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2.
BMC Nephrol ; 20(1): 114, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940121

RESUMO

BACKGROUND: Calciphylaxis is a life threatening complication in renal patients. Of great importance is the identification of concomitant factors for calciphylaxis. Due to the variability of clinical presentation the evaluation of such factors may be obscured when calciphylaxis diagnosis is based just on clinical features. We aimed to characterize associated factors only in patients with calciphylaxis proven by histomorphological parameters in addition to clinical presentation. METHODS: In a single center retrospective study we analyzed 15 patients in an 8 year period from 2008 to 2016. Only patients with clinical features and histomorphological proof of calciphylaxis were included. Criteria for histological diagnosis of calciphylaxis were intimal hyperplasia, micro thrombi or von Kossa stain positive media calcification. RESULTS: The mean age of patients was 64.8 years. Nine patients (60%) were female; 12 (80%) were obese with a Body-Mass-Index (BMI) > 30 kg/m2; 3 (20%) had no renal disease; 12 (80%) had CKD 4 or 5 and 10 (66.7%) had end-stage renal disease (ESRD). One-year mortality in the entire cohort was 73.3%. With respect to medication history, the majority of patients (n = 13 (86.7%)) received vitamin K antagonists (VKA); 10 (66.7%) were treated with vitamin D; 6 (40%) had oral calcium supplementation; 5 (33.3%) had been treated with corticosteroids; 12 (80%) were on proton pump inhibitors (PPI); 13 (86.7%) patients had a clinical proven hyperparathyroidism. Ten (66.7%) patients presented with hypoalbuminemia at diagnosis. CONCLUSIONS: The evaluation of biopsy proven calciphylaxis demonstrates that especially treatment with vitamin K antagonists and liver dysfunction are most important concomitant factors in development of calciphylaxis. As progression and development of calciphylaxis are chronic rather than acute processes, early use of DOACs instead of VKA might be beneficial and reduce the incidence of calciphylaxis.


Assuntos
Calciofilaxia , Falência Renal Crônica , Femprocumona/uso terapêutico , Trombose , Calcificação Vascular , Anticoagulantes/uso terapêutico , Biópsia/métodos , Calciofilaxia/epidemiologia , Calciofilaxia/etiologia , Calciofilaxia/patologia , Calciofilaxia/prevenção & controle , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Hepatopatias/epidemiologia , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Mortalidade , Seleção de Pacientes , Estudos Retrospectivos , Fatores de Risco , Trombose/etiologia , Trombose/patologia , Trombose/prevenção & controle , Calcificação Vascular/etiologia , Calcificação Vascular/patologia , Calcificação Vascular/prevenção & controle
3.
Thromb Haemost ; 119(6): 971-980, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30900223

RESUMO

Geriatric characteristics such as high age, multi-morbidity, polypharmacy and frailty are common in patients with atrial fibrillation (AF). In a retrospective study using a German claims database, effectiveness (ischaemic stroke/systemic embolism) and safety (intracerebral, gastrointestinal and major extracranial bleeding) were compared in patients with non-valvular AF starting non-vitamin K oral antagonists (NOACs) (apixaban, dabigatran and rivaroxaban) and phenprocoumon. Cox proportional hazards models were used to calculate adjusted hazard ratios, and interaction terms of the treatment group and geriatric status (defined by age ≥75 years, frailty, ≥ 4 co-morbidities and polypharmacy) were entered into the model. A total of 42,562 and 27,939 patients initiated NOAC and phenprocoumon treatment (mean age 74 years ± 11, 51% male) with a follow-up time of 147,785 person-years. Note that 52.9% of patients were elderly, 50.8% were frail, 37.0% were co-morbid and 46.5% had polypharmacy. NOAC use was not associated with effectiveness and gastrointestinal bleeding, neither in geriatric nor in non-geriatric patients. The hazard of major extracranial and intracranial bleeding was significantly decreased for NOAC use, with similar risk reduction in geriatric and non-geriatric patients: major extracranial bleeding 0.70 (95% confidence interval [CI], 0.56-0.87) to 0.73 (95% CI, 0.60-0.89) for the geriatric groups and 0.71 (95% CI, 0.56-0.93) to 0.76 (0.59-0.98) for the non-geriatric groups (p-values for interaction > 0.6); and intracranial bleeding 0.52 (95% CI, 0.39-0.69) to 0.59 (95% CI, 0.47-0.73) for the geriatric groups and 0.54 (95% CI, 0.37-0.79) to 0.65 (95% CI, 0.49-0.86) for the non-geriatric groups (p-values for interaction > 0.2). Hence, NOACs showed similar effectiveness and superior safety in geriatric and non-geriatric patients.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Femprocumona/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Dabigatrana/uso terapêutico , Feminino , Geriatria , Alemanha/epidemiologia , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Estudos Retrospectivos , Rivaroxabana/uso terapêutico , Vitamina K/metabolismo
4.
Pharmacoepidemiol Drug Saf ; 28(5): 616-624, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30828912

