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Thrombosis Journal Nov 2022Patients with end-stage kidney disease on haemodialysis suffer from frequent complications requiring hospitalisation. Atrial fibrillation is a burdensome comorbidity...
Atrial fibrillation and anticoagulation are associated with hospitalisations in patients with end-stage kidney disease on haemodialysis: a prospective population-based cohort study.
BACKGROUND
Patients with end-stage kidney disease on haemodialysis suffer from frequent complications requiring hospitalisation. Atrial fibrillation is a burdensome comorbidity amongst patients on haemodialysis. We aimed to assess frequency, reasons, and duration of hospitalisations in haemodialysis patients and their association with atrial fibrillation and anticoagulation.
METHODS
Prevalent patients with end-stage kidney disease on haemodialysis were recruited into a prospective cohort study and observed for a median observation time of 3.4 years. Hospitalisations were recorded from discharge letters, medical records, and patient interviews. The association of atrial fibrillation, anticoagulation, and time-in-therapeutic range of vitamin K antagonist treatment with hospitalisations was analysed using negative binomial regression.
RESULTS
Out of 625 patients, 238 (38.1%) had atrial fibrillation. Median number of hospitalisations per patient was 3.0 (1.0-5.0). Incidence rate of hospitalisation was 1.7 per patient-year in all and 1.9 in atrial fibrillation patients, median duration per hospitalisation was 7.9 (4.8-12.9) and 8.8 (5.7-13.3) days, respectively. Most frequent reasons for hospitalisation were vascular access complication/intervention (11.7%) and infection/fever (11.4%), while bleeding events comprised 6.0% of all hospitalisations. Atrial fibrillation patients had 27% higher risk of hospitalisation than patients without atrial fibrillation (incidence rate ratio [IRR] 1.27, 95% confidence interval [CI] 1.10-1.47). In atrial fibrillation patients, anticoagulation (enoxaparin or phenprocoumon, 41.6% of AF patients) was associated with increased risk of all-cause (IRR 1.38, 95%CI 1.14-1.69) and bleeding-related hospitalisation (IRR 1.96, 95%CI 1.06-3.63). There was no association between anticoagulation and stroke-related hospitalisation. In atrial fibrillation patients on phenprocoumon, increasing time-in-therapeutic range was associated with decreased risk of all-cause (IRR 0.35, 95%CI 0.14-0.87), but not bleeding-related hospitalisation (IRR 0.13, 95%CI 0.01-1.38).
CONCLUSION
In haemodialysis patients, presence of atrial fibrillation and, among those with atrial fibrillation, anticoagulation were associated with higher risk of all-cause hospitalisation, including bleeding-related hospitalisation in the latter. Increasing time-in-therapeutic range in patients on vitamin K antagonist treatment was associated with decreased risk of all-cause, but not bleeding-related hospitalisation.
PubMed: 36451221
DOI: 10.1186/s12959-022-00434-7 -
Pharmaceuticals (Basel, Switzerland) Nov 2022Background: Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not...
Pharmacokinetics of Phenprocoumon in Emergency Situations-Results of the Prospective Observational RADOA-Registry (Reversal Agent Use in Patients Treated with Direct Oral Anticoagulants or Vitamin K Antagonists Registry).
Background: Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not been analyzed in emergency situations. Methods: Phenprocoumon-treated patients with major bleeding or urgent surgery were included in a prospective, observational registry. Phenprocoumon drug concentrations were analyzed in samples, collected as part of routine care using ultraperformance liquid chromatography tandem mass spectrometry. Moreover, anticoagulant intensity and drug half-life (t1/2) were calculated. Results: 115 patients were included. Phenprocoumon levels declined over time with a half-life of 5.27 and 5.29 days in patients with major bleedings (n = 82) and with urgent surgery (n = 33). Baseline phenprocoumon levels were 2.2 times higher in the bleeding group compared to the surgery group (1.92 vs. 0.87 ng/mL, p < 0.0001). International normalized ratio (INR) values decreased rapidly during the first 24 h. In 27.6% of patients a rebound of INR (recurrent increase > 1.5) was observed which was associated with significantly increased bleeding rates (22% vs. 4.2% in patients with or without INR rebound, p = 0.012). Conclusions: In emergency situations, the long half-life of phenprocoumon may cause INR rebound and associated recurrent bleedings. Optimal management may need to include repeated vitamin K supplementation over days.
