentrations.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Case-Control Studies; Dabigatran; Factor Xa Inhibitors; Female; Fibrin Clot Lysis Time; Heparin, Low-Molecular-Weight; Humans; Linear Models; Male; Middle Aged; Phenprocoumon; Plasma; Pyrazoles; Pyridones; Rivaroxaban; Thromboplastin; Tissue Plasminogen Activator

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Phenprocoumon; Warfarin

The pivotal trials for stroke prevention in non-valvular atrial fibrillation (NVAF) compared rivaroxaban, dabigatran, and apixaban with warfarin, as did most claims-based studies. Comparisons with phenprocoumon, the most frequently used vitamin K antagonist (VKA) in Germany, are scarce.. Risk of bleeding, ischemic stroke, and all-cause mortality in patients with NVAF were analyzed using data for 2010 to 2014 from a large German claims database. New users of oral anticoagulants from January 2012 to December 2013 were included and observed over 1 year. Baseline characteristics were adjusted using propensity score matching and logistic regression. Several sensitivity analyses were carried out.. Fifty-nine thousand four hundred forty-nine rivaroxaban, 23,654 dabigatran, 4894 apixaban, and 87,997 matched phenprocoumon users were included. Adjusted hazard ratios (95% confidence intervals) compared with phenprocoumon were as follows: hospitalized bleedings: rivaroxaban 1.04 (0.97; 1.11), dabigatran 0.87 (0.77; 0.98), and apixaban 0.65 (0.50; 0.86); ischemic stroke: rivaroxaban 1.05 (0.94; 1.17), dabigatran 1.14 (0.96; 1.35), and apixaban 1.84 (1.20; 2.84); all-cause mortality: rivaroxaban 1.17 (1.11; 1.22), dabigatran 1.04 (0.95; 1.13), and apixaban 1.14 (0.97; 1.34).. With rivaroxaban, no significant differences were observed compared to phenprocoumon with regard to hospitalized bleedings or ischemic strokes. Dabigatran was associated with fewer bleedings and a similar risk of ischemic strokes compared to phenprocoumon. Apixaban was also associated with fewer bleedings but was unexpectedly associated with more ischemic strokes, possibly reflecting selective prescribing. The association of rivaroxaban with higher all-cause mortality unrelated to bleedings or strokes has been described previously but remains to be explained.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Databases, Factual; Female; Follow-Up Studies; Germany; Hemorrhage; Humans; Male; Middle Aged; Phenprocoumon; Stroke; Vitamin K; Young Adult

Novel oral anticoagulation (NOAC) has been introduced in recent years, but data on use in atrial fibrillation (AF) in primary care setting is scarce. In Germany, General Practitioners are free to choose type of oral anticoagulation (OAC) in AF. Our aim was to explore changes in prescription-rates of OAC in German primary care before and after introduction of NOAC on the market.. Data of a representative morbidity registration project in primary care in Germany (CONTENT) were analysed. Patients with AF in 2011 or 2014 were included (before and after broad market authorization of NOAC, respectively). We defined three independent groups: patients from 2011 without follow-up (group A), patients from 2014 but without previous record in 2011 (group B) and patients with AF and records in 2011 and 2014 (group C).. 2642 patients were included. Group A (n = 804) and B (n = 755) were comparable regarding patient characteristics. 87.3% of group A and 84.8% of group B had CHA. In summary, our study showed a significant increase of OAC over time, which is fostered by the use of NOAC but with a stable rate of VKA and a sharp decrease of ASA. Patients on VKA are rarely switched to NOAC, but new patients with AF are more likely to receive NOAC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Cross-Sectional Studies; Dabigatran; Female; Germany; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Primary Health Care; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Young Adult

Topics: Adrenomedullin; Adult; Aged; Ankle Brachial Index; Anticoagulants; Asymptomatic Diseases; Atrial Fibrillation; Atrial Natriuretic Factor; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Female; Fibrinogen; Germany; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Phenprocoumon; Protein Precursors; Pulmonary Embolism; Risk Factors; Stroke; Stroke Volume; Vascular Stiffness; Venous Thrombosis; Warfarin

We aimed to assess the efficacy and safety of vitamin K antagonist (VKA) monotherapy in atrial fibrillation (AF) patients undergoing transcatheter aortic valve implantation (TAVI).. In 735 TAVIs since 2008 we identified 167 patients suffering from concomitant AF who received either VKA monotherapy (n=77), VKA plus single antiplatelet therapy (SAPT, n=41) or a triple anticoagulation regimen (n=49). Thromboembolic as well as bleeding complications were analysed for six months after TAVI. Only one minor bleeding and no thromboembolic events occurred after VKA therapy had been initiated post TAVI. Compared to patients being treated with additional either single or dual antiplatelet therapy, the incidence of major/life-threatening bleeding complications was significantly lower in the VKA mono group (0/77 [VKA mono] vs. 3/41 [VKA+SAPT; p=0.04] vs. 4/49 [triple anticoagulation; p=0.02]). Analysis of a combined endpoint of post-procedural death, stroke, embolism and major bleeding revealed a significant superiority of VKA monotherapy compared to VKA plus SAPT or DAPT, respectively (5/77 vs. 9/41 [p=0.02] vs. 14/49 [p=0.002]).. VKA therapy without additional antiplatelet treatment is effective and safe in AF patients undergoing TAVI.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Feasibility Studies; Female; Germany; Hemorrhage; Humans; Male; Phenprocoumon; Postoperative Complications; Thromboembolism; Transcatheter Aortic Valve Replacement