RESUMO

PURPOSE: Observational cohort studies are essential to evaluate the risk of adverse pregnancy outcomes associated with drug intake. Besides left truncation and competing events, it is crucial to account for the time-dynamic pattern of drug exposure. In fact, potentially harmful medications are often discontinued, which might affect the outcome. Ignoring these challenges may lead to biased estimation of drug-related risks highlighting the need for adequate statistical techniques. METHODS: We reanalyze updated data of a recently published study provided by the German Embryotox pharmacovigilance institute. The aim of the study was to quantify the effect of discontinuation of vitamin K antagonist phenprocoumon on the risk of spontaneous abortion. RESULTS: We outline multistate methodology as a powerful method removing bias in probability estimation inherent to commonly used crude proportions. We incorporate time-dependent discontinuation and competing pregnancy outcomes as separate states in a multistate model, which enables the formulation of hazard-based Cox proportional hazard models and the application of so-called landmark techniques. Results show that early discontinuation of phenprocoumon substantially reduces the risk of spontaneous abortion, which is of great importance for both pregnant women and treating physicians. CONCLUSIONS: An adequate handling of discontinuation times is essential when analyzing the risk of spontaneous abortion. The proposed concepts are not restricted to pregnancy outcome studies but have broad usage in other fields of epidemiology. Our nontechnical report may provide guidance for the design and analysis of future studies. Example code is provided.


Assuntos
Aborto Espontâneo , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Farmacovigilância , Femprocumona/administração & dosagem , Femprocumona/efeitos adversos , Aborto Espontâneo/induzido quimicamente , Aborto Espontâneo/epidemiologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Modelos Logísticos , Modelos Estatísticos , Gravidez , Medição de Risco
5.
J Thromb Thrombolysis ; 47(3): 384-391, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30729376

RESUMO

Patients taking oral anticoagulants (OACs) currently represent one-third of all patients treated for epistaxis and an upward trend is expected. New direct oral anticoagulants (DOACs) have been on the market for approximately 10 years. DOACs are favoured over Vitamin K-Antagonists (VKAs) in the current guidelines. There are barely studies that investigate the impact of DOACs on patients with epistaxis. A retrospective study was performed analysing all patients who had stationary treatment for epistaxis from 01.01.2011 to 01.01.2018 in a tertiary care centre. In a total of 466 patients, 46.1% were on OACs. The main indication was atrial fibrillation (AF, 67.4%).The number of DOACs taken surpassed that of the VKAs during the past 2 years. The length of hospital stay was significantly longer in the phenprocoumon group (3 ± 0.2 days) in comparison to both the rivaroxaban (2.3 ± 0.1) and the apixaban (2.2 ± 0.1) groups (p = 0.005). Posterior epistaxis occurred more frequently in the phenprocoumon group (10.8%) than in the rivaroxaban (0%) and apixaban (0%) groups (p = 0.03). A correlation between CHA2DS2-VASc score (risk score for apoplexy in patients with AF, p = 0.01), HAS-BLED score (score for assessment of major bleeding in patients taking anticoagulants with AF, p = 0.006), and length of hospital stay (p = 0.002) with recurrence of epistaxis was found. Shorter hospital stays and exclusively anterior bleeding was noted in AF patients taking rivaroxaban and apixaban, whereas AF patients taking phenprocoumon stayed in hospital longer and had more posterior bleeding.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Epistaxe/induzido quimicamente , Tempo de Internação , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Femprocumona/efeitos adversos , Femprocumona/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Estudos Retrospectivos , Medição de Risco/métodos , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico
7.
Int J Cancer ; 144(7): 1522-1529, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30246248