PubMed: 36422567
DOI: 10.3390/ph15111437 -
Circulation Jan 2023Non-vitamin K oral anticoagulants have become the standard therapy for preventing stroke and ischemic thromboembolism in most patients with atrial fibrillation (AF). The... (Randomized Controlled Trial)
Randomized Controlled Trial
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 CHADS-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]; =0.157). Composite primary efficacy outcome events occurred in 10 patients (20.8%) on apixaban and in 15 patients (30.6%) on VKA (=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.
Topics: Humans; Female; Aged; Male; Phenprocoumon; Atrial Fibrillation; Prospective Studies; Anticoagulants; Stroke; Hemorrhage; Pyridones; Renal Dialysis; Myocardial Infarction; Treatment Outcome
PubMed: 36335915
DOI: 10.1161/CIRCULATIONAHA.122.062779 -
Saudi Journal of Biological Sciences Dec 2022COVID-19 is a progressing pandemic of coronavirus disease-2019, which had drowned the whole world in a deep sorrow sea. Uncountable deaths were extending the list of...
COVID-19 is a progressing pandemic of coronavirus disease-2019, which had drowned the whole world in a deep sorrow sea. Uncountable deaths were extending the list of deaths every single day. The present research was aimed to study the multi-target interaction of coumarins against COVID-19 using molecular docking analysis. The structure of coumarin compounds was checked for ADME and Lipinski rule of five by using SwissADME, an online tool. SARS-CoV-2 proteins such as RdRp, PLpro, Mpro and spike protein were collected from the Protein Data Bank. The molecular docking study was performed in the PyRx tool, and the molecular interactions were visualised by Discovery Studio Visualizer. All the coumarin compounds used in the study were obeyed Lipinski's rule of 5 without any violations. All the three designed derivatives of phenprocoumon, hymecromone, and psoralen were showed high binding affinity and prominent interactions with the drug target. The presence of -OH groups in the compound, His41, a catalytic dyad in Mpro, number of and the distance of hydrogen bond interactions with SARS-CoV-2 targets was accountable for the high binding attractions. The modified drug structures possess better binding efficacy towards at least three targets compared to their parent compounds. Further, molecular dynamic studies can be suggested to find the ligand-protein complex stability. The present study outcome reveals that the designed coumarins can be synthesised and examined as a potent inhibitory drug of SARS-CoV-2.
PubMed: 36187455
DOI: 10.1016/j.sjbs.2022.103458 -
The American Journal of Case Reports Sep 2022BACKGROUND Despite use of optimal oral anticoagulation regimens, left atrial appendage (LAA) thrombus may develop and persist in patients with atrial fibrillation (AF)....
Percutaneous Left Atrial Appendage Closure with the LAmbre Device Protected by a Cerebral Protection System in a 76-Year-Old Man with Persistent Left Atrial Appendage Thrombus.
BACKGROUND Despite use of optimal oral anticoagulation regimens, left atrial appendage (LAA) thrombus may develop and persist in patients with atrial fibrillation (AF). The therapeutic options in this population are limited. Percutaneous LAA closure (LAAC) is performed to reduce thrombus formation and the risk of thromboembolism. However, this approach is prohibited in patients with LAA thrombus. We report the case of a 76-year-old man with AF and persistent LAA thrombus who underwent percutaneous LAAC with the LAmbre device protected by the SENTINEL Cerebral Protection System (CPS). CASE REPORT A 76-year-old man with history of persistent AF treated with pulmonary veins and LAA isolation developed LAA thrombus resistant to different anticoagulation therapies, including apixaban and Phenprocoumon, with a target international normalized ratio (INR) of 3-3,5. Repeated follow-up transesophageal echocardiography showed a persistent LAA thrombus despite optimal INR values. Thus, we performed a percutaneous LAAC using a double-umbrella-designed appendage occluder and a CPS to minimize the risk of intraprocedural cerebral embolization. The procedure was guided by transesophageal echocardiography and fluoroscopy. No signs of systemic thromboembolism were noted, and the CPS filters showed no evidence of thrombotic material. CONCLUSIONS This report shows that the use of a CPS during percutaneous LAAC may reduce the risk of procedural cerebral embolization and could be used as an alternative therapy for patients with contraindication or lack of effectiveness of oral anticoagulation.