Data are limited on the safety of periprocedural anticoagulation with novel oral anticoagulants (NOACs) in patients undergoing pulmonary vein isolation (PVI) using the second-generation cryoballoon (CB) for the treatment of atrial fibrillation.. We hypothesized that the incidence of acute periprocedural complications in patients undergoing PVI do not differ between patients treated with VKA compared to NOACs.. In 200 consecutive patients (mean age, 64.3 _ 10.6 years; female, n = 83) with symptomatic atrial fibrillation, PVI using the second-generation 28-mm CB was performed. In patients treated with NOACs, the medication was stopped the day of the procedure and continued the evening after the procedure with a reduced dosage. Patients treated with phenprocoumon were continued on uninterrupted phenprocoumon with a target INR of 2 to 3. If INR was <2, bridging with low-molecular-weight heparin was performed.. Forty-seven of 200 patients (23.5%) were treated with a vitamin K antagonist (VKA) and 55 (27.5%) were treated with apixaban, 67 (33.5%) with rivaroxaban, and 31 (15.5%) with dabigatran. Seven (3.5%) major complications occurred in the overall population. Major bleeding complications did not differ significantly between the 2 groups (P = 0.23). One patient taking VKA had a pericardial tamponade at the end of the procedure; 2 patients treated with apixaban developed a groin hematoma requiring surgical intervention. Transient ischemic attack occurred in 1 patient of the apixaban and rivaroxaban group.. Apixaban, rivaroxaban, and dabigatran, compared with uninterrupted VKA, did not show a higher risk for major bleeding or ischemic complications in patients undergoing PVI using the second-generation CB.

Topics: Administration, Oral; Aged; Antithrombins; Atrial Fibrillation; Cardiac Catheters; Cerebrovascular Disorders; Cryosurgery; Dabigatran; Drug Administration Schedule; Drug Monitoring; Equipment Design; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Postoperative Hemorrhage; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Vitamin K

Topics: Administration, Oral; Amiodarone; Atrial Fibrillation; Drug Administration Schedule; Drug Therapy, Combination; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Parotid Gland; Perioperative Care; Phenprocoumon; Postoperative Complications; Pulmonary Embolism; Rivaroxaban

The aims of this study were to assess the impact of atrial fibrillation (AF) on outcome in transfemoral aortic valve replacement (TAVR) and to evaluate the safety and efficacy of apixaban compared with a vitamin K antagonist (VKA) in patients with AF after TAVR.. Non-VKA oral anticoagulant agents have not been systematically used in patients with AF after TAVR.. Of the 617 patients enrolled, 55.9% (n = 345) were in sinus rhythm and 44.1% (n = 272) in AF. Clinical follow-up was performed after 30 days and 12 months.. The early safety endpoint at 30 days was significantly more frequent in patients with AF compared with those in sinus rhythm (23.2% vs. 11.0%; p < 0.01). During 12-month follow-up, the secondary endpoint of all-cause mortality and stroke was significantly higher in patients with AF (20.6% vs. 9.7%; p = 0.02), driven by a significantly higher rate of all-cause mortality (19.1% vs. 7.8%; p = 0.01). Among patients with AF, 141 (51.8%) were treated with apixaban and 131 (48.2%) with a VKA. There was a significantly lower rate of the early safety endpoint in patients with AF treated with apixaban compared with patients treated with a VKA (13.5% vs. 30.5%; p < 0.01), with a numerically lower stroke rate (2.1% vs. 5.3%; p = 0.17) at 30 days and 12 months (1.2% vs. 2.0%; p = 0.73) of follow-up.. In patients undergoing TAVR, AF was associated with a significantly higher rate of all-cause mortality throughout 12 months follow-up. The early safety endpoint in patients with AF on apixaban was significantly less frequent compared with patients receiving a VKA.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Disease-Free Survival; Factor Xa Inhibitors; Female; Femoral Artery; Humans; Kaplan-Meier Estimate; Male; Phenprocoumon; Proportional Hazards Models; Prospective Studies; Punctures; Pyrazoles; Pyridones; Registries; Risk Factors; Stroke; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome; Vitamin K

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

Data on the novel oral anticoagulants (NOACS) during catheter ablation (CA) of atrial fibrillation (AF) are still limited. This study evaluated the periprocedural major complications (MC) of CA of AF, and compared Apixaban, Dabigatran, and Rivaroxaban with continuous phenoprocoumon.. A total of 444 patients (mean age = 65.1 ± 9.4 years; 283 [64%] male) with paroxysmal (n = 180 [41%]), persistent (n = 256 [58%]), or longstanding-persistent AF were enrolled. CA was performed in all patients using radiofrequency energy in conjunction with a 3D-mapping system. MCs were defined according to the current guidelines. Continuous phenprocoumon-therapy was administered in 120/444 (27%) patients (group 1) and 324/444 (73%) patients were treated with NOACs (group 2; Dabigatran: n = 51 [15.7%]; Rivaroxaban: n = 193 [59.6%]; Apixaban: n = 80 [24.7%]). Procedure times were comparable between groups 1 and 2 (128.2 ± 39.7 minutes vs. 129.7 ± 51.2 minutes; P = 0.77). CHA2 DS2-Vasc (3.0 [2.0, 4.0)] vs. 2.0 [1.0, 3.0]; P < 0.01) and HASBLED scores (2.0 [2.0, 2.5] vs. 2.0 [1.0, 2.0]; P = 0.002) were higher in group 1 patients. The incidence of MCs in the overall group was 8/444 (2%) and was equally distributed between groups 1 and 2 (2/120 [2%] vs. 6/324 [2%], P = 0.90). The incidence of MCs was comparable between the three different NOACs. There were no significant differences between patients with and without MCs with regard to age, CHA2 DS2-Vasc-score or HASBLED-score.. The major complication rate between all three NOACs currently available and continuous phenprocoumon during AF ablation seem to be comparable. Complication rates were similar between patients treated with the three different available NOACs.