RESUMO

Use of vitamin K antagonists (VKAs) has been suggested to reduce the risk of prostate cancer. We conducted a nested case-control study using Danish demographic and health data registries and summarized existing evidence in a meta-analysis. The case-control study included all Danish men aged 40-85 years with incident histologically verified prostate adenocarcinoma between 2005 and 2015 (cases). For each case, we selected 10 age-matched controls. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CI) for prostate cancer associated with long-term VKA use adjusted for concomitant drug use, medical history and socioeconomic status. Among 38,832 prostate cancer cases, 1,089 (2.8%) had used VKAs for 3 or more years compared to 10,803 (2.8%) controls yielding a crude OR of 1.01 (95% CI, 0.95-1.08). Multivariable adjustment for covariates had limited influence on the association (OR, 1.03; 95% CI, 0.97-1.10). We observed no dose-response relationship (e.g. OR for 5-10 years of use, 1.06 95% CI, 0.97-1.16). We included 8 studies in the meta-analysis reporting effect estimates from 0.51 (95% CI, 0.23-1.13) to 1.10 (95% CI, 0.94-1.40). Using random effect methods, a pooled effect estimate of 0.86 (95% CI, 0.70-1.05) was obtained; however, there was considerable across-study heterogeneity (I2 : 93.9%). In conclusion, we did not observe a reduced risk of prostate cancer associated with VKA use in this nationwide study and, taken together with previous study findings, a major protective effect of VKAs against prostate cancer seems unlikely.


Assuntos
Neoplasias da Próstata/epidemiologia , Vitamina K/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Dinamarca/epidemiologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Femprocumona/administração & dosagem , Neoplasias da Próstata/prevenção & controle , Sistema de Registros , Varfarina/administração & dosagem
8.
Clin Oral Investig ; 23(5): 2273-2278, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30291493

RESUMO

OBJECTIVES: Bleeding after tooth extraction range from minor bleeding to life-threating haemorrhagic shock and are among the leading complications in patients under oral anticoagulation with direct oral anticoagulants (DOACs) or phenprocoumon. Little is known about how anticoagulation in patients under DOAC or phenprocoumon alters the characteristics, treatment or outcome of bleeding events, in comparison to non-anticoagulated patients. METHODS: Patients admitted to a tertiary ED in Bern, Switzerland, from June 1st 2012 to 31st May 2016 with bleeding related to tooth extraction under DOAC, phenprocoumon or without anticoagulation, were compared. RESULTS: Out of 161,458 emergency consultations, 64 patients with bleeding from tooth extraction were included in our study. In anticoagulation groups, we found significantly more delayed bleeding events than in patients without anticoagulation (9 (81.3%) DOAC, 19 (86.4%) phenprocoumon, 8 (30.8%) no anticoagulation, p < 0.001). Anticoagulated patients had to stay longer in the ED than non-anticoagulated patients, with no significant difference between DOAC or phenprocoumon (hours: 4.8 (3.2-7.6 IQR) DOAC, 3.0 (2.0-5.5 IQR) phenprocoumon, p = 0.133; 2.7 (1.6-4.6) no anticoagulation; p = 0.039). More patients with anticoagulation therapy needed surgery than patients without anticoagulant therapy (11 (68.8%) DOAC, 12 (54.6%) VKA, p = 0.506; 7(26.9%) no anticoagulation; p = 0.020). CONCLUSIONS: Delayed bleeding occur more often in anticoagulated patients with both DOAC and phenprocoumon compared to patients without anticoagulation. Bleeding events in anticoagulated patients with DOAC and phenprocoumon equally need longer ED treatment and more frequent surgical intervention. CLINICAL RELEVANCE: Caution with delayed bleeding in anticoagulated patients with DOACs and phenprocoumon is necessary and treatment of bleeding is resource-demanding.


