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Medicina Clinica Jul 2023The objective of the systematic review is to analyze the efficacy of direct-acting oral anticoagulants (DOAC) in the prophylaxis of thrombosis in antiphospholipid... (Review)
Review
The objective of the systematic review is to analyze the efficacy of direct-acting oral anticoagulants (DOAC) in the prophylaxis of thrombosis in antiphospholipid syndrome (APS). We searched for clinical trials, cohort studies and meta-analyses published from January 1, 2012 to September 30, 2022. Articles that analyzed the efficacy of DOAC in the prevention of thrombosis recurrence, with or without comparison with antivitamin K (VKA) drugs, were selected. DOACs, specifically rivaroxaban and apixaban, were significantly less effective than VKAs in preventing recurrence of thrombosis in patients with APS and prior arterial thrombosis or the concomitant presence of two or three different antiphospholipid antibodies. The proportion of patients with severe bleeding as side effect are similar in those treated with DOAC and with VKA. The results argue against the use of DOAC in the treatment of patients with thrombotic APS.
Topics: Humans; Antiphospholipid Syndrome; Anticoagulants; Factor Xa Inhibitors; Warfarin; Thrombosis; Administration, Oral
PubMed: 37105842
DOI: 10.1016/j.medcli.2023.03.011 -
The Journal of the Association of... Oct 2023Warfarin has been the most extensively used oral anticoagulant (OAC) in medical settings for over 60 years. Its uses, potential adverse effects, and methods for... (Review)
Review
Warfarin has been the most extensively used oral anticoagulant (OAC) in medical settings for over 60 years. Its uses, potential adverse effects, and methods for reversing its effects have been firmly established, rendering it a routine medication in medical settings where most professionals feel at ease employing it. Compared to other vitamin K antagonists (VKAs), such as acenocoumarol, warfarin offers benefits like diminished prothrombin time (PT) assays leading to enhanced oral anticoagulation. Observations over the past few years have seen the inclusion of novel/direct OACs (NOACs/DOACs) in the anticoagulant armamentarium. Although DOACs have several advantages, warfarin still has an important role in subsets of patients where DOACs are contraindicated, not well-tolerated, or cannot afford DOACs due to higher costs. Moreover, there are patient profiles where warfarin is still considered a superior choice compared to DOACs, such as age group of >75 years, kidney failure with creatinine clearance (CrCl) below 30 mL/minute, and prosthetic mechanical valve replacement. Precise management of the international normalized ratio (INR) is crucial for the effectiveness of warfarin treatment. INR monitoring is the major concern in the Indian context due to the lack of laboratories for standardized measurement. Adopting strategies such as point-of-care INR monitoring devices and anticoagulation clinics can help to improve clinical outcomes with warfarin therapy. The present review provides a critical overview of the role of warfarin therapy in the current OAC arsenal and strategies for improving therapeutic control and patient adherence. : Nair T. Critical Appraisal on the Role of Warfarin in the Current Era. J Assoc Physicians India 2023;71(10):31-36.
Topics: Humans; Warfarin; Anticoagulants; International Normalized Ratio; Drug Monitoring
PubMed: 38716521
DOI: 10.59556/japi.71.0378 -
Biomedicine & Pharmacotherapy =... Sep 2023Rivaroxaban is a direct inhibitor of factor Xa, a member of direct oral anticoagulant group of drugs (DOACs). Despite being a widely extended alternative to vitamin K...