Topics: Action Potentials; Administration, Oral; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Catheter Ablation; Dabigatran; Drug Administration Schedule; Electrophysiologic Techniques, Cardiac; Factor Xa Inhibitors; Female; Heart Rate; Humans; Male; Middle Aged; Phenprocoumon; Postoperative Complications; Pyrazoles; Pyridones; Registries; Rivaroxaban; Stroke; Time Factors; Treatment Outcome

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

Data evaluating the complications of pulmonary vein isolation (PVI) using second-generation cryoballoons (CB) related to different anticoagulation regimes are limited. This study evaluates the total complications and the impact of novel oral anticoagulants (NOACs) compared to phenprocoumon on adverse events in the setting of PVI using CB.. PVI was performed using second-generation CB by two experienced investigators. A total of 409 patients (58.9% male; mean age = 61 ± 10 years) with atrial fibrillation were included in this study. In group I, 150/409 (36.7%) patients received phenprocoumon therapy, and in group II, 259/409 (63.3%) patients were treated with NOACs (rivaroxaban: n = 193; dabigatran: n = 48; and apixaban: n = 18). In both groups, the rates of major complications were similar (group I [phenprocoumon]: four pts (2.7%) vs. Group II [NOACs]: seven pts (2.7%); P = 0.999). In this cohort, 275 patients were ablated with the bonus freeze protocol, and 134 patients were ablated without bonus freezes. The procedure duration significantly decreased with the bonus freeze protocol from 102.3 ± 24.6 min to 68.5 ± 16.2 min (P < 0.001). The impact of the bonus freeze on the postprocedural increase of C-reactive protein (CRP) levels was significant compared to the postprocedural CRP levels after procedures without the bonus freeze protocol (postprocedural CRP level+ bonus protocol: 1.6 ± 1.2 mg/L vs. postprocedural CRP level+ nonbonus protocol: 1.3 ± 1.3 mg/L; P = 0.04).. The incidence of adverse events in PVI using the second-generation CB with the periprocedural administration of NAOCs was not significantly different compared to phenprocoumon. Further, large-scale randomized studies are needed to evaluate the safety of two anticoagulation regimes comparing vitamin K antagonists and NOACs, as well as different NOAC regimes, in patients undergoing PVI using cryoballoon ablation.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Biomarkers; Cryosurgery; Dabigatran; Female; Germany; Humans; Incidence; Inflammation Mediators; Male; Middle Aged; Phenprocoumon; Postoperative Complications; Pulmonary Veins; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Treatment Outcome

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Guideline Adherence; Humans; Phenprocoumon; Stroke; Vitamin K

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

The direct oral anticoagulants (DOAC) dabigatran, rivaroxaban, and apixaban are increasingly prescribed in atrial fibrillation (AF) patients, although dosage in elderly patients, safety in chronic kidney disease, food- and drug-interactions, laboratory tests for monitoring, and antidote are not clarified. In a 78-year-old man with an acute stroke, paroxysmal AF and sick-sinus-syndrome were detected as he received a DDD-pacemaker and 5 mg apixaban/bid. He had a history of hypertension, hypothyroidism, diabetes mellitus, hyperlipidemia, sleep apnea, lumbar discopathy, and nephropathy. Renal function deteriorated after 2 months, and apixaban was changed to phenprocoumon. Three months later, he suffered from abdominal pain and hemorrhagic shock due to rupture of an infrarenal aortic aneurysm. After reversal of the anticoagulation with prothrombin-complex concentrate, a stent-graft with exclusion of the aneurysm was implanted. Switching from apixaban to phenprocoumon was probably life-saving. Vitamin-K-antagonists should be preferred to DOAC in patients with AF and vascular disease.

Topics: Aged; Anticoagulants; Aortic Aneurysm; Atrial Fibrillation; Drug Administration Schedule; Drug Substitution; Fibrinolytic Agents; Humans; Male; Phenprocoumon; Pyrazoles; Pyridones; Thrombosis; Treatment Outcome

Topics: Accidental Falls; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Atrial Fibrillation; Combined Modality Therapy; Diagnosis, Differential; Diverticulum; Female; Gastrointestinal Hemorrhage; Humans; Intestine, Small; Myocardial Infarction; Phenprocoumon; Stents

Topics: Aged, 80 and over; Atrial Fibrillation; Checklist; Diagnosis, Differential; Emergencies; Female; Gastritis; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Kidney Failure, Chronic; Phenprocoumon

