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1.
Europace ; 25(5)2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-37013704

RESUMO

AIMS: 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). METHODS AND RESULTS: 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)]. CONCLUSION: 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.


Assuntos
Fibrilação Atrial , Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Isquemia Encefálica/diagnóstico , Estudos de Casos e Controles , Anticoagulantes , Femprocumona/uso terapêutico , Fatores de Risco , Vitamina K , Administração Oral
2.
Transfusion ; 63 Suppl 3: S159-S167, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36971054

RESUMO

BACKGROUND: The military has used topical hemostatic agents to successfully treat life-threatening external bleeding for years. In contrast to the military environment, the general population are increasingly prescribed anticoagulants. There are only few comparative evaluations of topical hemostatic agents with anticoagulated human blood. It is important to understand the impact of these agents on those who take anticoagulants. STUDY DESIGN AND METHODS: Citrated blood of patients treated with enoxaparin, heparin, and acetylsalicylic acid, apixaban or phenprocoumon was incubated with different hemostatic agents (QuikClot Gauze, Celox Granules, Celox Gauze, Chito SAM 100, WoundClot Trauma Gauze, QuikClot Gauze Moulage Trainer and Kerlix) and rotational thromboelastometry was performed with non-activated thromboelastometry (NATEM reagent). RESULTS: All tested agents improved the onset of coagulation in all anticoagulants, mostly to a significant degree. Most significant improvements were produced by QuikClot Gauze and QuikClot Gauze Moulage Trainer, followed by the tested chitosans (Celox Granules, Celox Gauze, Chito SAM 100). Of the anticoagulant groups, the most significant improvements were seen in enoxaparin. This was followed in order by apixaban, heparin, and acetylsalicylic acid, and phenprocoumon. DISCUSSION: All the hemostatic agents tested were able to activate the clotting cascade earlier and initiate faster clot formation in anticoagulated blood. A definitive head-to-head comparison is not feasible, because of the limitations of an in-vitro analysis. However, the sometimes-presented hypothesis that kaolin-based hemostatic agents are ineffective in anticoagulated blood is inaccurate according to our data. Hemostasis with hemostatic agents appears most challenging with phenprocoumon.


Assuntos
Hemostáticos , Humanos , Hemostáticos/farmacologia , Femprocumona , Enoxaparina/farmacologia , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Heparina/farmacologia , Aspirina/farmacologia , Aspirina/uso terapêutico
3.
ASAIO J ; 69(6): 595-601, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36821448

RESUMO

VISUAL ABSTRACT: of key results. INR, international normalized ratio; TTR, time in therapeutic range; PTR, percentage of tests in range; HRAE, hemocompatibility-related adverse event; FFUV, first follow-up visit; GIB, gastrointestinal bleeding; HR, hazard ratio.http://links.lww.com/ASAIO/A961.


Assuntos
Coração Auxiliar , Varfarina , Humanos , Anticoagulantes/efeitos adversos , Coagulação Sanguínea , Coeficiente Internacional Normatizado/métodos , Femprocumona/efeitos adversos , Varfarina/efeitos adversos
4.
BMJ Open ; 13(1): e063490, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36593002

RESUMO

OBJECTIVES: 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. DESIGN: 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). SETTING: Data from a group of small-sized to medium-sized health insurance companies in Germany. PARTICIPANTS: 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). OUTCOME MEASURES: Outcomes were thromboembolic events, major bleeding and death during a 12-month follow-up period. RESULTS: 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. CONCLUSIONS: 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.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Femprocumona/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Varfarina/efeitos adversos , Rivaroxabana/efeitos adversos , Administração Oral , Anticoagulantes/efeitos adversos , Piridonas/uso terapêutico , Vitaminas/uso terapêutico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Estudos Retrospectivos
5.
Circulation ; 147(4): 296-309, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36335915