Rivaroxaban is a direct inhibitor of factor Xa, a member of direct oral anticoagulant group of drugs (DOACs). Despite being a widely extended alternative to vitamin K antagonists (i.e., acenocoumarol, warfarin) the interindividual variability of DOACs is significant, and may be related to adverse drug reaction occurrence or drug inefficacy, namely hemorrhagic or thromboembolic events. Since there is not a consistent analytic practice to monitor the anticoagulant activity of DOACs, previously reported polymorphisms in genes coding for proteins responsible for the activation, transport, or metabolism of DOACs were studied. The study population comprised 60 healthy volunteers, who completed two randomized, crossover bioequivalence clinical trials between two different rivaroxaban formulations. The effect of food, sex, biogeographical origin and 55 variants (8 phenotypes and 47 single nucleotide polymorphisms) in drug metabolizing enzyme genes (such as CYP2D6, CYP2C9, NAT2) and transporters (namely, ABCB1, ABCG2) on rivaroxaban pharmacokinetics was tested. Individuals dosed under fasting conditions presented lower t (2.21 h vs 2.88 h, β = 1.19, R =0.342, p = 0.012) compared to fed volunteers. NAT2 slow acetylators presented higher AUC corrected by dose/weight (AUC/DW; 8243.90 vs 7698.20 and 7161.25 h*ng*mg /ml*kg, β = 0.154, R =0.250, p = 0.044), higher C/DW (1070.99 vs 834.81 and 803.36 ng*mg /ml*kg, β = 0.245, R =0.320, p = 0.002), and lower t (2.63 vs 3.19 and 4.15 h, β = -0.346, R =0.282, p = 0.047) than NAT2 rapid and intermediate acetylators. No other association was statistically significant. Thus, slow NAT2 appear to have altered rivaroxaban pharmacokinetics, increasing AUC and C. Nonetheless, further research should be conducted to verify NAT2 involvement on rivaroxaban pharmacokinetics and to determine its clinical significance.
Topics: Humans; Rivaroxaban; Healthy Volunteers; Anticoagulants; Polymorphism, Single Nucleotide; Phenotype; Arylamine N-Acetyltransferase
PubMed: 37385211
DOI: 10.1016/j.biopha.2023.115058 -
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 -
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 -
Research in Social & Administrative... Dec 2023Interdisciplinary collaboration between general practitioner, nurses and pharmacists can favour the control of patients treated with vitamin K antagonists (VKA),...
Clinical, economic, and humanistic impact of a multidisciplinary medication review with follow-up for anticoagulated patients treated with vitamin K antagonists in primary care: A cluster randomised controlled trial.
BACKGROUND
Interdisciplinary collaboration between general practitioner, nurses and pharmacists can favour the control of patients treated with vitamin K antagonists (VKA), increasing their safety and effectiveness. The aim of the study was to evaluate the impact of pharmaceutical interventions on patients treated with VKA within the framework of a Pharmacotherapeutic Follow-up service on clinical, economic and humanistic outcomes.
METHODS
Controlled and randomized study in patients from two health areas of Zaragoza in treatment with VKA with Time in Therapeutic Range (TTR) according to the Rosendaal method less than 70% in the last 6 months. Patients were recruited at the pharmacy and assigned to two groups: control and intervention. A Pharmacotherapeutic Follow-up Program was established for the intervention group for 6 months. The outcome variables were INR stability, pharmacological adherence, vitamin K intake, knowledge about the use of acenocoumarol, quality of life, satisfaction with treatment, associated costs and avoided costs. A descriptive analysis was performed, and the Students' T test or Mann-Whitney U test was used for the association between quantitative variables and Chi-square or Fisher's test for qualitative variables.
RESULTS
A total of 123 patients were included, 65 in the intervention group (IG) and 58 in the control group (CG). A total of 108 interventions were conducted (1.7 interventions/patient) and the most common were those related to the proper taking of medications (41.0%). In IG, TTR (p = 0.019), adherence to treatment (p = 0.038) and knowledge about acenocoumarol (p = 0.031) improved, compared to CG. A higher proportion of patients in IG achieved a TTR>65% (p = 0.024). In addition, patients whose interventions were accepted by the physician (p = 0.027) and those who received vitamin K optimization interventions (p = 0.003) achieved TTR>65% in greater proportion.
CONCLUSIONS
Community pharmacist medication review, in collaboration with general practitioners improve knowledge and adherence of patients treated with oral anti-vitamin K agents and enhances the achievement of their therapeutic INR ranges. Investment needed to achieve this clinical impact is low and patient satisfaction is high.
TRIAL REGISTRATION
This study has been registered with Clinical Trials.gov dated 25/05/2017: NCT03154489.
PubMed: 37704534
DOI: 10.1016/j.sapharm.2023.08.007 -
Cureus Jan 2024Acenocoumarol is one of the most common drugs used as a part of the management of patients undergoing cardiac surgery. Linezolid, on the other hand, is an antibiotic...