Preadmission oral anticoagulant treatment (OAT) has been linked with less severe stroke and a better outcome in patients with atrial fibrillation. However, the existing studies have methodological limitations and have, with one exception, not included hemorrhagic strokes. We performed a nationwide historic follow-up study using data from population-based healthcare registries to assess the effect of preadmission OAT on stroke outcomes further.. We identified 11 356 patients with atrial fibrillation admitted to hospital with acute stroke (including ischemic stroke and intracerebral hemorrhage) between 2003 and 2009. Propensity score-matched analyses were used to compare stroke severity (Scandinavian Stroke Scale score) and mortality among 2175 patients with preadmission OAT and 2175 patients without preadmission OAT.. A total of 2492 (21.9%) patients received OAT at the time of their stroke. Preadmission OAT was associated with a lower risk of severe stroke (Scandinavian Stroke Scale score at time of admission, <30 point; propensity score-matched odds ratio, 0.74; 95% confidence interval, 0.63-0.86) and lower 30-day mortality rate (propensity score-matched adjusted odds ratio, 0.83; 95% confidence interval, 0.71-0.98).. Only a minority of hospitalized patients with acute stroke with atrial fibrillation received OAT at the time of stroke. Preadmission OAT was associated with less severe stroke and lower 30-day mortality rate in a propensity score-matched analysis.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Denmark; Educational Status; Emergency Medical Services; Female; Follow-Up Studies; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Phenprocoumon; Population; Risk Factors; Stroke; Treatment Outcome; Warfarin

The optimal long-term antithrombotic treatment of patients with coexisting atrial fibrillation and stable coronary artery disease is unresolved, and commonly, a single antiplatelet agent is added to oral anticoagulation. We investigated the effectiveness and safety of adding antiplatelet therapy to vitamin K antagonist (VKA) in atrial fibrillation patents with stable coronary artery disease.. Atrial fibrillation patients with stable coronary artery disease (defined as 12 months from an acute coronary event) between 2002 and 2011 were identified. The subsequent risk of cardiovascular events and serious bleeding events (those that required hospitalization) was examined with adjusted Cox regression models according to ongoing antithrombotic therapy. A total of 8700 patients were included (mean age, 74.2 years; 38% women). During a mean follow-up of 3.3 years, crude incidence rates were 7.2, 3.8, and 4.0 events per 100 person-years for myocardial infarction/coronary death, thromboembolism, and serious bleeding, respectively. Relative to VKA monotherapy, the risk of myocardial infarction/coronary death was similar for VKA plus aspirin (hazard ratio, 1.12 [95% confidence interval, 0.94-1.34]) and VKA plus clopidogrel (hazard ratio, 1.53 [95% confidence interval, 0.93-2.52]). The risk of thromboembolism was comparable in all regimens that included VKA, whereas the risk of bleeding increased when aspirin (hazard ratio, 1.50 [95% confidence interval, 1.23-1.82]) or clopidogrel (hazard ratio, 1.84 [95% confidence interval, 1.11-3.06]) was added to VKA.. In atrial fibrillation patients with stable coronary artery disease, the addition of antiplatelet therapy to VKA therapy is not associated with a reduction in risk of recurrent coronary events or thromboembolism, whereas risk of bleeding is increased significantly. The common practice of adding antiplatelet therapy to oral VKA anticoagulation in patients with atrial fibrillation and stable coronary artery disease warrants reassessment.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Cohort Studies; Comorbidity; Coronary Artery Disease; Drug Therapy, Combination; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Phenprocoumon; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Ticlopidine; 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

This study aimed to evaluate the safety of continuous periprocedural rivaroxaban administration during left atrial radiofrequency ablation (RFA) in comparison with uninterrupted oral vitamin K antagonist administration. Data about the use of rivaroxaban in the setting of left atrial RFA procedures are lacking.. The study cohort included 544 patients (mean age, 63±10 years) who underwent left atrial RFA procedures between February 2012 and May 2013. All patients (n=272) receiving uninterrupted periprocedural rivaroxaban 15 or 20 mg/d before the procedure (rivaroxaban) were matched by age, sex, and type of rhythm disorder with an equal number of patients managed with uninterrupted vitamin K antagonist phenprocoumon (international normalized ratio, 2-3). During RFA, heparin was given intravenously to maintain an activated clotting time at 270 to 300 s. The safety end point was a composite of bleeding, thromboembolic events, and death. There were no thromboembolic complications and no deaths in either group. The prevalence of major bleeding complications was similar in both groups (1 tamponade in RivG and 1 groin hematoma requiring transfusion in phenprocoumon). Minor bleeding complications occurred equally in both groups (20 of 272; 7% in the rivaroxaban versus 33 of 272, 12% in the phenprocoumon; P=0.08). In multivariable analyses, female sex was associated with a greater risk of complications (odds ratio, 1.96; 95% confidence interval, 1.10-3.49).. In patients undergoing left atrial RFA, continuous periprocedural rivaroxaban use seems to be as safe as uninterrupted periprocedural phenprocoumon administration.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Chi-Square Distribution; Drug Administration Schedule; Female; Germany; Heart Atria; Hemorrhage; Humans; Logistic Models; Male; Middle Aged; Morpholines; Multivariate Analysis; Odds Ratio; Phenprocoumon; Registries; Retrospective Studies; Risk Factors; Rivaroxaban; Sex Factors; Thiophenes; Thromboembolism; Time Factors; Treatment Outcome

Vitamin K antagonists not only influence the synthesis of coagulation factors but also the activation of other vitamin K dependent proteins. Among other possible side effects, arterial calcification has been focused on in recent years.. Four patients under long-term anticoagulation for more than 10 years developed medial calcific sclerosis. In case 1 we identified an unexplained medial calcific sclerosis on x-ray after a trauma by chance. After that we examined the ankle-brachial index of blood pressure in all patients who had received long-term anticoagulation for more than 10 years. Where the index exceeded 1,3 we performed a x-ray-examination of the forefoot. Of the four described patients no one suffered from diabetes mellitus, renal failure or hyperparathyreoidism. Serum calcium was normal in all patients. The severity of the medial calcific sclerosis could not be explained by the initial vascular risk factors.. In certain patients, even at low vascular risk, a medial calcific sclerosis can appear under long-term anticoagulation with vitamin K antagonists. We conclude that vitamin K antagonists inhibit several proteins which protect the vessels from calcification leading to medial calcific sclerosis.