Assuntos
Anticoagulantes/administração & dosagem , Hemorragia/etiologia , Femprocumona/administração & dosagem , Extração Dentária/efeitos adversos , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Suíça , Resultado do Tratamento , Adulto Jovem
9.
J Am Heart Assoc ; 7(17): e008650, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30371151

RESUMO

Background Preclinical data have indicated a link between use of vitamin K antagonists ( VKA ) and detrimental effects on vascular structure and function. The objective of the present study was to determine the relationship between VKA intake and different phenotypes of subclinical cardiovascular disease in the population. Methods and Results Clinical and laboratory data, as well as medical-technical examinations were assessed from 15 010 individuals aged 35 to 74 years during a highly standardized 5-hour visit at the study center of the population-based Gutenberg Health Study. In total, the study sample comprised 287 VKA users and 14 564 VKA nonusers. Multivariable analysis revealed an independent association between VKA intake and stiffness index (ß=+2.54 m/s; [0.41/4.66]; P=0.019), ankle-brachial index (ß=-0.03; [-0.04/-0.01]; P<0.0001), intima-media thickness (ß=+0.03 mm [0.01/0.05]; P=0.0098), left ventricular ejection fraction (ß=-4.02% [-4.70/-3.33]; P<0.0001), E/E' (ß=+0.04 [0.01/0.08]; P=0.014) left ventricular mass (ß=+5.34 g/m2.7 [4.26/6.44]; P<0.0001), and humoral markers of cardiac function and inflammation (midregional pro-atrial natriuretic peptide: ß=+0.58 pmol/L [0.50/0.65]; P<0.0001; midregional pro-adrenomedullin: ß=+0.18 nmol/L [0.14/0.22]; P<0.0001; N-terminal pro B-type natriuretic peptide: ß=+1.90 pg/mL [1.63/2.17]; P<0.0001; fibrinogen: ß=+143 mg/dL [132/153]; P<0.0001; C-reactive protein: ß=+0.31 mg/L [0.20/0.43]; P<0.0001). Sensitivity analysis in the subsample of participants with atrial fibrillation stratified by intake of VKA demonstrated consistent and robust results. Genetic variants in CYP 2C9, CYP 4F2, and VKORC 1 were modulating effects of VKA on subclinical markers of cardiovascular disease. Conclusions These data demonstrate negative effects of VKA on vascular and cardiac phenotypes of subclinical cardiovascular disease, indicating a possible influence on long-term disease development. These findings may be clinically relevant for the provision of individually tailored antithrombotic therapy.


Assuntos
Anticoagulantes/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Femprocumona/uso terapêutico , Volume Sistólico , Rigidez Vascular , Adrenomedulina/sangue , Adulto , Idoso , Índice Tornozelo-Braço , Doenças Assintomáticas , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fator Natriurético Atrial/sangue , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Espessura Intima-Media Carotídea , Feminino , Fibrinogênio/metabolismo , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Precursores de Proteínas/sangue , Embolia Pulmonar/tratamento farmacológico , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Trombose Venosa/tratamento farmacológico , Varfarina/uso terapêutico
10.
Thromb Haemost ; 118(11): 1930-1939, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30357779