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: Thirty-nine sites randomized 97 patients (30% women; mean age 75 years; mean CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, female sex] score, 4.5; baseline characteristics balanced between groups): 48 to apixaban and 49 to VKA. The median follow-up time was 429 days (range, 37 to 1370) versus 506 days (range, 101 to 1379), respectively. Adherence to apixaban was >80% in 44 of 48 patients; the median time in therapeutic range on VKA was 50.7%. Composite primary safety outcome events occurred in 22 patients (45.8%) on apixaban and in 25 patients (51.0%) on VKA (hazard ratio, 0.93 [95% CI, 0.53-1.65]; Pnoninferiority=0.157). Composite primary efficacy outcome events occurred in 10 patients (20.8%) on apixaban and in 15 patients (30.6%) on VKA (P=0.51; log rank). There were no significant differences regarding individual outcomes (all-cause mortality, 18.8% versus 24.5%; major bleeding, 10.4% versus 12.2%; and myocardial infarction, 4.2% versus 6.1%, respectively). CONCLUSIONS: 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. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02933697.


Assuntos
Fibrilação Atrial , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Masculino , Femprocumona/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Estudos Prospectivos , Anticoagulantes/efeitos adversos , Acidente Vascular Cerebral/prevenção & controle , Hemorragia/induzido quimicamente , Piridonas/efeitos adversos , Diálise Renal/efeitos adversos , Infarto do Miocárdio/tratamento farmacológico , Resultado do Tratamento
6.
J Dtsch Dermatol Ges ; 20(7): 941-950, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35748181

RESUMO

BACKGROUND: We identified substantial heterogeneity in the perioperative management of antithrombotic drugs in skin surgery in Germany in 2012 and 2017 in two cross-sectional surveys. The first national guideline on this subject was published in 2014 and updated in 2021. We sought to identify whether the management of these drugs had changed. METHODS: We sent a paper-based survey to 1115 dermatologists throughout Germany asking them about their perioperative management of antithrombotic drugs in skin surgery, as well as their familiarity with the guideline. RESULTS: We received responses from 65 hospital- and 202 office-based dermatologists. Most dermatologists reported continuing antithrombotic drugs in their patients when performing minor surgeries. A notable proportion of dermatologists reported discontinuing phenprocoumon treatment perioperatively and bridging patients with heparin when performing more invasive surgeries. Continuation was less common during combination therapies. CONCLUSIONS: The proportion of physicians in Germany who reported managing antithrombotic drugs during skin surgery in ways that are in concordance with the national guideline has increased since 2012. However, continuing antithrombotic drugs during large excisions and sentinel lymph node biopsies, abstaining from bridging patients on phenprocoumon with heparin, and continuing antithrombotic combination therapies perioperatively need to be further encouraged, especially among office-based dermatologists.


Assuntos
Dermatologistas , Fibrinolíticos , Estudos Transversais , Procedimentos Cirúrgicos Dermatológicos , Fibrinolíticos/uso terapêutico , Alemanha , Heparina , Humanos , Femprocumona
7.
Cell Mol Life Sci ; 79(7): 387, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35763128

RESUMO

Ferroptosis, a type of iron-dependent programmed cell death distinct from apoptosis, necroptosis, and other types of cell death, is characterized by lipid peroxidation, reactive oxygen species production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury. Therefore, ferroptosis has become a major focus for translational research. However, despite its involvement in pathological conditions, there are no pharmacologic inhibitors of ferroptosis in clinical use. In the context of drug repurposing, a strategy for identifying new uses for approved drugs outside the original medical application, we discovered that vitamin K1 is an efficient inhibitor of ferroptosis. Our findings are strengthened by the fact that the vitamin K antagonist phenprocoumon significantly exacerbated ferroptotic cell death in vitro and also massively worsened the course of acute kidney injury in vivo, which is of utmost clinical importance. We therefore assign vitamin K1 a novel role in preventing ferroptotic cell death in acute tubular necrosis during acute kidney injury. Since the safety, tolerability, pharmacokinetics, and pharmacodynamics of vitamin K1 formulations are well documented, this drug is primed for clinical application, and provides a new strategy for pharmacological control of ferroptosis and diseases associated with this mode of cell death.