Topics: Aged; Aged, 80 and over; Ankle Brachial Index; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Forefoot, Human; Heart Valve Prosthesis Implantation; Humans; Incidental Findings; Long-Term Care; Male; Middle Aged; Monckeberg Medial Calcific Sclerosis; Phenprocoumon; Postoperative Complications; Vitamin K

To investigate the cost-effectiveness of pharmacogenetic-guided phenprocoumon dosing versus standard anticoagulation care in Dutch patients with atrial fibrillation.. Using a decision-analytic Markov model, cost-effectiveness of pharmacogenetic-guided therapy versus standard care was estimated.. Compared with standard care, the pharmacogenetic-guided dosing strategy increased quality-adjusted life-years (QALYs) only very slightly and increased costs by €15. The incremental cost-effectiveness ratio was €2658 per QALY gained. In sensitivity analyses, the cost of genotyping had the largest influence on the cost-effectiveness ratio. In a probabilistic sensitivity analysis, the incremental costs of genotype-guided dosing were less than €20,000 per QALY gained in 75.6% of the simulations.. Pharmacogenetic-guided dosing of phenprocoumon has the potential to increase health slightly and may be able to achieve this in a cost-effective way. Owing to the many uncertainties it is too early to conclude whether or not patients starting phenprocoumon should be genotyped.

Topics: Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Cost-Benefit Analysis; Cytochrome P-450 CYP2C9; Decision Support Techniques; Genotype; Humans; Markov Chains; Pharmacogenetics; Phenprocoumon; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Drug Substitution; Factor Xa Inhibitors; Humans; Morpholines; Phenprocoumon; Rivaroxaban; Secondary Prevention; Stroke; Thiophenes; Thromboembolism; Warfarin

Spontaneous small-bowel hematomas most commonly involve the jejunum, followed by the ileum and duodenum, and occur in patients who receive excessive anticoagulation with phenprocoumon/warfarin or who have additional risk factors for bleeding. We report three cases of intramural small-bowel hematoma, all complications of treatment with phenprocoumon, which nowadays is used extensively for therapeutic and prophylactic purposes. Diagnosis can be readily attained by sonography and confirmed using computed tomography. Early diagnosis is crucial because most patients can be treated successfully without surgery. Based on this experience and data from the literature, conservative treatment is recommended for intramural intestinal hematomas, when other complications needing laparotomy have been excluded.

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cholangiopancreatography, Endoscopic Retrograde; Duodenal Diseases; Female; Gastrointestinal Hemorrhage; Hematoma; Humans; Image Enhancement; Intestine, Small; Jejunal Diseases; Magnetic Resonance Imaging; Male; Phenprocoumon; Tomography, X-Ray Computed; Ultrasonography

Although liver damage is a relatively rare adverse effect of oral anticoagulation with phenprocoumon, acute liver failure can be a serious treatment-associated complication. In this contribution, a patient with drug-induced liver failure during oral anticoagulation with phenprocoumon is presented. This case illustrates the need for close laboratory monitoring and suggests that phenrocoumon-induced liver damage should be considered along with other common complications of this treatment.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Humans; Liver Failure; Male; Phenprocoumon

A male with atrial fibrillation for 30 years underwent embolectomy in his right leg at age 78 years. Postoperatively, he received enoxaparin 60 mg/twice a day (bid), and on day 5, phenprocoumon was started. The patient's son, a general practitioner, changed phenprocoumon to dabigatran 110 mg/bid on day 8. Pain in his left calf induced readmission after 5 days. International normalized ratio was 2.5 and D-dimer was 20 μg/mL. Dabigatran was stopped and dalteparin 5000 International Units/bid and 40 μg alprostadil infusions were started. After 8 hours, he became comatose due to basilar artery occlusion and eventually died. This tragic case raises the issue of postoperative use of dabigatran, a recently introduced thrombin inhibitor.

Topics: Aged; Anticoagulants; Antithrombins; Arterial Occlusive Diseases; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cerebral Angiography; Dabigatran; Drug Monitoring; Drug Therapy, Combination; Embolectomy; Embolism; Enoxaparin; Fatal Outcome; Femoral Artery; Humans; International Normalized Ratio; Male; Phenprocoumon; Vertebrobasilar Insufficiency

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Approval; Drug Interactions; Drug Substitution; Factor Xa Inhibitors; Germany; Humans; Morpholines; Phenprocoumon; Rivaroxaban; Thiophenes; Thromboembolism

Topics: Aged; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Atrial Fibrillation; Comorbidity; Cytochrome P-450 CYP2C9; Denmark; Drug Monitoring; Female; Genotype; Humans; International Normalized Ratio; Linear Models; Male; Middle Aged; Outpatient Clinics, Hospital; Phenprocoumon; Prospective Studies; Severity of Illness Index; Stress, Psychological; Surveys and Questionnaires; Thrombophilia; Vitamin K; Warfarin

We report the case of a 83-year-old female patient with ST elevation myocardial infarction who developed a rectus sheath hematoma during treatment with antiplatelet medication and systemic anticoagulants following cough attacks. The patient presented with progressive pain in the left lower abdomen associated with a palpable mass and anaemia. Abdominal sonography and computed tomography revealed a rectus sheath hematoma. We discuss pathogenesis, clinical findings, diagnostic workup and therapy. Moreover, we review the current related literature.