RESUMO

Patients with heart failure (HF) are frequently anti-coagulated with vitamin K-antagonists (VKAs). The use of long-acting VKA may be preferable for HF patients due to higher stability of plasma concentrations. However, evidence on phenprocoumon-based oral anti-coagulation (OAC) therapy in HF is scarce. The aim of this study was to assess the impact of the presence of HF on quality of phenprocoumon-based OAC and the subsequent clinical outcome. Quality of OAC therapy and the incidence of adverse events were analysed in a cohort of regular care (n = 2,011) from the multi-centre thrombEVAL study program (NCT01809015) stratified by the presence of HF. To assess the modifiability of outcome, results were compared with data from individuals receiving specialized care for anti-coagulation (n = 760). Overall, the sample comprised of 813 individuals with HF and 1,160 subjects without HF in the regular care cohort. Quality of OAC assessed by time in therapeutic range (TTR) was 66.1% (47.8%/82.8%) for patients with HF and 70.6% (52.1%/85.9%) for those without HF (p = 0.0046). Stratification for New York Heart Classification (NYHA)-class demonstrated a lower TTR with higher NYHA classes: TTRNYHA-I 69.6% (49.4%/85.6%), TTRNYHA-II 66.5% (50.1%/82.9%) and TTRNYHA-≥III 61.8% (43.1%/79.9%). This translated into a worse net clinical benefit outcome for HF (hazard ratio [HR] 1.63 [1.31/2.02]; p < 0.0001) and an increased risk of bleeding (HR 1.40 [1.04/1.89]; p = 0.028). Management in a specialized coagulation service resulted in an improvement of all, TTR (∆+12.5% points), anti-coagulation-specific and non-specific outcome of HF individuals. In conclusion, HF is an independent risk factor for low quality of OAC therapy translating into an increased risk for adverse events, which can be mitigated by specialized care.


Assuntos
Anticoagulantes/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Insuficiência Cardíaca/tratamento farmacológico , Hemorragia/epidemiologia , Femprocumona/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Insuficiência Cardíaca/epidemiologia , Hemorragia/etiologia , Humanos , Incidência , Masculino , Femprocumona/efeitos adversos , Estudos Prospectivos , Risco , Resultado do Tratamento
11.
Pharmacogenomics ; 19(15): 1195-1202, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30207196

RESUMO

AIM: To study the effects of clinical and genetic factors on the phenprocoumon dose requirement in pediatric patients and to develop a dosing algorithm. METHODS: Pediatric patients who used phenprocoumon were invited to participate in a retrospective follow-up study. Clinical information and genotypes of genetic variations in CYP2C9, VKORC1, CYP4F2, CYP2C18 and CYP3A4 were collected and tested with linear regression for association with phenprocoumon dose requirement. RESULTS: Of the 41 patients included in the analysis, age, VKORC1, CYP2C9*2/*3 and CYP3A4*1B were statistically significantly associated with dose requirement, and together explained 80.4% of the variability in phenprocoumon dose requirement. CONCLUSION: Our study reveals that age and genetic variations explain a significant part of the variability in phenprocoumon dose requirement in pediatric patients.


Assuntos
Anticoagulantes/administração & dosagem , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP3A/genética , Femprocumona/administração & dosagem , Polimorfismo de Nucleotídeo Único/genética , Vitamina K Epóxido Redutases/genética , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Genótipo , Humanos , Lactente , Masculino , Farmacogenética/métodos , Estudos Retrospectivos
12.
BMJ Open ; 8(9): e022690, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30206088

RESUMO

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


Assuntos
Fibrilação Atrial , Hemorragia/prevenção & controle , Femprocumona , Pirazóis , Piridonas , Diálise Renal/métodos , Insuficiência Renal Crônica , Tromboembolia/prevenção & controle , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Feminino , Alemanha , Hemorragia/etiologia , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Femprocumona/administração & dosagem , Femprocumona/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Tromboembolia/etiologia
13.
BMC Fam Pract ; 19(1): 115, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-30021509