Acenocoumarol is one of the most common drugs used as a part of the management of patients undergoing cardiac surgery. Linezolid, on the other hand, is an antibiotic prescribed post-operatively. Reports of any interaction between the two are very few. Here, we are presenting four case reports of patients admitted to the Cardio Thoracic and Vascular Surgery Department of a tertiary healthcare center in North East India. Drug-drug interactions can lead to long-term and life-threatening effects, and also hamper the management of patients post-operatively. Due to the limited literature, assessing such interactions is difficult. The cases reported here were treated with fresh frozen plasma, and the patients responded well to the treatment and were discharged without further complications.
PubMed: 38264177
DOI: 10.7759/cureus.52753 -
Revista Clinica Espanola Jun 2024Oral anticoagulation (OAC) is key in atrial fibrillation (AF) thromboprophylaxis, but Spain lacks substantial real-world evidence. We aimed to analyze the prevalence,...
INTRODUCTION
Oral anticoagulation (OAC) is key in atrial fibrillation (AF) thromboprophylaxis, but Spain lacks substantial real-world evidence. We aimed to analyze the prevalence, clinical characteristics, and treatment patterns among patients with AF undertaking OAC, using natural language processing (NLP) and machine learning (ML).
MATERIALS AND METHODS
This retrospective study included AF patients on OAC from 15 Spanish hospitals (2014-2020). Using EHRead® (including NLP and ML), and SNOMED_CT, we extracted and analyzed patient demographics, comorbidities, and OAC treatment from electronic health records. AF prevalence was estimated, and a descriptive analysis was conducted.
RESULTS
Among 4,664,224 patients in our cohort, AF prevalence ranged from 1.9% to 2.9%. A total of 57,190 patients on OAC therapy were included, 80.7% receiving Vitamin K antagonists (VKA) and 19.3% Direct-acting OAC (DOAC). The median age was 78 and 76 years respectively, with males constituting 53% of the cohort. Comorbidities like hypertension (76.3%), diabetes (48.0%), heart failure (42.2%), and renal disease (18.7%) were common, and more frequent in VKA users. Over 50% had a high CHA2DS2-VASc score. The most frequent treatment switch was from DOAC to acenocoumarol (58.6% to 70.2%). In switches from VKA to DOAC, apixaban was the most chosen (35.2%).
CONCLUSIONS
Utilizing NLP and ML to extract RWD, we established the most comprehensive Spanish cohort of AF patients with OAC to date. Analysis revealed a high AF prevalence, patient complexity, and a marked VKA preference over DOAC. Importantly, in VKA to DOAC transitions, apixaban was the favored option.
PubMed: 38849073
DOI: 10.1016/j.rceng.2024.06.002 -
Archivio Italiano Di Urologia,... Oct 2023Renal artery infarction (RI) is the presence of blood clot in the main renal artery or its branches causing complete or partial obstruction of the blood supply. Its...
AIM
Renal artery infarction (RI) is the presence of blood clot in the main renal artery or its branches causing complete or partial obstruction of the blood supply. Its etiology is either related with disorders of the renal vasculature or with cardiovascular diseases. Recently, the SARSCoV- 2 virus is an emerging cause of thromboembolic events and the incidence of RI is anticipated to increase after the pandemic.
METHODS
A systematic review based on COVID-19 associated RI was conducted.
PROTOCOL
A systematic review of the Medline/Pubmed and Scopus databases was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (the PRISMA statement). Search strategy and information sources: A hand-search was performed using the terms "SARS-Cov-2" OR "COVID-19" AND "renal thrombosis" OR "renal infarction" OR "renal "thromboembolism".
ELIGIBILITY CRITERIA
all types of publications (case reports, case series, letters to the editor, short communications) were evaluated for relevance. Inclusion criteria were: confirmed SARS-Cov-2 infection irrespectively of the age, diagnosis of RI during or after the onset of viral infection, and exclusion of other potential causes of thromboembolic event except of SARS-Cov-2. Patients with renal transplantation were also considered. Study criteria selection: after checking for relevance based on the title and the abstract, the full texts of the selected papers were retrieved and were further evaluated. Duplicated and irrelevant cases were excluded. Any disagreement was resolved by consensus with the involvement of a third reviewer. Quality of studies: The assessment of the quality case reports was based on four different domains: selection, ascertainment, casualty and reporting. Each paper was classified as "Good", "Moderate" and "Poor" for any of the four domains. Data extractions: Crucial data for the conduct of the study were extracted including: age, sex, time from SARS-Cov-2 infection till RI development, medical history, previous or current antithrombotic protection or treatment, laterality and degree of obstruction, other sites of thromboembolism, treatment for thromboembolism and SARS-Cov-2 and final outcome.