Topics: Abdomen, Acute; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Colonic Pseudo-Obstruction; Comorbidity; Cough; Dalteparin; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hematoma; Humans; Intracranial Embolism; Phenprocoumon; Rectus Abdominis; Ticlopidine

Topics: Angioplasty, Balloon, Coronary; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Disease; Coronary Restenosis; Drug Interactions; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Phenprocoumon; Proton Pump Inhibitors; Stents; Thromboembolism; Ticlopidine

The case of a 78-year-old female patient who suffered atrial fibrillation and persistent thrombus in the left atrial appendage despite sufficient anticoagulation is reported. The case is chosen to demonstrate the complexity inherent in prophylaxis as well as risk evaluation of thromboembolism on the basis of clinical and echocardiographic criteria. We also discuss transesophageal echocardiography as the standard diagnostic procedure for detection of intracardiac thrombi prior to cardioversion as well as cardiac computer tomography as an alternative.

Topics: Administration, Oral; Adrenergic beta-Antagonists; Aged; Anticoagulants; Atrial Fibrillation; Drug Therapy, Combination; Echocardiography; Echocardiography, Transesophageal; Electric Countershock; Enoxaparin; Female; Heart Atria; Heart Diseases; Humans; International Normalized Ratio; Phenprocoumon; Risk Factors; Thromboembolism; Thrombosis; Tomography, X-Ray Computed

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Catheter Ablation; Humans; Patient Education as Topic; Phenprocoumon; Recurrence; Treatment Outcome

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Contraindications; Drug Therapy, Combination; Humans; Intracranial Embolism; Phenprocoumon; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Ticlopidine

Topics: Aged; Anticoagulants; Atrial Fibrillation; Atrioventricular Block; Diagnosis, Differential; Electrocardiography; Embolism; Female; Humans; Phenprocoumon; Risk Factors

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Dose-Response Relationship, Drug; Hemorrhage; Humans; Phenprocoumon; Pyridines; Randomized Controlled Trials as Topic; Stroke; Vitamin K

Topics: Administration, Oral; Age Factors; Aged; Anticoagulants; Atrial Fibrillation; Electric Countershock; Enoxaparin; Humans; International Normalized Ratio; Partial Thromboplastin Time; Phenprocoumon; Prospective Studies; Thromboembolism; Time Factors

Topics: Aged, 80 and over; Airway Obstruction; Anticoagulants; Atrial Fibrillation; Cough; Deglutition Disorders; Drug Overdose; Hematoma; Humans; Male; Neck; Phenprocoumon; Prothrombin Time; Skin Diseases; Venous Insufficiency

Topics: Aged; Anticoagulants; Atrial Fibrillation; Embolism; Emergencies; Heparin; Humans; Ischemia; Leg; Male; Patient Admission; Phenprocoumon; Treatment Refusal

The ablation of common type atrial flutter is mainly performed by two approved techniques, whose efficacy and outcome in terms of quality of life have not been evaluated so far in a long-term follow-up study over years. A high proportion of patients suffer from coexistent atrial fibrillation, which may worsen the ablation result. The question arises whether one technique is more effective than the other when immediate ablation results, the occurrence of atrial fibrillation and the quality of life are compared. Considering these facts, it is reasonable to think about new ablation strategies for common type atrial flutter in the era of new concepts in catheter ablation of atrial fibrillation.. In a retrospective study we evaluated a detailed questionnaire in 132 patients who underwent ablation of common type between 1999 and 2004. Radiofrequency ablation was performed irrespective of coexistent atrial fibrillation either with an irrigated tip or the 8 mm tip electrode. Acute and long-term ablation outcome, and the associated quality of life, pre-, under- and post-ablation was compared in the two different ablation groups. Recurrent tachycardia were re-evaluated by 12 lead ECG analysis and assessed for both ablation groups.. 88 (67%) of the 132 patients contacted answered the questionnaire polling the perceived benefits of the procedure. Of the other 44 patients (33%); 4 (3%) had died, 7 (5.3%) had moved, 33 patients (25%) could not be included due to missing or incoherent answers. Independent of the ablation technique there was a high acute and long-term ablation success rate at about 95%. After a mean of 3 years of follow-up this benefit persists in spite of a high proportion of recurrent tachycardia, mainly atrial fibrillation (55/88 patients, 59.1%). Despite the occurrence of secondary tachycardia, there was a high significant long-term symptomatic benefit in the state of healthy and daily practice work, evaluated with a p-value of < 0.0005. The frequency of episodes and the symptom "tachycardia" were significantly reduced after effective ablation of common type atrial flutter, p-values of 0.003 and 0.002, respectively. Therefore the need for hospitalization was significant reduced (p = 0.001). Comparison of both approaches revealed that there was no significant difference related to the incidence and occurrence of atrial fibrillation.. The two mainly accepted and applied techniques for the ablation of common type atrial flutter show an excellent outcome under the aspect of ablation efficacy and quality of life in longterm follow-up. Three years after the ablation procedure the majority of patients consider the intervention beneficial. Despite the relatively high appearance of atrial fibrillation in the long-term follow-up this effect is still traceable.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Atrial Flutter; Cardiac Electrophysiology; Catheter Ablation; Electrocardiography; Female; Follow-Up Studies; Hospitalization; Humans; Longitudinal Studies; Male; Middle Aged; Phenprocoumon; Quality of Life; Retrospective Studies; Surveys and Questionnaires; Tachycardia; Treatment Outcome