Topics: Aged; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Catheterization; Heart Diseases; Humans; Male; Thromboembolism; Thrombosis; Treatment Outcome
PubMed: 36101478
DOI: 10.12659/AJCR.937063 -
Clinical Research in Cardiology :... Jun 2023The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is a worldwide non-interventional study of stroke prevention in patients with...
GARFIELD-AF: risk profiles, treatment patterns and 2-year outcomes in patients with atrial fibrillation in Germany, Austria and Switzerland (DACH) compared to 32 countries in other regions worldwide.
BACKGROUND
The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is a worldwide non-interventional study of stroke prevention in patients with non-valvular AF.
METHODS AND RESULTS
52,080 patients with newly diagnosed AF were prospectively enrolled from 2010 to 2016. 4121 (7.9%) of these patients were recruited in DACH [Germany (n = 3567), Austria (n = 465) and Switzerland (n = 89) combined], and 47,959 patients were from 32 countries in other regions worldwide (ORW). Hypertension was most prevalent in DACH and ORW (85.3% and 75.6%, respectively). Diabetes, hypercholesterolaemia, carotid occlusive disease and vascular disease were more prevalent in DACH patients vs ORW (27.6%, 49.4%, 5.8% and 29.0% vs 21.7%, 40.9%, 2.8% and 24.5%). The use of non-vitamin K antagonist oral anticoagulants (NOACs) increased more in DACH over time. Management of vitamin K antagonists was suboptimal in DACH and ORW (time in therapeutic range of INR ≥ 65% in 44.6% and 44.4% of patients or ≥ 70% in 36.9% and 36.0% of patients, respectively). Adjusted rates of cardiovascular mortality and MI/ACS were higher in DACH while non-haemorrhagic stroke/systemic embolism was lower after 2-year follow-up.
CONCLUSIONS
Similarities and dissimilarities in AF management and clinical outcomes are seen in DACH and ORW. The increased use of NOAC was associated with a mismatch of risk-adapted anticoagulation (over-and-undertreatment) in DACH. Suboptimal control of INR requires educational activities in both regional groups. Higher rates of cardiovascular death in DACH may reflect the higher risk profile of these patients and lower rates of non-haemorrhagic stroke could be associated with increased NOAC use.
Topics: Humans; Anticoagulants; Atrial Fibrillation; Austria; Switzerland; Administration, Oral; Stroke; Registries; Risk Factors
PubMed: 36094573
DOI: 10.1007/s00392-022-02079-y -
JACC. Case Reports Aug 2022Direct oral anticoagulant agents (DOACs) are widely used in the treatment of arterial and venous thrombi. We report the case of a 32-year-old patient who was receiving...
Direct oral anticoagulant agents (DOACs) are widely used in the treatment of arterial and venous thrombi. We report the case of a 32-year-old patient who was receiving permanent DOAC therapy. Despite adequate use, 2 large left ventricular thrombi developed. Surgical thrombectomy was performed. The patient recovered well and received anticoagulation with phenprocoumon thereafter. ( ).
PubMed: 36062055
DOI: 10.1016/j.jaccas.2022.05.033 -
Journal Der Deutschen Dermatologischen... Jul 2022Hintergrund und Zielsetzung: Wir haben in zwei Querschnittsumfragen in den Jahren 2012 und 2017 eine erhebliche Heterogenität im perioperativen Management von...
