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Journal of Comparative Effectiveness... Aug 2023Healthcare resources usage and costs associated to nonvalvular atrial fibrillation (NVAF) were analyzed in Spain. This is an observational and retrospective study on... (Observational Study)
Observational Study
Healthcare resources usage and costs associated to nonvalvular atrial fibrillation (NVAF) were analyzed in Spain. This is an observational and retrospective study on patients with NVAF who started their treatment with apixaban or acenocoumarol between 1 January 2015 and 31 December 2017. 2160 patients treated with apixaban were paired (1:1) with patients treated with acenocoumarol (propensity score matching). Apixaban reduced the incidence of strokes and systemic embolisms, minor and major bleedings and deaths, versus acenocoumarol. Apixaban led to reductions of 80, 55 and 43% in costs related to nursing visits, hospitalizations, and emergency visits, respectively, leading to annual cost savings of €274/patient, from the perspective of society. Our results suggested that apixaban is a cost-effective alternative for patients with NVAF.
Topics: Humans; Acenocoumarol; Atrial Fibrillation; Anticoagulants; Spain; Retrospective Studies; Pyridones; Stroke; Delivery of Health Care; Rivaroxaban
PubMed: 37489950
DOI: 10.57264/cer-2023-0007 -
Molecules (Basel, Switzerland) Feb 2023The repurposing of already-approved drugs has emerged as an alternative strategy to rapidly identify effective, safe, and conveniently available new therapeutic...
The repurposing of already-approved drugs has emerged as an alternative strategy to rapidly identify effective, safe, and conveniently available new therapeutic indications against human diseases. The current study aimed to assess the repurposing of the anticoagulant drug acenocoumarol for the treatment of chronic inflammatory diseases (e.g., atopic dermatitis and psoriasis) and investigate the potential underlying mechanisms. For this purpose, we used murine macrophage RAW 264.7 as a model in experiments aimed at investigating the anti-inflammatory effects of acenocoumarol in inhibiting the production of pro-inflammatory mediators and cytokines. We demonstrate that acenocoumarol significantly decreases nitric oxide (NO), prostaglandin (PG)E, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Acenocoumarol also inhibits the expression of NO synthase (iNOS) and cyclooxygenase (COX)-2, potentially explaining the acenocoumarol-induced decrease in NO and PGE production. In addition, acenocoumarol inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs), c-Jun N terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK), in addition to decreasing the subsequent nuclear translocation of nuclear factor κB (NF-κB). This indicates that acenocoumarol attenuates the macrophage secretion of TNF-α, IL-6, IL-1β, and NO, inducing iNOS and COX-2 expression via the inhibition of the NF-κB and MAPK signaling pathways. In conclusion, our results demonstrate that acenocoumarol can effectively attenuate the activation of macrophages, suggesting that acenocoumarol is a potential candidate for drug repurposing as an anti-inflammatory agent.
Topics: Animals; Mice; Acenocoumarol; Anti-Inflammatory Agents; Cyclooxygenase 2; Extracellular Signal-Regulated MAP Kinases; Interleukin-6; Lipopolysaccharides; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; RAW 264.7 Cells; Tumor Necrosis Factor-alpha
PubMed: 36903321
DOI: 10.3390/molecules28052075 -
Annals of Cardiac Anaesthesia 2022The aim of this study is to analyze anticoagulation-related complications in patients following mechanical valve replacement and factors influencing the outcome.
PURPOSE
The aim of this study is to analyze anticoagulation-related complications in patients following mechanical valve replacement and factors influencing the outcome.
MATERIALS AND METHODS
A total of 250 patients were analyzed during OPD follow-up for anticoagulation-related complications and various factors influencing outcome. Patients received prosthetic valve at mitral and/or aortic or both.
RESULTS
Out of 250 patients, 48% were male and 52% were female. The mean age was 41.9 ± 14.4. A total of 139 had mitral valve replacement (MVR), 70 had aortic valve replacement (AVR), 40 had double valve replacement (DVR), and 1 patient had triple valve replacement. Valves implanted were mechanical bileaflet valve. The mean international normalization ratio (INR) in the study was 2.4 ± 0.56. A total of 49 events occurred during follow-up, of which 4.5% per patient years were anticoagulation-related hemorrhagic events and 4.8% per patient years were thromboembolic events. Among thromboembolic events, valve thrombosis occurred in 10 patients and cerebrovascular accidents occurred in 11 patients. Mean INR for thromboembolic events was 1.46 ± 0.25 and anticoagulation-related hemorrhagic events was 4.4 ± 1.03. Mortality rate was 1.6% in AVR, 4% in MVR, and 0.4% in DVR groups; about 34% of patients needed dose modification of Acenocoumarol and reason for derangement of INR was associated with infectious process and poor compliance; 85% of cases showed good compliance for daily anticoagulation therapy.