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Embolism; Female; Humans; Hyperthyroidism; Male; Phenprocoumon; Risk Factors; Thyroid Gland; Thyrotropin

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Combined Modality Therapy; Electric Countershock; Electrocardiography; Humans; Phenprocoumon; Recurrence; Treatment Outcome

A 66-year-old male was admitted to hospital due to painless jaundice. Because of ischemic cardiomyopathy with paroxysmal atrial fibrillation as well as recurrent ventricular tachycardias and fibrillation he was treated with phenprocoumon and amiodarone (200 mg per day) for 2 years. Laboratory tests revealed significant elevation of the parameters of cholestasis and aminotransferase activity. Serological tests excluded infectious, autoimmune or metabolic liver diseases. Abdominal ultrasound and ERCP showed no mechanic cholestasis nor tumor of the pancreas. Cardiac congestive disease was also excluded. Severe intrahepatic cholestasis, consistent with drug-induced hepatotoxic damage, was diagnosed histologically. After discontinuing phenprocoumon the liver enzymes further increased. When amiodarone was stopped, however, laboratory parameters showed a continuous downward tendency. For prevention of malignant cardiac arrhythmia the patient received an atrioventricular defibrillator. Intrahepatic cholestasis is a rare presentation of amiodarone-induced hepatic toxicity. Liver damage can even occur after the drug has been taken for prolonged periods without any problems.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cholestasis, Intrahepatic; Humans; Male; Phenprocoumon; Severity of Illness Index; Treatment Outcome

Drug therapy should be individualized according to criteria of efficacy, adverse effects, and treatment adherence. This is particularly important at the interface of inpatient and ambulatory care. Aspects of drug approval (labeling) and individual refunding by health care insurance should also be taken into account.. A patient (male, 61 years, painter) showed elevated transaminases after treatment with phenprocoumon because of a deep vein thrombosis in 1999. Transaminases normalized completely after discontinuation of phenprocoumon. Other reasons for the elevated transaminases could be excluded. After a recurrent thrombosis in 2003 phenprocoumon was prescribed again followed by recurrent elevation of transaminases and subsequent cholestatic hepatitis progressing to fulminant hepatic failure that required liver transplantation. After transplantation the patient's general state of health was good and liver function nearly normal. Anticoagulation was indicated beyond the postoperative phase because of recurrent deep vein thrombosis and atrial fibrillation. A low-molecular-weight heparin was chosen for long-term treatment.. A low-molecular-weight heparin appears to be the most appropriate way to maintain effective and safe anticoagulation in this patient. Coumarins carry a residual risk of an extrahepatic, immunologically mediated cross-sensitization. Long-term use of ximelagatran may also cause liver damage. For heparinoids, hirudins, and other drugs affecting coagulation like platelet aggregation inhibitors, therapeutic evidence is not sufficient. Though subcutaneous application of heparin is a disadvantage for the patient, therapeutic alternatives do not have better documented efficacy or less hepatotoxic potential. The low-molecular-weight heparin fulfills the criteria for refunding set by federal jurisdiction.

Topics: Anticoagulants; Atrial Fibrillation; Drug Approval; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; Liver Failure; Liver Function Tests; Liver Transplantation; Long-Term Care; Male; Middle Aged; Phenprocoumon; Postoperative Complications; Recurrence; Treatment Outcome; Venous Thrombosis

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

A 61-year-old woman was referred because of painless jaundice, laboratory tests having indicated hepatitis with impaired liver functions. For the past two years she had been taking phenprocoumon because she had atrial fibrillation.. Serological tests largely excluded infectious, autoimmune or metabolic etiology, so that the diagnosis of drug-induced hepatic disease was made. Liver biopsy showed necrotic liver cells and mild inflammatory reaction.. A perforating duodenal ulcer required urgent surgical intervention, after which liver functions further deteriorated. The patient having refused liver transplantation she was treated symptomatically (oral vitamin K. lactulose, diuretics), phenprocoumon was discontinued and her condition slowly improved. She was discharged after two months. At subsequent examination she was symptom-free, the INR was 1.41, transaminases were normal and ultrasound merely showed a slightly inhomogeneous internal structure.. Phenprocoumon can cause liver damage even when the drug has been taken for prolonged periods without any problems. A careful history about previously administered drugs should be taken in any case of hepatitis of uncertain etiology.