Assuntos
Injúria Renal Aguda , Ferroptose , Injúria Renal Aguda/tratamento farmacológico , Humanos , Ferro/metabolismo , Femprocumona , Vitamina K 1
8.
Clin Chem Lab Med ; 60(7): 1011-1019, 2022 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-35427444

RESUMO

OBJECTIVES: Vitamin K and metabolites have a beneficial role in blood coagulation, bone metabolism and growth. However, the determination of vitamin K concentrations in the blood in patients consuming a diet with naturally occurring vitamin K is currently challenging. We aim to develop a cost-effective and rapid method to measure vitamin K metabolites with potential application for clinics and research. METHODS: We developed a simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of vitamin K1, menaquinone-4 (MK-4), menaquinone-7 (MK-7) and vitamin K1-2,3 epoxide in human serum and validated the method in a study cohort of 162 patients tested for carbohydrate malabsorption and in 20 patients with oral phenprocoumon intake. RESULTS: The overall precision (CVs) ranged between 4.8 and 17.7% in the specified working range (0.06-9.0 nmol/L for all analytes except for MK-7 with 0.04-6.16 nmol/L). In the malabsorption cohort samples, measured values were obtained for all different vitamin K metabolites except for vitamin K1-2,3 epoxide. This metabolite could be detected only in patients with phenprocoumon intake. The good performance of the method is especially achieved by the interaction of three factors: the use of lipase in the sample preparation, the use of an atypical fluorinated reversed phase column, and a logarithmic methanol gradient. CONCLUSIONS: The described method is able to determine the concentration of four vitamin K metabolites in a time-efficient, simple and cost-effective manner. It can be suitable for both routine clinics and research.


Assuntos
Espectrometria de Massas em Tandem , Vitamina K 1 , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Compostos de Epóxi , Humanos , Femprocumona , Espectrometria de Massas em Tandem/métodos , Vitamina K , Vitamina K 2/análogos & derivados
9.
Clin Cardiol ; 45(6): 650-656, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35373849

RESUMO

BACKGROUND: 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. HYPOTHESIS: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Trombose , Administração Oral , Anticoagulantes/uso terapêutico , Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Ecocardiografia Transesofagiana , Humanos , Femprocumona/uso terapêutico , Trombose/etiologia , Trombose/prevenção & controle
10.
J Int Med Res ; 49(11): 3000605211049649, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34826377

RESUMO

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.


Assuntos
Isquemia Encefálica , Glycyrrhiza , Acidente Vascular Cerebral , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Feminino , Humanos , Coeficiente Internacional Normatizado , Femprocumona/efeitos adversos , Estudos Retrospectivos
11.
Ned Tijdschr Geneeskd ; 1652021 09 09.
Artigo em Holandês | MEDLINE | ID: mdl-34523845

RESUMO

Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.


Assuntos
Acenocumarol , Femprocumona , Acenocumarol/uso terapêutico , Anticoagulantes , Coagulação Sanguínea , Humanos , Coeficiente Internacional Normatizado , Femprocumona/farmacologia
12.
Eur J Med Res ; 26(1): 63, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187575

RESUMO

BACKGROUND: Bleeding is the most common complication of oral anticoagulants, due to inadequate dosing. CASE PRESENTATION: This report describes the clinical course of a patient who developed severe bleeding under therapy with phenprocoumon, despite an INR in the lower therapeutic range. Strikingly, aPTT was prolonged, while factor IX activity was significantly reduced. Acquired hemophilia was excluded, due to missing detection of inhibitors. Finally, sequencing part of the factor IX gene including nucleotide position c.110 revealed a hemizygous factor IX mutation c.110C > T p (Ala37Val). CONCLUSIONS: In rare cases, missense mutations in factor IX propeptide are associated with severe bleeding complications. The substitution of alanin at position 37 to either valin or threonin (Ala37Val or Ala37Thr) leads to hypersensitivity to vitamin k antagonists.


