-
Preventive Medicine Reports Aug 2022In Germany, there is little real-world evidence on physicians' choice of oral anticoagulants (OACs). Our study aimed at assessing preferences for and prescribing...
In Germany, there is little real-world evidence on physicians' choice of oral anticoagulants (OACs). Our study aimed at assessing preferences for and prescribing patterns of treatment options for stroke prevention in atrial fibrillation in clinical practice in Germany. We conducted a nationwide quantitative online survey among office-based physicians in Germany. Physicians were asked about their preference for and use of treatment options as well as factors influencing their choice of a specific OAC. A total of n = 953 physicians was surveyed in September and October 2020 (general physicians: 36.0%; internists: 37.3%; cardiologists: 23.7%; neurologists: 10.5%; multiple specialties possible). Preference and use were highest for non-vitamin K oral anticoagulants (NOACs); followed by vitamin K antagonists (VKAs). Most preferred OACs were apixaban (39.3%), rivaroxaban (28.5%) and edoxaban (14.7%). Most used OACs were apixaban (24.3%), rivaroxaban (21.2%) and phenprocoumon (21.4%). NOACs were preferred more often than used (85.6% > 68.6%). VKAs were preferred less often than used (9.6% < 23.5%). OAC attributes and patient characteristics related to efficacy and safety, as well as patients' kidney function were most important when selecting a specific OAC. Federal and regional governance instruments likely influenced treatment decision-making. We found a high divergence between preferences for and use of available treatment options in clinical practice. Further exploration of the importance of OAC attributes, patient characteristics as well as federal and regional governance instruments for physicians' choice of a specific OAC may help to further optimize the healthcare of patients with atrial fibrillation in the long-term.
PubMed: 35757576
DOI: 10.1016/j.pmedr.2022.101861 -
Journal Der Deutschen Dermatologischen... Jul 2022We identified substantial heterogeneity in the perioperative management of antithrombotic drugs in skin surgery in Germany in 2012 and 2017 in two cross-sectional...
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.
Topics: Cross-Sectional Studies; Dermatologic Surgical Procedures; Dermatologists; Fibrinolytic Agents; Germany; Heparin; Humans; Phenprocoumon
PubMed: 35748181
DOI: 10.1111/ddg.14758 -
Journal of Cardiology Cases Jun 2022We report a multi-morbid patient with mechanical aortic valve and unstable and sub-therapeutic levels of international normalized ratio (INR), initially in phenprocoumon...
We report a multi-morbid patient with mechanical aortic valve and unstable and sub-therapeutic levels of international normalized ratio (INR), initially in phenprocoumon and later in warfarin therapy. All efforts, including self-testing using Point of Care Testing with telemedicine support to stabilize the patient's INR within the therapeutic range, were unsuccessful. Since INR fluctuations can occur due to poor or varied dietary vitamin K, 180 μg/day vitamin K was added to the patient's warfarin treatment in an attempt to stabilize INR fluctuations. Three weeks later INR was in therapeutic range and remained within range for two consecutive months suggesting beneficial effect of vitamin K. Our updated literature review demonstrates that vitamin K supplementation can improve the stability of INR without improvement of time therapeutic range. < Vitamin K antagonist (VKA) is the only approved anticoagulation therapy in patients with mechanical heart valves. The quality of anticoagulation therapy in some of these patients is challenged. There is insufficient evidence to advise routine vitamin K supplementation to all patients receiving VKA treatment. Supplementation, however, could be considered in patients with persistent INR instability, where no alternative anticoagulation therapy is available.>.
PubMed: 35685257
DOI: 10.1016/j.jccase.2021.12.011 -
Thrombosis Journal May 2022For stroke prevention in patients with atrial fibrillation (AF), direct oral anticoagulants (DOACs) have been increasingly prescribed instead of vitamin-K-antagonists...
BACKGROUND
For stroke prevention in patients with atrial fibrillation (AF), direct oral anticoagulants (DOACs) have been increasingly prescribed instead of vitamin-K-antagonists (VKA). For some patients a lower dosage of DOACs (ld-DOACs) is recommended. Ld-DOAC prescribing seems to be common, although previous studies did not show clear superiority of ld-DOACs over warfarin. In Germany, phenprocoumon is used almost exclusively as VKA. Randomized controlled trials comparing DOACs and phenprocoumon in the general population of patients with AF do not exist. Therefore, we aimed to compare ld-DOACs and phenprocoumon in a real-world setting in Germany.
