phenprocoumon and Brain-Ischemia

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

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

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

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

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

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; Aspirin; Brain Ischemia; Drug Therapy, Combination; Humans; Myocardial Infarction; Phenprocoumon; Platelet Aggregation Inhibitors; Ticlopidine