Assuntos
DNA/genética , Fator IX/genética , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Mutação , Femprocumona/efeitos adversos , Hemorragia Pós-Operatória/genética , Administração Oral , Anticoagulantes/efeitos adversos , Valva Aórtica/cirurgia , Análise Mutacional de DNA , Fator IX/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/metabolismo , Tomografia Computadorizada por Raios X
13.
Lancet Neurol ; 20(5): 341-350, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33765420

RESUMO

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.


Assuntos
Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Dissecação da Artéria Carótida Interna/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Dissecação da Artéria Vertebral/tratamento farmacológico , Acenocumarol/uso terapêutico , Adulto , Dissecação da Artéria Carótida Interna/complicações , Dissecação da Artéria Carótida Interna/diagnóstico por imagem , Dinamarca , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Femprocumona/uso terapêutico , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Suíça , Dissecação da Artéria Vertebral/complicações , Dissecação da Artéria Vertebral/diagnóstico por imagem , Varfarina/uso terapêutico
14.
J Nucl Med ; 62(1): 111-114, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32444372

RESUMO

Proinflammatory macrophages are important mediators of inflammation after myocardial infarction and of allograft injury after heart transplantation. The aim of this study was to image the recruitment of proinflammatory chemokine receptor 2-positive (CCR2+) cells in multiple heart injury models. Methods:64Cu-DOTA-extracellular loop 1 inverso (ECL1i) PET was used to image CCR2+ monocytes and macrophages in a heart transplantation mouse model. Flow cytometry was performed to characterize CCR2+ cells. Autoradiography on a human heart specimen was conducted to confirm binding specificity. 64Cu- and 68Ga-DOTA-ECL1i were compared in an ischemia-reperfusion injury mouse model. Results:64Cu-DOTA-ECL1i showed sensitive and specific detection of CCR2+ cells in all tested mouse models, with efficacy comparable to that of 68Ga-DOTA-ECL1i. Flow cytometry demonstrated specific expression of CCR2 on monocytes and macrophages. The tracer binds to human CCR2. Conclusion: This work establishes the utility of 64Cu-DOTA-ECL1i to image CCR2+ monocytes and macrophages in mouse models and provides the requisite preclinical information to translate the targeted clinical-grade CCR2 imaging probe for clinical investigation of heart diseases.


Assuntos
Traumatismos Cardíacos/diagnóstico por imagem , Traumatismos Cardíacos/metabolismo , Monócitos/metabolismo , Femprocumona/metabolismo , Tomografia por Emissão de Pósitrons , Receptores CCR2/metabolismo , Animais , Marcação por Isótopo , Camundongos , Camundongos Endogâmicos C57BL
15.
Thorac Cardiovasc Surg ; 69(6): 518-525, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33260235

RESUMO

BACKGROUND: The exact monitoring of the therapeutic-range international normalized ratio (INR) after left ventricular assist device (LVAD) implantation is an important aim to reduce the risk of thrombosis or bleeding complications. Service providers offer a telemedical anticoagulation service (CS). METHODS: We compared LVAD patients using the CS (n = 15) to those who received regular medical care (RMC; n = 15) to investigate if telemedicine supervision increased the INR-specific time in the therapeutic range (TTR) during anticoagulation. All patients received self-management training for phenprocoumon medication according to their INR value. INR values were documented for 12 months. A survey (scale: 1 = not satisfied and 10 = very satisfied) was used to determine patient's satisfaction and psychological well-being. RESULTS: A total of 1,798 INR measurements were analyzed. The TTRRosendaal was higher in patients undergoing RMC (78.1 ± 14.3%) compared with that in patients using the CS (58.3 ± 28.0%, p = 0.03). The patient's satisfaction with the coagulation setting at the beginning of the study (RMC: 6.7 ± 3.1, CS: 7.2 ± 3.0, p = 0.74) and psychological wellbeing (RMC: 6.5 ± 1.9, CS: 6.5 ± 2.7, p = 0.97) were comparable between both groups. CONCLUSION: We found that INR self-management is superior regarding the efficiency of post-LVAD anticoagulation therapy when compared with telemedical (CS)-based INR management in a small study cohort. Intensive training by experienced staff was able to replace CS.


