phenprocoumon and Stroke

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

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

For patients who suffered a TIA or a stroke the risk of a second event is high. The recurrence rate, however, can be significantly reduced by a number of prophylactic strategies. Methods for secondary stroke prevention include a healthy lifestyle, intensive body exercise, a low cholesterol diet, and the cessation of smoking. High levels of blood pressure, cholesterol and blood glucose should be rigorously controlled. In particular, blood pressure levels should remain below 135/85 mmHg including a physiological day/night profile. All patients at high risk for cardiac embolism should receive oral anticoagulants. As the risk for embolic events increases with age (especially in patients with atrial fibrillation), a rigid "age-cutoff" for anticoagulation is not justified.

Topics: Administration, Oral; Adult; Anticholesteremic Agents; Anticoagulants; Antihypertensive Agents; Blood Coagulation Disorders; Brain Ischemia; Carotid Artery, Internal; Carotid Stenosis; Cerebral Infarction; Clinical Trials as Topic; Contraceptives, Oral; Embolism; Endarterectomy, Carotid; Exercise; Female; Humans; Hypertension; Hypolipidemic Agents; Ischemic Attack, Transient; Life Style; Male; Phenprocoumon; Platelet Aggregation Inhibitors; Recurrence; Simvastatin; Smoking Cessation; Stroke

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

Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with cervical artery dissection, although some current guidelines-based on available evidence from mostly observational studies-suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection.. We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio [INR] 2·0-3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460.. Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% [95% CI -4 to 21], non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group.. Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection.. Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.

Topics: Acenocoumarol; Adult; Anticoagulants; Aspirin; Carotid Artery, Internal, Dissection; Denmark; Female; Germany; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Stroke; Switzerland; Vertebral Artery Dissection; Warfarin

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

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

Optimal antithrombotic/anticoagulation therapy in patients on chronic oral anticoagulation (OAC) undergoing drug-eluting stent (DES) implantation is unknown. We investigated the efficacy and safety of two regimens of antithrombotic/anticoagulation therapy in patients who present for DES implantation whilst on OAC.. We included a series of 515 patients on OAC who underwent DES implantation between 2002 and 2007. Based on predefined clinical and echocardiographic criteria, 306 patients continued OAC (triple therapy) and 209 patients discontinued OAC (dual therapy) for the time they received antiplatelet therapy with clopidogrel and aspirin [stent-related antithrombotic treatment (SRAT)]. The primary end point was a composite of death, myocardial infarction, stent thrombosis or stroke.. During SRAT the primary endpoint was observed in 13 patients in the group with triple therapy versus 15 patients in the group with dual therapy [Kaplan-Meier estimates 4.2% and 7.2%, odds ratio (OR) = 0.61, 95% confidence interval (CI) 0.29-1.28; P = 0.19]. At 2 years of follow-up, the primary endpoint was observed in 35 patients in the group with triple therapy versus 36 patients in the group with dual therapy (Kaplan-Meier estimates 14.1% and 18.0%, OR = 0.76, 95% CI: 0.48-1.21; P = 0.25). Two-year incidence of major bleeding was 1.4% (n = 4, triple therapy) versus 3.1% (n = 6, dual therapy) (P = 0.34).. In patients on chronic OAC undergoing DES implantation, clinical and echocardiographic criteria help to define postprocedural antithrombotic/anticoagulation therapy. Based on these criteria, both a double antiplatelet therapy (clopidogrel plus aspirin) and a triple therapy (OAC plus clopidogrel plus aspirin) are associated with favourable safety and efficacy.