DATA ANALYSIS
methods of descriptive statistics were implicated for analysis and presentation of the data.
RESULTS
The systematic review retrieved 35 cases in 33 reports. In most cases, RI was diagnosed within a month from the SARSCov- 2 infection albeit 17 out of 35 patients were receiving or had recently received thromboprophylaxis. Right, left, bilateral and allograft obstruction was diagnosed in 7, 15, 8 and 5 patients respectively. 17 cases experienced additional extrarenal thromboembolism primarily in aorta, spleen, brain and lower limbs. Low molecular weight heparins (LMWH) (usually 60-80 mg enoxaparine bid) was the primary treatment, followed by combinations of unfractionated heparin and salicylic acid, apixaban and rivaraxaban, warfarin, acenocoumarol or clopidogrel. Kidney replacement therapy was offered to five patients while invasive therapies with thrombus aspiration or catheter directed thrombolysis were performed in two. Regarding the outcomes, five of the patients died. The total renal function was preserved in 17 cases and renal impairment with or without hemodialysis was recorded in 5 patients, two of them having lost their kidney allografts.
LIMITATIONS
The majority of included studies are of moderate quality. The results and the conclusions are based on case-reports only and crucial data are dissimilarly presented or missing through the relevant publications.
CONCLUSIONS
Thromboprophylaxis may not offer adequate protection against SARS-Cov-2 induced thrombosis. Most patients could be effectively treated with conservative measures, while in more severe cases aggressive treatment could be recommended.
IMPLICATIONS OF KEY FINDINGS
Therapeutic doses of LMWH could be considered for protection against RI in SARS-Cov-2 cases. Interventional treatment could be offered in a minority of more severe cases after carful balancing the risks and benefits.
Topics: Humans; SARS-CoV-2; COVID-19; Heparin, Low-Molecular-Weight; Anticoagulants; Heparin; Renal Artery; Venous Thromboembolism; Thrombosis; Infarction
PubMed: 37791549
DOI: 10.4081/aiua.2023.11625 -
Thrombosis Research Aug 2023The European Medicine Agency has authorized COVID-19 vaccination in adolescents and young adults (AYAs) from 12 years onwards. In elderly vitamin K antagonist (VKA)...
INTRODUCTION
The European Medicine Agency has authorized COVID-19 vaccination in adolescents and young adults (AYAs) from 12 years onwards. In elderly vitamin K antagonist (VKA) users, COVID-19 vaccination has been associated with an increased risk of supra- and subtherapeutic INRs. Whether this association is also observed in AYAs using VKA is unknown. Our aim was to describe the stability of anticoagulation after COVID-19 vaccination in AYA VKA users.
MATERIALS AND METHODS
A case-crossover study was performed in a cohort of AYAs (12-30 years) using VKAs. The most recent INR results before vaccination, the reference period, were compared with the most recent INR after the first and, if applicable, second vaccination. Several sensitivity analyses were performed in which we restricted our analysis to stable patients and patients without interacting events.
RESULTS
101 AYAs were included, with a median age [IQR] of 25 [7] years, of whom 51.5 % were male and 68.3 % used acenocoumarol. We observed a decrease of 20.8 % in INRs within range after the first vaccination, due to an increase of 16.8 % in supratherapeutic INRs. These results were verified in our sensitivity analyses. No differences were observed after the second vaccination compared to before and after the first vaccination. Complications after vaccination occurred less often than before vaccination (9.0 vs 3.0 bleedings) and were non-severe.
CONCLUSIONS
the stability of anticoagulation after COVID-19 vaccination was decreased in AYA VKA users. However, the decrease might not be clinically relevant as no increase of complications nor significant dose adjustments were observed.
Topics: Humans; Male; Young Adult; Adolescent; Aged; Adult; Female; COVID-19 Vaccines; Cross-Over Studies; COVID-19; Anticoagulants; International Normalized Ratio; Vitamin K
PubMed: 37321159
DOI: 10.1016/j.thromres.2023.06.005