Assuntos
Anticoagulantes/uso terapêutico , Monitoramento de Medicamentos , Insuficiência Cardíaca/terapia , Coração Auxiliar , Femprocumona/uso terapêutico , Implantação de Prótese/instrumentação , Autocuidado , Telemedicina , Trombose/prevenção & controle , Função Ventricular Esquerda , Anticoagulantes/efeitos adversos , Alemanha , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Hemorragia/induzido quimicamente , Humanos , Coeficiente Internacional Normatizado , Satisfação do Paciente , Femprocumona/efeitos adversos , Valor Preditivo dos Testes , Estudos Prospectivos , Implantação de Prótese/efeitos adversos , Qualidade de Vida , Trombose/diagnóstico , Trombose/etiologia , Resultado do Tratamento
16.
PLoS One ; 15(7): e0235639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649714

RESUMO

BACKGROUND: Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability to be maximally safe and effective. Switching from short-acting acenocoumarol to long-acting phenprocoumon could improve VKA control. AIMS: We assessed whether switching from acenocoumarol to phenprocoumon improves the time in the therapeutic range (TTR) and INR variability. METHODS AND RESULTS: In a retrospective cohort with data on 236,957 patients-years of VKA management from two first-line anticoagulation clinics in the Netherlands, we identified 124 patients in target range 2-3, 269 patients in target range 2-3.5 and 98 patients in target range 2.5-3.5 who switched from acenocoumarol to phenprocoumon. They were matched in a 1:2 ratio to non-switching controls using propensity score matching. Over the first 180 days after a switch, switchers' TTR declined 5 (95% CI 1 to 10), 10 (95% CI 7 to 13) and 5 (95% CI 0 to 11) percentage points relative to non-switchers, in target ranges 2-3, 2-3.5 and 2.5-3.5. Anticoagulation was more often supra-therapeutic in switchers, and switchers had a higher INR variability. In the following 180 days, TTR in switchers became 1 (95% CI -4 to 6), 4 (95% CI 0 to 7) and 6 (95% CI 1 to 12) percentage points better than in non-switchers. Switchers' INRs were much more stable than non-switchers'. CONCLUSION: Eventually, a switch from acenocoumarol to phenprocoumon leads to a higher TTR and a lower INR variability. However, this is preceded by a transition period with opposite effects. An improved conversion algorithm could possibly shorten the transition period. Until then, physicians and patients should decide whether switching is worth the increased risk during the transition phase.


Assuntos
Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Coeficiente Internacional Normatizado/métodos , Femprocumona/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Resultado do Tratamento , Tromboembolia Venosa/patologia , Vitamina K/antagonistas & inibidores
17.
Aliment Pharmacol Ther ; 52(2): 329-339, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32506456

RESUMO

BACKGROUND: To evaluate medical versus interventional treatment (transjugular thrombus fragmentation, local thrombolysis with or without stent implantation) in patients with acute non-cirrhotic, non-malignant portal vein thrombosis (PVT). METHODS: This prospective, observational study enrolled 65 patients with acute (<28 days since begin of symptoms, no cavernoma) PVT in nine centres. Thirty patients received medical treatment and 35 patients received interventional treatment. PVT was graded into grade 1: short thrombosis and incomplete occlusion of the vessel lumen and grade 2: extended thrombosis or complete occlusion. Treatment response was classified as partial or complete, if thrombosis was reduced by one grade or to <25% of the vessel diameter respectively. RESULTS: Partial and complete response rates were 7% and 30% in the medical compared to 17% and 54% (P < 0.001) in the interventional treatment group. In the multivariate analysis, interventional treatment showed a strong positive (OR 4.32, P < 0.016) and a myeloproliferative aetiology a negative (OR 0.09, P = 0.006) prediction of complete response. Complications were rare in the medical group and consisted of septicaemia and upper gastrointestinal bleeding of unknown origin in one patient each. Interventional treatment was accompanied by mild and self-limiting bleeding complications in nine patients, moderate intra-abdominal bleeding requiring transfusions (2 units) in one patient and peritoneal bleeding requiring surgical rescue in one patient. Four patients in each group developed intestinal gangrene requiring surgery. One patient died 52 days after unsuccessful interventional treatment. CONCLUSIONS: Compared to medical treatment alone, interventional treatment doubled response rates at the cost of increased bleeding complications.