Topics: Aged; Anticoagulants; Aspirin; Clopidogrel; Coronary Vessels; Drug Therapy, Combination; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Phenprocoumon; Platelet Aggregation Inhibitors; Postoperative Period; Prospective Studies; Stroke; Ticlopidine; Treatment Outcome

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

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

Here, the case of a 92-year-old female patient, who was diagnosed with atrial fibrillation and treated with phenprocoumon (Marcumar®), is reported. Pre-existing comorbidities were arterial hypertension, coronary heart disease, diabetes mellitus type 2, mild senile dementia and renal insufficiency. Despite treatment with phenprocoumon (Marcumar®), the patient experienced an ischaemic stroke. Her measured international normalized ratio (INR)-values during the months before the stroke were within the therapeutic range of 2-3, then suddenly decreased to 1.25. A retrospective inquiry failed to identify any significant changes in behaviour or therapy adherence, other than the consumption of 1.5 kg (3.3 lb) of hard-boiled candy liquorice in the days leading up to the stroke. The sudden decrease in INR-values may be explained by the influence of liquorice and its compounds on the pharmacokinetics of phenprocoumon (Marcumar®). In this context, the most important factors are the susceptibility of vitamin K antagonists to nutrition or metabolic irregularities, the influence of liquorice on the function of isoenzymes of the cytochrome P450 family that may lead to reduced bioavailability of phenprocoumon, and the influence of liquorice on peroxisome proliferator-activated receptor alpha transactivation.

Topics: Aged, 80 and over; Anticoagulants; Brain Ischemia; Female; Glycyrrhiza; Humans; International Normalized Ratio; Phenprocoumon; Retrospective Studies; Stroke

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

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

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

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

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

Reliable detection of anticoagulation status in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) is challenging but of importance especially in the emergency setting. This study evaluated the potential of a whole-blood clotting time assay based on Surface Acoustic Waves (SAW-CT) in stroke-patients. The SAW-technology was used for quick and homogenous recalcification of whole blood inducing a surface-activated clotting reaction quantified and visualised by real-time fluorescence microscopy with automatic imaging processing. In 20 stroke or transient ischaemic attack (TIA)-patients taking NOACs kinetics of SAW-CT were assessed and correlated to other coagulation parameters (PT, aPTT) and NOAC-plasma concentration measured by tandem mass spectrometry (LC-MS/MS). In 225 emergency patients with suspicion of acute stroke or TIA, SAW-CT values were assessed. Mean (± SD) SAW-CT in non-anticoagulated stroke patients (n=180) was 124 s (± 21). In patients on dabigatran or rivaroxaban, SAW-CT values were significantly higher 2 and 8 hours (h) after intake rising up to 267 seconds (s) (dabigatran, 2 h after intake) and 250 s (rivaroxaban, 8 h after intake). In patients on apixaban, SAW-CT values were only moderately increased 2 h after intake (SAW-CT 153 s). In emergency patients, SAW-CT values were significantly higher in NOAC and vitamin K antagonist (VKA)-treated as compared to non-anticoagulated patients. In conclusion, the SAW-CT assay is capable to monitor anticoagulant level and effect in patients receiving dabigatran, rivaroxaban and the VKA phenprocoumon. It has a limited sensitivity for apixaban-detection. If specific SAW-CT results were used as cut-offs, SAW-CT yields high diagnostic accuracy to exclude relevant rivaroxaban and dabigatran concentrations in stroke-patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Automation, Laboratory; Blood Coagulation; Chromatography, High Pressure Liquid; Dabigatran; Drug Monitoring; Female; Humans; Ischemic Attack, Transient; Male; Microfluidic Analytical Techniques; Microscopy, Fluorescence; Middle Aged; Phenprocoumon; Predictive Value of Tests; Pyrazoles; Pyridones; Reproducibility of Results; Rivaroxaban; Stroke; Tandem Mass Spectrometry; Time Factors; Treatment Outcome; Whole Blood Coagulation Time