METHODS
In a retrospective observational cohort study, claims data from a group of small to medium-sized health insurance companies were analysed. Risks for the outcomes thromboembolism, death and major bleeding were estimated by Cox regression. Out of 93,685 patients with atrial fibrillation and a first prescription of an oral anticoagulant, 20,179 receiving VKA and 21,724 ld-DOACs (29.6% of all DOAC patients) were included. For the sensitivity analysis phenprocoumon was compared to the five ld-DOAC groups (ld-apixaban, ld-dabigatran, ld-edoxaban, ld-rivaroxaban, and the composite of all ld-DOACs) after propensity-score matching.
RESULTS
Phenprocoumon was associated with statistically significant fewer thromboembolic events (HR = 1.29, 95% CI [1.13, 1.48], p < .001) and deaths (HR = 1.52, 95% CI [1.41, 1.63], p < .001) and a non-significant higher bleeding risk (HR = 0.89, 95% CI [0.79, 1.00], p = .051) than composite ld-DOAC. Regarding the subgroups, only patients with ld-apixaban had a statistically significant higher risk for thromboembolic events (HR = 1.42, 95% CI [1.21, 1.65], p < .001) and a lower bleeding risk (HR = 0.75, 95% CI [0.65, 0.86], p < .001). Ld-apixaban, ld-edoxaban, and ld-rivaroxaban were associated with a higher risk of death. The sensitivity analysis confirmed these associations.
CONCLUSION
Phenprocoumon seems to be superior to ld-DOACs for patients with AF. As a hypothesis phenprocoumon might turn out to be the wiser choice for high-risk patients with AF as compared to ld-DOACs, especially regarding thromboembolic events and death. Therefore, RCTs comparing ld-DOACs with phenprocoumon are needed.
PubMed: 35619140
DOI: 10.1186/s12959-022-00389-9 -
Deutsche Medizinische Wochenschrift... Apr 2022Non-vitamin-K dependent oral anti-coagulants (NOAC) are the current therapeutic standard for preventing strokes in patients with atrial fibrillation (AF) and should be...
Non-vitamin-K dependent oral anti-coagulants (NOAC) are the current therapeutic standard for preventing strokes in patients with atrial fibrillation (AF) and should be preferred over vitamin K antagonists (VKA) in this indication. This recommendation applies also to patients with VHF and concomitant chronic kidney disease (CKD). Real World Evidence (RWE), i. e., structured data from clinical practice, extends and confirms the clinical evidence generated in more formalized clinical trials with NOAC and VKA. In addition, RWE in respect to the indication showed that the superiority of NOAC versus the VKA warfarin can also be extrapolated to phenprocoumon, the commonly used VKA in Germany. Furthermore, data include evidence that the typical progression of CKD appears to be less pronounced in individuals treated with NOAC compared to those treated with VKA.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Renal Insufficiency, Chronic; Stroke; Vitamin K; Warfarin
PubMed: 35545071
DOI: 10.1055/a-1792-7094 -
Neurological Research and Practice May 2022The use of direct oral anticoagulants (DOAC) has increased sharply and DOAC are the oral anticoagulant therapy (OAT) of choice for the majority of patients with...
BACKGROUND AND PURPOSE
The use of direct oral anticoagulants (DOAC) has increased sharply and DOAC are the oral anticoagulant therapy (OAT) of choice for the majority of patients with newly-diagnosed atrial fibrillation. Intracranial hemorrhage is the most severe adverse event of OAT. Systematic data on the course of intracranial hemorrhage under DOAC compared to vitamin K antagonists (VKA) are warranted to enable shared decision making in AF patients needing OAT.
METHODS
This is a secondary analysis of the patients with intracranial bleedings from the prospective multicenter emergency department-based RADOA registry, which collected data on patients admitted with major bleeding while taking VKA or DOAC. The primary endpoint was in-hospital mortality until day 30. We evaluated hematoma volume and short-term clinical outcomes in relation to the extent of active OAT according to coagulation parameters and OAT plasma levels measured by UPLC-MS/MS.
RESULTS
Of 193 patients with major bleeding, 109 (56.5%) had intracranial hemorrhage [52.3% intracerebral (ICH), 33.9% subdural (SDH), 11.0% subarachnoidal (SAH)]. 64 (58.7%) were on VKA and 45 (41.2%) were on DOAC. On admission, we could confirm active anticoagulation in 97.7% of VKA-treated patients based on either INR > 1.3 or phenprocoumon levels and in 75.8% of DOAC-treated patients based on DOAC levels. Patients suffering an intracranial hemorrhage under VKA showed significantly larger hematoma volumes and a higher in-hospital mortality. Especially in intracerebral hemorrhage, we observed a higher initial severity and numerically greater proportion of early changes towards palliative therapy under VKA, which coincided with a numerically higher case fatality.