Assuntos
Veia Porta/patologia , Derivação Portossistêmica Transjugular Intra-Hepática , Terapia Trombolítica , Trombose Venosa/terapia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Hepatopatias , Masculino , Pessoa de Meia-Idade , Femprocumona/uso terapêutico , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Estudos Prospectivos , Trombose Venosa/patologia , Adulto Jovem
18.
Graefes Arch Clin Exp Ophthalmol ; 258(5): 961-969, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31907644

RESUMO

PURPOSE: The goal of this study was to analyze the incidence of perioperative bleeding complications in rhegmatogenous retinal detachment. The handling of perioperative anticoagulation during vitreoretinal surgery remains controversial, since the risk of bleeding complications by its continuation has to be balanced against the risk of progression of retinal detachment and the risk of thromboembolic events when anticoagulation is interrupted. Nevertheless, only few studies have investigated the risk of perioperative bleeding complications in an emergency such as retinal detachment surgery. METHODS: We therefore examined the rate of all perioperative hemorrhages and separately the rate of only severe bleedings during vitrectomy, scleral buckling with or without drainage of subretinal fluid (SRD), or combined procedures due to retinal detachment in patients undergoing different types of perioperative anticoagulation including acetylsalicylic acetate (ASA), clopidogrel, heparin, low molecular weight heparin, and phenprocoumon. RESULTS: This retrospective single-center study included 893 patients with primary rhegmatogenous retinal detachment, n = 192 on anticoagulation and n = 701 serving as control without anticoagulation. Our analysis revealed no significantly increased rate of perioperative hemorrhages under anticoagulation with ASA 100 mg (all, 11.4%; severe, 5.0%) or phenprocoumon (all, 11.6%; severe, 2.3%) compared with controls (all, 13.0%; severe, 5.4%). However, frequencies of bleeding complications varied markedly regarding the type of surgical procedure: Scleral buckling plus SRD showed the highest rates of hemorrhages (all, 18.9%; severe, 9.1%) with significant difference (P < 0.001) compared with scleral buckling without SRD (all, 3.8%; severe, 0.6%) and vitrectomy (all, 9.2%; severe, 1.5%), respectively. Furthermore, subretinal bleeding was the most common type of perioperative hemorrhage. CONCLUSIONS: The data suggest not to stop ASA therapy prior to vitreoretinal surgery. Furthermore, we found no evidence of an increased risk for perioperative bleedings in patients under anticoagulation with vitamin-k antagonists with an INR within the sub-therapeutic range. SRD during scleral buckling procedure should be avoided as possible and regardless of any type of anticoagulation.


Assuntos
Complicações Intraoperatórias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Descolamento Retiniano/cirurgia , Hemorragia Retiniana/epidemiologia , Recurvamento da Esclera , Vitrectomia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Criança , Pré-Escolar , Clopidogrel/uso terapêutico , Drenagem , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Femprocumona/uso terapêutico , Tempo de Protrombina , Estudos Retrospectivos , Fatores de Risco , Líquido Sub-Retiniano
19.
Aging Clin Exp Res ; 32(3): 441-447, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31102254