CONCLUSION
Anticoagulation for mechanical valve replacement can be managed with INR range of 2.0 to 2.5 in MVR and 1.5 to 2.0 in AVR with acceptable hemorrhagic and thromboembolic events. We must educate and counsel the patients during follow-up for better compliance to optimal anticoagulation.
Topics: Adult; Anticoagulants; Aortic Valve; Female; Follow-Up Studies; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Thromboembolism
PubMed: 35075023
DOI: 10.4103/aca.aca_125_21 -
Cureus Apr 2023Diffuse alveolar hemorrhage (DAH) is bleeding into the alveolar spaces of the lung. DAH is often associated with systemic autoimmune diseases, coagulation disorders,...
Diffuse alveolar hemorrhage (DAH) is bleeding into the alveolar spaces of the lung. DAH is often associated with systemic autoimmune diseases, coagulation disorders, drugs, inhaled toxins, or transplantation. This study describes a rare case of acenocoumarol-induced DAH, a pulmonary disorder, which has not been reported before. A 48-year-old male presented with a history of rheumatic heart disease with mitral stenosis with moderate mitral regurgitation status post mitral valve replacement. He was taking acenocoumarol but did not keep his prothrombin time-international normalized ratio (PT-INR) monitoring and came to the hospital with complaints of cough, hemoptysis, and breathlessness. Chest x-ray and high-resolution computed tomography (HRCT) thorax were done which revealed diffuse patchy opacities and pulmonary hemorrhage, respectively. After nine days of hospital stay with appropriate management with corticosteroids, antibiotics, and intravenous fluids, the patient was doing well.
PubMed: 37193442
DOI: 10.7759/cureus.37581 -
Hellenic Journal of Cardiology : HJC =... 2021To estimate the incidence of hemorrhagic events in patients with atrial fibrillation (AF) treated with acenocoumarol, and the management cost of those requiring...
BACKGROUND
To estimate the incidence of hemorrhagic events in patients with atrial fibrillation (AF) treated with acenocoumarol, and the management cost of those requiring hospitalization in Greece.
METHODS
A nationwide telephone survey was conducted between December 2017 and January 2018, to identify cardiologists who treat AF patients with acenocoumarol. A total of 300 cardiologists were selected and reported the number of AF acenocoumarol-treated patients during the past 12 months and the number of those who experienced a hemorrhagic event. The hospital charges to sickness fund and the cost of resource utilization of AF patients hospitalized between January 2013 and June 2017 at a tertiary hospital in Athens due to acenocoumarol-related bleedings were retrieved.
RESULTS
Out of 48,255 AF patients, 12,633 (26.2%) were treated with acenocoumarol. In all, 5.1% of patients experienced a hemorrhagic event with the incidence of bleeding requiring hospitalization being 1.7%. The most common bleeding site was the gastrointestinal system (51.5%). The mean (95% CI) management cost per bleeding event requiring hospitalization was €1,202 (€1,058-€1,420). The higher cost was that of intracranial bleeding €3,887 (€2,700-€5,046). The expected annual economic burden for the management of bleedings related to acenocoumarol and requiring hospitalization was estimated at €1,463,955.
CONCLUSIONS
The incidence of bleeding events in AF acenocoumarol-treated patients in Greece as well as the estimated annual economic burden for the management of bleeding events requiring hospitalization, emphasize the need to comply with the current guidelines and to optimize therapeutic strategies for the management of AF side effects with oral anticoagulants, particularly in patients with high bleeding risk.
Topics: Acenocoumarol; Anticoagulants; Atrial Fibrillation; Greece; Hospitalization; Humans; Incidence; Retrospective Studies; Stroke
PubMed: 32683128
DOI: 10.1016/j.hjc.2020.06.013 -
Anales Del Sistema Sanitario de Navarra Aug 2020Infection caused by SARS-CoV-2 (COVID-19) is associated with an increased risk of thromboembolic disease. So-me authors recommend anticoagulation at therapeutic doses...