CONCLUSIONS
We show significantly smaller hematoma volumes for ICH and SDH under DOAC in comparison to VKA and a significantly lower 30-day in-hospital mortality rate of DOAC-ICH, even before the introduction of specific antidotes. These data strongly support the use of DOAC whenever possible in patients requiring OAT.
TRIAL REGISTRATION
http://www.
CLINICALTRIALS
gov ; Unique identifier: NCT01722786.
PubMed: 35491419
DOI: 10.1186/s42466-022-00183-y -
Pharmaceuticals (Basel, Switzerland) Apr 2022Growth differentiation factor (GDF)-15 inhibits platelet activation, prevents thrombus formation, and has been linked to bleeding events. This was a prospective study...
Growth differentiation factor (GDF)-15 inhibits platelet activation, prevents thrombus formation, and has been linked to bleeding events. This was a prospective study including 51 left-ventricular assist device (LVAD) patients on aspirin and phenprocoumon. Platelet surface expression of activated glycoprotein (GP) IIb/IIIa was assessed by flow cytometry, and platelet aggregation was measured by multiple electrode aggregometry (MEA) in response to arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor-activating peptide (TRAP), a protease-activated-receptor-1 (PAR-1) agonist. GDF-15 was determined with a commercially-available assay. There was a trend towards an inverse correlation of GDF-15 with activated GPIIb/IIIa in response to TRAP (r = -0.275, = 0.0532) but not in response to AA and ADP. Moreover, GDF-15 correlated with MEA TRAP (r = -0.326, = 0.0194), whereas it did not correlate with MEA ADP and MEA AA. In a second step, GDF-15 levels in the fourth quartile were defined as high GDF-15. Patients with high GDF-15 showed significantly lower TRAP-inducible platelet aggregation by MEA compared to patients in the first quartile (63 AU vs. 113 AU, = 0.0065). In conclusion, in LVAD patients receiving state-of-the-art antithrombotic therapy, GDF-15 correlates inversely with residual platelet reactivity via PAR-1.
PubMed: 35455481
DOI: 10.3390/ph15040484 -
Clinical Chemistry and Laboratory... Jun 2022Vitamin K and metabolites have a beneficial role in blood coagulation, bone metabolism and growth. However, the determination of vitamin K concentrations in the blood...
Development of a liquid chromatography mass spectrometry method for the determination of vitamin K1, menaquinone-4, menaquinone-7 and vitamin K1-2,3 epoxide in serum of individuals without vitamin K supplements.
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.
Topics: Chromatography, High Pressure Liquid; Chromatography, Liquid; Epoxy Compounds; Humans; Phenprocoumon; Tandem Mass Spectrometry; Vitamin K; Vitamin K 1; Vitamin K 2
PubMed: 35427444
DOI: 10.1515/cclm-2022-0192 -
Clinical Cardiology Jun 2022Atrial fibrillation is the most important risk factor for left atrial appendage (LAA) thrombi, a potentially life-threatening condition. Thrombus resolution may prevent... (Observational Study)
Observational Study
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.
Topics: Administration, Oral; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Echocardiography, Transesophageal; Humans; Phenprocoumon; Thrombosis
PubMed: 35373849
DOI: 10.1002/clc.23823 -
Clinical Cardiology Apr 2022Vitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long-term oral anticoagulant therapy (OAT) in patients with atrial... (Randomized Controlled Trial)
Randomized Controlled Trial
Influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism.
BACKGROUND
Vitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long-term oral anticoagulant therapy (OAT) in patients with atrial fibrillation or with pulmonary embolism. Due to interferences with matrix Gla-protein, an important vitamin K-dependent local calcification inhibitor in cardiovascular structures, VKA antagonists stimulate cardiovascular calcification (CVC). In contrast, rivaroxaban, a nonvitamin K-dependent oral anticoagulant (NOAC), should be neutral in terms of CVC. We seek to investigate these potential differences in CVC development between VKA versus NOACs in a randomized controlled trial (RCT).
METHODS
The influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism trial (NCT02066662) is a multicenter, prospective RCT with a two-arm, open-label study design. The primary endpoint is the progression of coronary and aortic valve calcification (quantified as calcification volume score) as assessed by cardiac computed tomography (CT) at 24 months in patients either treated by rivaroxaban or VKA. A total of 192 patients were randomized in a 1:1 fashion. The main inclusion criteria were the presence of atrial fibrillation and/or pulmonary embolism with the indication for OAT and pre-existent coronary calcification. The development of CVC will be assessed by follow-up CT at 12 and 24 months.
RESULTS
In total 192 patients (median age 70, 72% male) were enrolled over a period of 5 years and followed up for 2 years.
Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; Male; Pulmonary Embolism; Rivaroxaban; Stroke; Vitamin K
PubMed: 35332571
DOI: 10.1002/clc.23819