Topics: Anticoagulants; Atrial Fibrillation; Chemical and Drug Induced Liver Injury; Female; Humans; Liver; Liver Failure; Liver Function Tests; Middle Aged; Phenprocoumon

Topics: Administration, Oral; Age Factors; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebral Hemorrhage; Cerebral Infarction; Clinical Trials as Topic; Contraindications; Fibrinolytic Agents; Humans; Male; Middle Aged; Phenprocoumon; Recurrence; Risk Factors

That tremor simulates atrial fibrillation and causes oral anticoagulation has not been reported. In a 69-year-old patient with diabetes, arterial hypertension and recurrent strokes, hand tremor developed since 1998. In September 2000 atrial fibrillation was diagnosed upon a routine and 24-hour ambulatory ECG. Because of the additional risk factors for stroke/embolism, phenprocoumon was begun. The diagnosis was changed to paroxysmal AF upon the following ECGs, showing sinus rhythm. Not earlier than 1 year after establishing the diagnosis,"atrial fibrillation" was identified as being due to a tremor artefact. Phenprocoumon was discontinued. Neurological investigations revealed Parkinson's disease as the cause of the tremor. Three weeks after initiation of pramipexol, the tremor artefact was no longer visible on ECG. Misinterpreting an ECG-artefact due to Parkinsons's tremor as atrial fibrillation may be followed by unnecessary diagnostic and therapeutic procedures, including long-term oral anticoagulation. Upon adequate treatment of Parkinson's disease, the tremor artefact immediately disappears from the ECG.

Topics: Aged; Anticoagulants; Antiparkinson Agents; Atrial Fibrillation; Benzothiazoles; Diagnosis, Differential; Diagnostic Errors; Electrocardiography; Female; Humans; Parkinson Disease; Phenprocoumon; Pramipexole; Thiazoles

Topics: Accidental Falls; Accidents, Traffic; Alcohol Drinking; Alcoholism; Anticoagulants; Atrial Fibrillation; Carotid Stenosis; Cerebral Hemorrhage; Contraindications; Craniocerebral Trauma; Heart Defects, Congenital; Humans; Phenprocoumon

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Cerebral Infarction; Dose-Response Relationship, Drug; Humans; Phenprocoumon; Platelet Aggregation Inhibitors; Recurrence; Risk Factors; Substance Withdrawal Syndrome

Topics: Age Factors; Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Chronic Disease; Heparin; Humans; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors

Deep vein thrombosis of the right leg occurred in a 77-year-old woman after percutaneous cardiac catheterization via the right femoral vein, performed to assess mitral valve disease with atrial fibrillation. She thereupon received intravenous heparin (1,000 IU/h; partial thromboplastin time 60-70s). 13 days later she developed a transient incomplete right brachiofacial hemiparesis with motor aphasia. Transthoracic echocardiography revealed a fresh left atrial thrombus. Platelet count fell from initially normal levels to 20 x 10(9)/l. Because type II heparin-associated thrombocytopenia was suspected heparin administration was discontinued and phenprocoumon administered. Heparin-dependent antibodies were demonstrated with the heparin-induced platelet activation test. Cross reactions occurred in vitro against all low-molecular heparins and heparinoid ORG 10172. The platelet count had become normal 17 days later, the leg veins had recanalized and the intraatrial thrombus had become much smaller. The patient declined cardiac surgery and was discharged on the 41st hospital day in satisfactory general condition on maintenance anticoagulant dosage.

Topics: Aged; Antibodies; Anticoagulants; Atrial Fibrillation; Cardiac Catheterization; Chondroitin Sulfates; Coronary Thrombosis; Dermatan Sulfate; Echocardiography; Female; Heparin; Heparinoids; Heparitin Sulfate; Humans; Mitral Valve Stenosis; Partial Thromboplastin Time; Phenprocoumon; Platelet Count; Thrombocytopenia; Thrombophlebitis

To investigate risk factors for embolization in patients with echocardiographically detected left atrial thrombi and to evaluate thrombus development, we examined 29 patients with transesophageal and transthoracic echocardiography at two points during a follow-up of 18 months. We compared patients with a history of possible arterial embolization (n = 13) with those without (n = 16) in regard to age, gender, left atrial dilatation, localization of the thrombus in the left atrial cavity, spontaneous echo contrast, and atrial fibrillation. Eight patients were treated with aspirin, 20 with phenprocoumon. Only left atrial spontaneous contrast was associated with thromboembolism (10/15 patients with spontaneous contrast experienced arterial embolism; p = 0.038). In six patients arterial embolism occurred after thrombus detection (14% per patient per year). Four of these patients were treated with phenprocoumon, two with aspirin. At reexamination, one thrombus was detected in the patient without anticoagulant treatment and one thrombus was detected in the 8 patients treated with aspirin (13%), compared with ten thrombi detected in the 20 patients (50%) treated with phenprocoumon (p = NS). In 17 patients no thrombus was seen at reexamination. Since only 2 patients had undergone thrombectomy and 3 experienced arterial embolism during follow-up, thrombi disappeared under medical therapy in 12 patients. Patients with left atrial thrombi have a high risk of arterial embolization despite proper anticoagulative or antiplatelet treatment. Embolization occurs significantly more often if spontaneous echo contrast can be visualized. Left atrial thrombi can be reduced in size by the administration of antiplatelet and anticoagulative agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aspirin; Atrial Fibrillation; Dilatation, Pathologic; Echocardiography; Echocardiography, Transesophageal; Embolism; Female; Follow-Up Studies; Heart Atria; Heart Diseases; Heparin; Humans; Intracranial Embolism and Thrombosis; Male; Middle Aged; Mitral Valve Stenosis; Peripheral Vascular Diseases; Phenprocoumon; Risk Factors; Thrombosis