Hintergrund und Zielsetzung: Wir haben in zwei Querschnittsumfragen in den Jahren 2012 und 2017 eine erhebliche Heterogenität im perioperativen Management von Antithrombotika unter Dermatologen in Deutschland festgestellt. Die erste deutsche Leitlinie zu diesem Thema wurde 2014 veröffentlicht und im Jahr 2021 aktualisiert. Wir wollten herausfinden, wie sich der Umgang mit Antithrombotika verändert hat. Methodik: Wir haben eine papierbasierte Umfrage an 1115 Dermatologen in ganz Deutschland versandt und sie zu ihrem perioperativen Management von Antithrombotika bei Operationen an der Haut sowie zu ihrer Vertrautheit mit der Leitlinie befragt. Ergebnisse: Wir erhielten Antworten von 65 stationär tätigen und 202 niedergelassenen Dermatologen. Die meisten Dermatologen gaben an, Antithrombotika bei kleineren Operationen fortzuführen. Ein nennenswerter Anteil der Dermatologen gab an, bei invasiveren Operationen die Behandlung mit Phenprocoumon perioperativ zu pausieren und mit Heparin zu überbrücken. Bei Kombinationstherapien war das Fortführen der Behandlung weniger verbreitet. Schlussfolgerungen: Der Anteil der Dermatologen in Deutschland, die angaben, Antithrombotika bei Operationen an der Haut leitlinienkonform zu managen, ist seit 2012 gestiegen. Das Fortführen von Antithrombotika bei großen Exzisionen und Wächterlymphknotenexstirpationen, der Verzicht auf die Überbrückung von Phenprocoumon mit Heparin und das perioperative Fortführen antithrombotischer Kombinationstherapien müssen jedoch weiterhin propagiert werden, insbesondere unter niedergelassenen Dermatologen.
PubMed: 35881093
DOI: 10.1111/ddg.14758_g -
Thrombosis Journal Jul 2022Appropriate and timely anticoagulant therapy with vitamin K antagonists (VKAs) or non-vitamin K oral antagonists (NOACs) is essential for stroke prevention in...
BACKGROUND
Appropriate and timely anticoagulant therapy with vitamin K antagonists (VKAs) or non-vitamin K oral antagonists (NOACs) is essential for stroke prevention in non-valvular atrial fibrillation (NVAF). Comparative data regarding effectiveness and safety for edoxaban vs phenprocoumon, the predominant VKA in Germany, are scarce.
OBJECTIVES
The study evaluates effectiveness and safety of edoxaban vs phenprocoumon in NVAF patients in a German real-world setting.
METHODS
German statutory health insurance claims data of the Institute for Applied Health Research Berlin (InGef) Research Database from 2014 until 2019 were analyzed. In NVAF patients, new users of edoxaban and phenprocoumon were compared to assess effectiveness (stroke/systemic embolism (SE)) and safety (bleeding) during therapy. Hazard ratios (HR) were estimated through multiple outcome-specific cox proportional hazard models adjusting for baseline characteristics. Outcomes of geriatric patients were analyzed in subgroup analyses.
RESULTS
Between 2015 and 2018, 7,975 and 13,319 NVAF patients newly initiated treatment with edoxaban or phenprocoumon. After adjusting for baseline confounders, the risk of stroke/SE (HR: 0.85, 95% CI: 0.70-1.02) was numerically but not significantly lower, while the risk of major bleeding (HR: 0.69, 95% CI: 0.58-0.81) was significantly lower for edoxaban. In the geriatric subgroups, homogenous results compared to the main analysis were obtained.
CONCLUSION
The results of this real-world analysis indicated better effectiveness and safety outcomes in patients with NVAF initiating edoxaban treatment compared to phenprocoumon. The findings confirm that the beneficial effects observed in the pivotal ENGAGE AF-TMI 48 trial can also be achieved in real-world use of edoxaban.
PubMed: 35787710
DOI: 10.1186/s12959-022-00395-x -
Cellular and Molecular Life Sciences :... Jun 2022Ferroptosis, a type of iron-dependent programmed cell death distinct from apoptosis, necroptosis, and other types of cell death, is characterized by lipid peroxidation,...
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.
Topics: Acute Kidney Injury; Ferroptosis; Humans; Iron; Phenprocoumon; Vitamin K 1
PubMed: 35763128
DOI: 10.1007/s00018-022-04416-w