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

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

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

For patients who survive intracerebral haemorrhage (ICH) during treatment with oral anticoagulation (OAC), the balance between the benefits and risks of restarting OAC is unclear. The decision to restart OAC or to start antiplatelet therapy in these patients therefore poses a dilemma for all physicians involved. We assessed the long-term outcome of patients who did or did not restart antithrombotic therapy after OAC-associated ICH.. We conducted a retrospective follow-up study of all patients discharged from our institution after OAC-associated ICH over a 10-year period. Data on the use of OAC or platelet inhibitors and the occurrence of vascular events during follow-up were assessed through questionnaires and patient files. The primary outcome was recurrent fatal or non-fatal stroke. Secondary outcomes were the occurrence of other haemorrhagic, thrombotic or thromboembolic events. With patients without antithrombotic treatment as reference, we calculated incidence ratios with corresponding 95% confidence intervals (CI) for treatment with OAC and for treatment with antiplatelet therapy.. We included 38 patients, of whom 21 (55%) died during a mean follow-up of 3.5 years. The medication regime changed frequently during follow-up, illustrated by the fact that two thirds of the patients who had resumed OAC within 2 months of ICH terminated this at later points in time. Two recurrent strokes occurred during 35.4 patient-years without antithrombotic medication, 7 during 63.8 patient-years on antiplatelet medication (incidence ratio 1.9; 95% CI, 0.4-9.4), and 3 during 19.5 patient-years on OAC (incidence ratio 2.7; 95% CI, 0.5-16.3). There was only 1 recurrent ICH, which occurred during treatment with OAC.. In this observational study, no significant difference in the primary outcome measure was found between the treatment groups, but there was a tendency towards a higher long-term risk of any stroke in patients who resumed OAC or started antiplatelet therapy. However, based on these results it is difficult to draw any concrete conclusions or make any strong recommendations. A randomized trial to assess the optimal long-term strategy after OAC-related ICH is warranted. Based on the point estimates of our study, such a trial should involve at least 300 patient-years of follow-up.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Cerebral Hemorrhage; Female; Fibrinolytic Agents; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Recurrence; Retrospective Studies; Risk Factors; Stroke; Surveys and Questionnaires; Survival Analysis; Thromboembolism; Treatment Outcome

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

Bleeding and thrombo-embolism are two of the most threatening adverse events associated with the use of continuous flow left ventricular assist devices (LVADs) in the treatment of severe heart failure. We analysed our LVAD patients treated with the HeartMate II (HM II) device by following a low anticoagulation regimen.. Between 2008 and February 2011, we implanted 40 HM II LVADs in our institution. Intention to treat was bridge to transplant in 25, destination therapy in 9, bridge to candidacy in 5 cases and bridge to recovery in 1 case. Heparin was started only after 24 h postoperatively, and Phenprocumon (Phen) was started after removal of all chest drains. International normalized ratio (INR) target in the years 2008-2009 was 2.5, and 2.0-2.5 since 2010. Acetyl salicylic acid (ASA) was prescribed 50-100 mg/day only in patients <55 years or in case of severe atherosclerotic disease of the right coronary artery. All data were analysed consecutively concerning thrombo-embolic and bleeding events.. Fifty-two percent of the patients were in INTERMACS level 1 or 2 at the time of implantation. The mean age was 58 ± 11 years, and the mean days under LVAD was 241 days (maximum: 1052 days). The survival rate was 87.5% after 30 years and 75% in the long term. Early postoperatively, no strokes or thrombo-embolic events occurred. In the long term, two patients suffered from ischaemic strokes, but recovered well. In both of these index events, the INR was lasting below 1.4. One of these two patients developed pump thrombosis additionally. Only three patients (ASA + Phen) developed gastrointestinal bleeding (7.5%). Two patients were withdrawn from Phen + ASA because of multiple angiodysplasia.. Compared with the literature, even a mild anticoagulation protocol does not increase the risk of thrombotic events, but reduces bleeding events in the use of an HM II LVAD.