Infection caused by SARS-CoV-2 (COVID-19) is associated with an increased risk of thromboembolic disease. So-me authors recommend anticoagulation at therapeutic doses for, at least, the most severely ill patients; this practice is not free of risks, which is why only thromboembolic prophylaxis is recommended by other consensuses. In the case of previously anticoagulated patients, changing the oral anticoagulant for a low molecular weight heparin (LMWH) is generally recommended. We present the cases of two patients admitted due to COVID-19, without serious clinical data, in whom anticoagulation (acenocoumarol and rivaroxaban, respectively) was replaced by LMWH at therapeutic doses, both presenting abdominal bleeding. This type of bleeding is an infrequent complication in anticoagulated patients, but the concurrence of two cases in a short period of time in the context of the COVID-19 pandemic leads us to consider that there is not yet any clear evidence on therapeutic anticoagulation in SARS-CoV-2 infection.
Topics: Abdomen; Acenocoumarol; Aged, 80 and over; Anticoagulants; Betacoronavirus; COVID-19; Coronavirus Infections; Female; Hematoma; Heparin, Low-Molecular-Weight; Humans; Pandemics; Pneumonia, Viral; Rivaroxaban; SARS-CoV-2; Venous Thromboembolism
PubMed: 32865189
DOI: 10.23938/ASSN.0884 -
World Journal of Cardiology Nov 2022Since 2010, the European Society of Cardiology has extended prescription criteria for oral antithrombotic therapy (OAT) in atrial fibrillation (AF). Direct oral...
BACKGROUND
Since 2010, the European Society of Cardiology has extended prescription criteria for oral antithrombotic therapy (OAT) in atrial fibrillation (AF). Direct oral anticoagulants (DOACs) were upgraded from an IIAa recommendation in 2012 to an IA in 2016. In real-world scenarios, however, OAC prescription is still suboptimal, mainly for DOACs.
AIM
To evaluate OAT temporal prescription patterns in a cohort of patients hospitalized with AF in a Cardiology Department.
METHODS
A retrospective observational study was conducted on a cohort of hospitalized patients in a secondary setting (Trapani, Italy) from 2010 to 2021 with AF as the main or secondary diagnosis. For 4089 consecutive patients, the variables extracted from the Cardiology department database were: Sex, age, time of hospitalization, antithrombotic therapy (warfarin, acenocoumarol, apixaban, dabigatran, edoxaban, rivaroxaban, aspirin, clopidogrel, other antiplatelet agents, low molecular weight heparin, and fondaparinux), diagnosis at discharge and used resources. Basal features are presented as percentage values for categorized variables and as mean +/- SD for categorized once.
RESULTS
From January 1st, 2010 to October 6th, 2021, 25132 patients were hospitalized in our department; 4089 (16.27%, mean age 75.59+/-10.82) were discharged with AF diagnosis; of them, 2245 were males (54.81%, mean age 73.56+/-11.45) and 1851 females (45.19%, mean age 78.06+/-9.47). Average length of stay was 5.76+/-4.88 days; 154 patients died and 88 were moved to other Departments/Structures. AF was the main diagnosis in 899 patients (21.94%). The most frequent main diagnosis in patients with AF was acute myocardial infarction (1973 discharges, 48.19%). The most frequent secondary cardiac diagnosis was chronic coronary syndrome (1864 discharges, 45.51%), and the most frequent secondary associated condition was arterial hypertension (1010 discharges, 24.66%). For the analysis of antithrombotic treatments, the final sample included 3067 patients, after excluding in-hospital deaths, transferred out or self-discharged patients, as well as discharges lacking indications for prescribed treatments. OAC treatment increased significantly (35.63% in 2010-2012 61.18% in 2019-2021, +25.55%, < 0.0001), in spite of any antiplatelet agent use. This rise was due to increasing use of DOACs, with or without antiplatelet agents, from 3.04% in 2013-2015 to 50.06% in 2019-2021 (+47.02%, < 0.0001) and was greater for factor Xa inhibitors, especially apixaban. In addition, treatment with a vitamin K antagonist, in spite of any antiplatelet agent use, decreased from 35.63% in 2010-2012 to 11.12% in 2019-2021 (-24.48%, < 0.0001), as well as any antiplatelet therapy, alone or in double combination, (49.18% in 2010-2012 34.18% in 2019-2021, -15.00%, < 0.0001); and patients not receiving antithrombotic therapy declined with time (14.58% in 2010-2012 1.97% in 2021, < 0.0001).