RESUMO

BACKGROUND: 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. METHODS: 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). RESULTS: 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 CHA2DS2-VASc-Score ≥ 2, indicating a need for oral anticoagulation (OAC). Prescription of OAC increased from 23.1% (n = 186) to 42.8% (n = 323, p < .01) with stable use of vitamin-k-antagonist (22.6-24.9%). NOAC increased from 0.6 to 19.2% (p < .01). Monotherapy with Acetylsalicylic acid (ASA) decreased from 15.3% (n = 123) to 8.2% (n = 62, p < .01). In group C (n = 1083), OAC increased from 35.3 to 55.4% (p < .01), with stable prescription rate of vitamin-k-antagonist (34.4-35.7%). NOAC increased from 0.9 to 21.5% (p < .01). CONCLUSIONS: 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.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/uso terapêutico , Femprocumona/uso terapêutico , Atenção Primária à Saúde , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/uso terapêutico , Fibrilação Atrial/complicações , Estudos Transversais , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Adulto Jovem
14.
Eur J Clin Pharmacol ; 74(10): 1317-1325, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29909576

RESUMO

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Femprocumona/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/prevenção & controle , Bases de Dados Factuais , Feminino , Seguimentos , Alemanha , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Femprocumona/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Vitamina K/antagonistas & inibidores , Adulto Jovem
16.
Clin Neurol Neurosurg ; 169: 116-120, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29655012

RESUMO

OBJECTIVES: The use of new anticoagulants potentially carries the risk of increased intracranial bleeding, but there is a lack of evidence. The aim of this study was to investigate whether the morbidity and mortality differs in head trauma patients depending on the type of anticoagulation. PATIENTS AND METHODS: A retrospective cohort study was conducted in 2009-2014. Based on sex, age, and Glasgow-Coma Scale (GCS), patients that received rivaroxaban were matched to two control groups, one that received no anticoagulant and another one that received phenprocoumon. The primary outcome was mortality. Among others, secondary outcome variables were the length of stay (LOS) at the hospital and presence of an intracranial injury. RESULTS: Sixty-nine patients (23 patients per group) were analyzed. The characteristics of patients did not differ significantly across groups. There were no significant differences between groups for the primary and secondary outcomes. Two patients died in the rivaroxaban group (one of them likely due to head trauma), while one patient died in the phenprocoumon group (likely not due to head trauma), and no patient died in the no anticoagulatoin group (p = 0.36). The LOS at the hospital was similar (5.0, 4.0, and 5.0 days; p = 0.94). An intracranial injury was observed in a similar number of patients in all groups (n = 11, n = 10, and n = 8; p = 0.75). CONCLUSION: Although limited in size, this study did not observe significant outcome differences in patients with traumatic head injuries, who received rivaroxaban, no anticoagulant or phenprocoumon. Although not significant, the only death likely due to head trauma in the study occurred in the rivaroxaban group. Larger studies are needed before clinical application of these findings.


Assuntos
Anticoagulantes/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/mortalidade , Inibidores do Fator Xa/uso terapêutico , Femprocumona/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Lesões Encefálicas Traumáticas/diagnóstico , Estudos de Coortes , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Masculino , Morbidade , Mortalidade/tendências , Femprocumona/efeitos adversos , Estudos Retrospectivos , Rivaroxabana/efeitos adversos
18.
Am J Cardiol ; 121(7): 879-887, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29402419