RESUMO

BACKGROUND: Hospital admissions resulting from traumatic intracranial haemorrhages (TIH) in older people are increasing. There are concerns regarding an increased risk of a TIH in people taking oral anticoagulants (OAC) like phenprocoumon. AIMS: The aim of this study was to estimate the incremental risk of a TIH associated with OAC in older people. Furthermore, this study explored differences in risk according to functional status. METHODS: The study took data from a large German health insurance provider and combined hospital diagnoses with data regarding drug dispensing to estimate rates of a TIH in people with and without exposure to phenprocoumon. Analyses were stratified by sex and by severe functional impairment as disclosed by the long-term care insurance provider. RESULTS: Overall, exposure to OAC resulted in 2.7 times higher rates of TIH. People with severe functional impairment had a higher baseline risk of TIH than people without severe functional impairment. However, the incremental risk in those exposed to OAC was similar among people with and without severe functional impairment (standardised incidence rate difference 15.73 (95% CI 7.84; 23.61) and 12.10 (95% CI 9.63; 14.57) per 10,000 person-years, respectively). CONCLUSIONS: OAC increases the risk of TIH considerably. The incremental risk of TIH in those exposed to OAC is comparable between people with and without severe functional impairment. The presence of severe functional impairment per se should not exclude such patients from the potential benefits of OAC. For now, the prescription should be personalized based on individual fall risk factors and risk-taking behaviour.


Assuntos
Acidentes por Quedas , Anticoagulantes/efeitos adversos , Hemorragia Intracraniana Traumática/epidemiologia , Femprocumona/efeitos adversos , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Estudos de Casos e Controles , Feminino , Humanos , Hemorragia Intracraniana Traumática/etiologia , Masculino , Pessoa de Meia-Idade , Femprocumona/administração & dosagem , Desempenho Físico Funcional , Medição de Risco
20.
Neurocrit Care ; 33(1): 105-114, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31659679

RESUMO

BACKGROUND: Demographic changes are leading to an aging society with a growing number of patients relying on anticoagulation, and vitamin K antagonists (VKA) are still widely used. As mortality and functional outcomes are worse in case of VKA-associated hemorrhagic stroke, phenprocoumon treatment seems to be a negative prognostic factor in case of subarachnoid hemorrhage (SAH). The purpose of this study was to analyze whether phenprocoumon treatment does worsen the outcome after non-traumatic SAH. METHODS: All patients treated for non-traumatic SAH between January 2007 and December 2016 in our institution were retrospectively analyzed. After exclusion of patients with anticoagulant or antiplatelet treatment other than phenprocoumon, we analyzed 1040 patients. Thirty-three patients (3%) of those were treated with continuous phenprocoumon. In total, 132 out of all 1007 patients without anticoagulant treatment of the remaining patients were matched as control group (ratio = 1:4). RESULTS: Patients with phenprocoumon treatment were significantly older (66.5 years vs. 53.9 years; p < .0001), and admission status was significantly more often poor (66.7% vs. 41.8%, p = .007) compared to all patients without anticoagulant treatment. Further, bleeding pattern and rates of early hydrocephalus did not differ. Matched-pair analysis revealed a significant higher rate of angio-negative SAH in the study group (p = .001). Overall rates of hemorrhagic or thromboembolic complications did not differ (21.4% vs. 18.8%; NS) but were more often fatal, and 30-day mortality rate was significantly higher in the phenprocoumon group than in patients of the matched-pair control group (33% vs. 24%; p < .001). 30% of the phenprocoumon group and 37% of the matched-pair control group reached favorable outcome. However, poor outcome was strong associated with the reason for phenprocoumon treatment. CONCLUSION: Patients with phenprocoumon treatment at the time of SAH are significantly older, admission status is worse, and 30-day mortality rates are significantly higher compared to patients without anticoagulant treatment. However, outcome at 6 months did not differ to the matched-pair control group but seems to be strongly associated with the underlying cardiovascular disease. Treatment of these patients is challenging and should be performed on an interdisciplinary base in each individual case. Careful decision-making regarding discontinuation and bridging of anticoagulation and close observation is mandatory.


Assuntos
Anticoagulantes/uso terapêutico , Estado Funcional , Mortalidade , Femprocumona/uso terapêutico , Hemorragia Subaracnóidea/fisiopatologia , Adulto , Idoso , Aneurisma Roto/complicações , Aneurisma Roto/diagnóstico por imagem , Angiografia Digital , Angiografia Cerebral , Feminino , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Ruptura Espontânea , Índice de Gravidade de Doença , Hemorragia Subaracnóidea/etiologia , Vasoespasmo Intracraniano/epidemiologia
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