CONCLUSION
Real-world patients with AF are elderly and affected by cardiovascular and non-cardiovascular diseases. The percentage of patients on OAT and DOACs increased. These data suggest a slow, gradual guidelines implementation process.
PubMed: 36483763
DOI: 10.4330/wjc.v14.i11.576 -
Journal of Physiology and Pharmacology... Aug 2023Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the...
Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be important therapeutic agents. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to determine whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 μg/kg) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of AP was assessed immediately after the last dose of cerulein, as well as at days 1, 2, 3, 5, and 10 after AP induction. Treatment with warfarin dose-dependently increased international normalized ratio (INR) and attenuated the severity of pancreatitis in histological examination and accelerated pancreatic recovery. These effects were accompanied with a faster reduction in the AP-evoked increase in serum activity of amylase and lipase, the serum concentration of pro-inflammatory interleukin-1β, and the plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight (an index of pancreatic edema) and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 μg/kg. We conclude that treatment with warfarin accelerated regeneration of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.
Topics: Rats; Male; Animals; Pancreatitis; Warfarin; Ceruletide; Rats, Wistar; Acenocoumarol; Acute Disease; Pancreas
PubMed: 37865961
DOI: 10.26402/jpp.2023.4.08 -
Molecules (Basel, Switzerland) Mar 2021Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some... (Comparative Study)
Comparative Study Observational Study
Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, < 0.001). A higher prevalence of TiTR (<60%, <65%, or <70%) was found in acenocoumarol users than in warfarin ones ( < 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin.
Topics: Acenocoumarol; Aged; Anticoagulants; Blood Coagulation; Female; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Middle Aged; Retrospective Studies; Venous Thromboembolism; Warfarin
PubMed: 33800767
DOI: 10.3390/molecules26051425 -
Medical Cannabis and Cannabinoids 2023Treatment with cannabis extracts for a variety of diseases has gained popularity. However, differences in herb-drug interaction potential of extracts from different...
INTRODUCTION
Treatment with cannabis extracts for a variety of diseases has gained popularity. However, differences in herb-drug interaction potential of extracts from different plant sources are poorly understood. In this study, we provide a characterization of cannabis extracts prepared from four cannabis chemotypes and an in vitro assessment of their Cytochrome P450 (CYP)-mediated herb-drug interaction profiles.
METHODS
Plant extracts were either commercially obtained or prepared using ethanol as solvent, followed by overnight decarboxylation in a reflux condenser system. The extracts were characterized for their cannabinoid content using NMR and HPLC-PDA-ELSD-ESIMS. CYP inhibition studies with the cannabis extracts and pure cannabinoids (tetrahydrocannabinol [THC] and cannabidiol [CBD]) were performed using pooled, mixed gender human liver microsomes. Tolbutamide and testosterone were used as specific substrates to assess the inhibitory potential of the extracts on CYP2C9 and CYP3A4, and the coumarinic oral anticoagulants warfarin, phenprocoumon, and acenocoumarol were studied as model compounds since in vivo herb-drug interactions have previously been reported for this compound class.
RESULTS
In accordance with the plant chemotypes, two extracts were rich in THC and CBD (at different proportions); one extract contained mostly CBD and the other mostly cannabigerol (CBG). Residual amounts of the corresponding acids were found in all extracts. The extracts with a single major cannabinoid (CBD or CBG) inhibited CYP2C9- and CYP3A4-mediated metabolism stronger than the extracts containing both major cannabinoids (THC and CBD). The inhibition of CYP3A4 and CYP2C9 by the extract containing mostly CBD was comparable to their inhibition by pure CBD. In contrast, the inhibitory potency of extracts containing both THC and CBD did not correspond to the combined inhibitory potency of pure THC and CBD. Although being structural analogs, the three coumarin derivatives displayed major differences in their herb-drug interaction profiles with the cannabis extracts and the pure cannabinoids.
CONCLUSION
Despite the fact that cannabinoids are the major components in ethanolic, decarboxylated cannabis extracts, it is difficult to foresee their herb-drug interaction profiles. Our in vitro data and the literature-based evidence on in vivo interactions indicate that cannabis extracts should be used cautiously when co-administered with drugs exhibiting a narrow therapeutic window, such as coumarinic anticoagulants, regardless of the cannabis chemotype used for extract preparation.
PubMed: 36814687
DOI: 10.1159/000528465