RESUMO

Vitamin K antagonist (VKA) is a commonly prescribed anticoagulant with a narrow therapeutic window. Genetic polymorphisms account for high VKA dosage variability. Hence, we performed an updated meta-analysis of all randomized clinical trials (RCTs) comparing genotype-guided VKA versus standard dosing algorithms. We conducted a systematic search of electronic databases from inception to October 2017 for all RCTs. The primary outcome was the percentage of time in therapeutic range (TTR). Secondary outcomes were international normalized ratio >4, major and all bleeding events, thromboembolism, adverse and serious adverse events, and all-cause mortality. We calculated the weighted mean difference for the primary outcome and risk ratio (RR) for secondary outcomes using a random-effect model. We included 20 RCTs and analyzed a total of 5,980 adult patients. Our pooled analysis showed greater improvement in TTR for the genotype-guided group in comparison with the standard group (mean difference 3.41%, 95% confidence interval [CI] 0.71 to 6.10, p = 0.01). In addition, there were significant reductions in major and all bleeding events ((RR 0.35, 95% CI 0.20 to 0.63, p = 0.0004) and (RR 0.79, 95% CI 0.66 to 0.95, p = 0.01), respectively). However, there were no significant differences between the groups for international normalized ratio >4 (RR 0.89, 95% CI 0.80 to 1.00, p = 0.06), thromboembolism (RR 0.81, 95% CI 0.56 to 1.17, p = 0.25), serious adverse events (RR 0.79, 95% CI 0.61 to 1.03, p = 0.08), any adverse events (RR 0.94, 95% CI 0.88 to 1.01, p = 0.07), or all-cause mortality (RR 0.73, 95% CI 0.32 to 1.66, p = 0.46). In conclusion, genotype-guided VKA dosing can improve the TTR and reduce the risk for bleeding episodes, in comparison with standard dosing algorithms.


Assuntos
Anticoagulantes/administração & dosagem , Genótipo , Testes Farmacogenômicos , Variantes Farmacogenômicos , Vitamina K/antagonistas & inibidores , Acenocumarol/administração & dosagem , Acenocumarol/efeitos adversos , Anticoagulantes/efeitos adversos , Causas de Morte , Hemorragia/induzido quimicamente , Humanos , Coeficiente Internacional Normatizado , Mortalidade , Razão de Chances , Femprocumona/administração & dosagem , Femprocumona/efeitos adversos , Tromboembolia/epidemiologia , Varfarina/administração & dosagem , Varfarina/efeitos adversos
19.
Clin Exp Med ; 18(3): 325-336, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29417256

RESUMO

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


Assuntos
Anticoagulantes/farmacologia , Fibrilação Atrial/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/fisiopatologia , Estudos de Casos e Controles , Dabigatrana/farmacologia , Inibidores do Fator Xa/farmacologia , Feminino , Tempo de Lise do Coágulo de Fibrina , Heparina de Baixo Peso Molecular/farmacologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Femprocumona/farmacologia , Plasma/efeitos dos fármacos , Plasma/metabolismo , Pirazóis/farmacologia , Piridonas/farmacologia , Rivaroxabana/farmacologia , Tromboplastina/farmacologia , Ativador de Plasminogênio Tecidual/farmacologia
20.
BMJ Case Rep ; 20182018 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-29440136

RESUMO

The cytochrome P450 is a superfamily of isoenzymes that are responsible for the metabolism of many drugs. Significant changes in pharmacokinetics and drug interactions may be due to induction of hepatic cytochrome P450 enzymes. Rifampicin is a common inducer of CYP3A4. We report a case of a 57-year-old woman who was suspected for endocarditis and therefore treated with rifampicin. Due to previous mechanical aortic valve replacement, she also received phenprocoumon for anticoagulation. Although continuing anticoagulant therapy, antibiotic coadministration led to normal international normalised ratio (INR) level. Fifteen days after the treatment with rifampicin ended, INR returned to therapeutic level.


Assuntos
Antibacterianos/uso terapêutico , Anticoagulantes/uso terapêutico , Insuficiência da Valva Aórtica/tratamento farmacológico , Endocardite/tratamento farmacológico , Implante de Prótese de Valva Cardíaca , Femprocumona/uso terapêutico , Rifampina/uso terapêutico , Antibacterianos/efeitos adversos , Anticoagulantes/efeitos adversos , Insuficiência da Valva Aórtica/cirurgia , Sistema Enzimático do Citocromo P-450 , Interações Medicamentosas , Feminino , Humanos , Coeficiente Internacional Normatizado , Pessoa de Meia-Idade , Femprocumona/efeitos adversos , Rifampina/efeitos adversos , Resultado do Tratamento , Vitamina K/antagonistas & inibidores
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