Topics: Anticoagulants; Aspirin; Female; Heart Failure; Heart-Assist Devices; Heparin; Humans; Male; Middle Aged; Phenprocoumon; Stroke; Thromboembolism

Topics: Anticoagulants; Female; Heart Failure; Heart-Assist Devices; Humans; Male; Phenprocoumon; Stroke; Thromboembolism

The uncertain risk of secondary intracerebral hemorrhage (sICH) frequently keeps clinicians from initiating oral anticoagulation (OAC) early after ischemic cardioembolic stroke. The goal of this experimental study was to determine the risk of sICH depending on the timing of OAC initiation relative to stroke onset and to address the role of hematogenous macrophages for repair processes preventing OAC-associated sICH.. C57BL/6 mice were subjected to transient middle cerebral artery occlusion. Subgroups were treated with either the vitamin K antagonist (VKA) phenprocoumon or the direct thrombin inhibitor dabigatran etexilate. Hematogenous macrophages were depleted using intraperitoneal injections of clodronate-filled liposomes.. Time to therapeutic OAC was 48 hours with VKA and 0.5 hours with dabigatran etexilate treatment. In VKA-treated mice, the risk of sICH was high if effective OAC was already present at stroke onset or achieved within 48 hours after ischemia. With more delayed OAC, the risk of sICH rapidly decreased. Compared with VKA treatment, effective anticoagulation with dabigatran etexilate was associated with a significantly reduced extent of sICH, either if present at stroke onset or if achieved 48 hours later. Partial depletion of macrophages greatly increased the extent of OAC-associated sICH in the subacute stage of 3 to 4 days after ischemia.. Our findings suggest that repair mechanisms involving hematogenous macrophages rapidly decrease the risk of OAC-associated sICH in the first days after ischemic stroke. The lower risk of sICH under dabigatran etexilate compared with VKA treatment may facilitate early initiation of OAC after cardioembolic stroke.

Topics: Administration, Oral; Animals; Anticoagulants; Benzimidazoles; Blood Coagulation; Brain Ischemia; Cerebral Hemorrhage; Dabigatran; Disease Models, Animal; Intracranial Embolism; Macrophages; Male; Mice; Mice, Inbred C57BL; Phenprocoumon; Pyridines; Risk Factors; Stroke; Time Factors

Topics: Anticoagulants; Cerebral Infarction; Double-Blind Method; Humans; International Normalized Ratio; Morpholines; Multicenter Studies as Topic; Phenprocoumon; Randomized Controlled Trials as Topic; Rivaroxaban; Secondary Prevention; Stroke; Thiophenes

For many conditions causing transient ischemic attack or minor stroke, secondary prevention with early initiation of oral anticoagulation is indicated. The individual response to coumarins is known to vary widely and is not well predicted by clinical variables. Patients' discharge from hospital care is often delayed only because the therapeutic target range has not been reached yet. A feasible tool to guide coumarin dosing and thereby safely shortening time in hospital is required.. We established a polymerase chain reaction technique for rapid genotyping of the vitamin K epoxide reductase complex (VKORC1), which is the pharmaceutical target of the coumarins. C283 + 837C -> T (rs2359612) genotypes were determined in 49 patients who underwent de novo oral anticoagulation with phenprocoumon for cerebrovascular disease. Other variables potentially affecting phenprocoumon sensitivity were systematically evaluated.. Of 49 genotyped patients, 47 were treated in hospital until an international normalized ratio (INR) of 2-3 was reached. The time and the cumulative dose of phenprocoumon necessary to achieve the target INR both were strongly dependent on the individual C283 + 837C -> T genotype (Kruskal-Wallis test p = 0.0002, and p < 0.0001, respectively). Carriers of the TT genotype reached an INR of 2-3 after a mean time of 3.2 days (n = 5), CT carriers after 4.4 days (n = 27), and CC carriers after 6.5 days (n = 15). No other variable, including body weight, was significantly correlated with the treatment response.. In patients with cerebrovascular disease, genotyping for VKORC1 alone can strongly predict the individual response to de novo phenprocoumon treatment. The size of the pharmacogenetic test's potential effect on a more efficient use of hospital capacities remains to be shown by a controlled interventional study.

Topics: Aged; Anticoagulants; Female; Genotype; Humans; International Normalized Ratio; Male; Middle Aged; Mixed Function Oxygenases; Pharmacogenetics; Phenprocoumon; Precision Medicine; Stroke; Vitamin K Epoxide Reductases

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

Topics: Adult; Anticoagulants; Carotid Artery, Internal, Dissection; Fibrinolytic Agents; Heparin; Humans; Male; Phenprocoumon; Stroke; Tomography, X-Ray Computed; Ultrasonography, Doppler

Topics: Aged; Anticoagulants; Arrhythmias, Cardiac; Diagnosis, Differential; Dose-Response Relationship, Drug; Humans; Male; Mitral Valve Insufficiency; Paresis; Phenprocoumon; Risk Factors; Stroke

Coumarin anticoagulants are known to cause hepatotoxicity, but only a few cases have been reported. Coumarins are usually administered following cardiovascular surgery and the differential diagnosis is post-transfusion hepatitis.. We report the case of a 46-year-old woman who presented with jaundice, elevated liver function tests, positive antinuclear and smooth muscle antibodies following prodromal signs of fatigue and nausea. The patient had been treated with phenprocoumon for 5 months in order to prevent thromboembolism after two strokes assumed to be due to an open foramen ovale and an aneurysmatic atrial septum.. There was no evidence of viral or other causes of hepatitis. The patient rapidly developed subacute liver failure with encephalopathy and phenprocoumon treatment was stopped. With intensive care support, as well as high-dose prednisolone treatment, she recovered. Owing to positive antinuclear and smooth muscle antibodies, the initial diagnosis 'acute autoimmune hepatitis with liver failure was made.. The lack of hypergammaglobulinaemia and the rapid recurrence of hepatitis following re-exposure to phenprocoumon led to the final diagnosis of phenprocoumon-induced idiosyncratic drug allergic hepatitis with secondary autoimmune phenomena.

Topics: Anti-Inflammatory Agents; Anticoagulants; Biopsy; Chemical and Drug Induced Liver Injury; Diagnostic Errors; Drug Hypersensitivity; Female; Heart Aneurysm; Heart Septal Defects, Atrial; Hepatitis, Autoimmune; Humans; Liver Failure; Liver Function Tests; Middle Aged; Phenprocoumon; Prednisolone; Recurrence; Stroke; Thromboembolism; Time Factors

Physicians face a therapeutic dilemma in patients with acute hemorrhagic stroke requiring long-term, high-intensity anticoagulants because this treatment increases the risk of intracranial hemorrhage (ICH) 8- to 11-fold. We retrospectively studied 15 patients with ICH which occurred under anticoagulation with phenprocoumon, with an international norrmalized ratio (INR) of 2.5-6.5 on admission. Hemispheric, thalamic, cerebellar, intraventricular, or subarachnoid hemorrhage without aneurysm occurred. Absolute indications for anticoagulation were double, mitral, or aortic valve replacement, combined mitral valve failure with atrial fibrillation and atrial enlargement, internal carotid artery-jugular vein graft, frequently recurring deep vein thrombosis with risk of pulmonary embolism, and severe nontreatable ischemic heart disease. As soon as the diagnosis of ICH was established, INR normalization was attempted in all patients by administration of prothrombin complex, fresh frozen plasma, or vitamin K. After giving phenprocoumon antagonists (and neurosurgical therapy in four patients) heparin administration was started. Nine patients received full-dose intravenous and six low-dose subcutaneous heparin. The following observations were made: (a) All patients with effective, full-dose heparin treatment with a 1.5- to 2-fold elevation in partial thromboplastin time after normalization of the INR were discharged without complication. (b) Three of four of the patients with only incomplete correction of the INR (> 1.35) experienced relevant rebleeding within 3 days (all patients with an INR higher than 1.5), two of whom were on full-dose heparin. (c) Three of seven of the patients with normalized INR and without significant PTT elevation developed severe cerebral embolism. Although our data are based on a retrospective analysis, they support treatment with intravenous heparin (partial thromboplastin time 1.5-2 times baseline value) after normalization of the INR in patients with an ICH and an urgent need for anticoagulation.

Topics: Aged; Anticoagulants; Cardiovascular Diseases; Cerebral Hemorrhage; Female; Heparin; Humans; Male; Middle Aged; Partial Thromboplastin Time; Phenprocoumon; Retrospective Studies; Stroke; Venous Thrombosis