-
Drugs & Aging Jul 2020Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age... (Review)
Review
A Structured Literature Review and International Consensus Validation of FORTA Labels of Oral Anticoagulants for Long-Term Treatment of Atrial Fibrillation in Older Patients (OAC-FORTA 2019).
INTRODUCTION
Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age appropriateness of oral anticoagulants (OAC) according to the FORTA (Fit fOR The Aged) classification (OAC-FORTA). Three years after its first version (OAC-FORTA 2016), an update was initiated to create OAC-FORTA 2019.
METHODS
A structured review of randomized controlled clinical trials and summaries of individual product characteristics was performed to detect newly emerged evidence on oral anticoagulants in older patients with AFib. This review was used by an interdisciplinary panel of European experts (N = 10) in a Delphi process to label OACs according to FORTA.
RESULTS
A total of 202 records were identified and 11 studies finally included. We found four new trials providing relevant data on efficacy and safety of warfarin, apixaban, dabigatran or rivaroxaban in older patients with AFib. In the majority of studies comparing the non-vitamin-K oral anticoagulants (NOACs) with warfarin, NOACs were superior to warfarin regarding at least one relevant clinical endpoint. The mean consensus coefficient significantly increased from 0.867 (OAC-FORTA 2016) to 0.931 (p < 0.05) and the proposed FORTA classes were confirmed in all cases during the first round (consensus coefficient > 0.8). Warfarin, dabigatran, edoxaban and rivaroxaban were assigned to the FORTA B label, acenocoumarol, fluindione and phenprocoumon were labeled FORTA C and only apixaban was rated as FORTA A.
CONCLUSION
OAC-FORTA 2019 confirms that AFib can be successfully treated with positively labeled antithrombotics at advanced age.
Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Consensus Development Conferences as Topic; Dabigatran; Europe; Female; Humans; Long-Term Care; Male; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Vitamin K; Warfarin
PubMed: 32500503
DOI: 10.1007/s40266-020-00771-0 -
Frontiers in Pharmacology 2020Vitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and...
BACKGROUND
Vitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and acenocoumarol. These drugs have a narrow therapeutic margin and high inter-individual response variability due to clinical and pharmacogenetic variables.
OBJECTIVE
The authors aim to develop an algorithm comprised of clinical and genetic factors to explain the variability in the therapeutic dose of acenocoumarol among Chilean patients.
METHODOLOGY
DNA was obtained from 304 patients as a discovery cohort with an international normalized ratio (INR) range of 2.0-3.0. The non-genetic (demographic and clinical) variables were also recorded. Genotype analyses were performed using real-time PCR for (), (), () () () (), (), and ().
RESULTS
The clinical variables that significantly influenced the weekly therapeutic dose of VKA were age, sex, body mass index (BMI), and initial INR, collectively accounting for 19% of the variability, and the genetic variables with a significant impact were (), (), and (), explaining for another 37% of the variability.
CONCLUSION
We developed an algorithm that explains 49.99% of the variability in therapeutic VKA dosage in the Chilean population studied. Factors that significantly affected the dosage included , , and polymorphisms, as well as age, sex, BMI, and initial INR.
PubMed: 32327994
DOI: 10.3389/fphar.2020.00325 -
Chemical Communications (Cambridge,... May 2023An efficient approach for the direct synthesis of alkylated 4-hydroxycoumarin derivatives a Cu-catalyzed cascade dehydrogenation/conjugate addition sequence starting...
An efficient approach for the direct synthesis of alkylated 4-hydroxycoumarin derivatives a Cu-catalyzed cascade dehydrogenation/conjugate addition sequence starting from simple saturated ketones and 4-hydroxycoumarins has been developed. This protocol features excellent functional-group tolerance, easy scale-up, and a broad substrate scope including bioactive molecules. More importantly, a series of marketed drugs, such as warfarin, acenocoumarol, coumachlor, and coumafuryl, can be obtained by this method.
PubMed: 37183637
DOI: 10.1039/d3cc01960h -
Biomedica : Revista Del Instituto... Sep 2021We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of...
We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of acenocoumarol, as well as other values reported as uncoagulable, forcing the discontinuation and restart of treatment more than once. Expected and stable INR levels were achieved after more than 30 days of treatment, surprisingly with half the recommended dose for a patient of her age and weight. We decided to conduct a retrospective pharmacogenomic analysis including nucleotide genetic polymorphisms (SNPs) with different degrees of association with the dose/response to antivitamin K (AVK) drugs: rs2108622 (gene CYP4F2), rs9923231, rs7294 (gene VKORC1), rs1799853, and rs1057910 (CYP2C9 gene) using TaqMan® RT-PCR. The patient was homozygous for rs9923231 (VKORC1) and heterozygous for rs2108622 (CYP4F2),a genetic profile strongly associated with a requirement of lower AVK doses as shown by national and international evidence. In conclusion, the pharmacogenetic analysis confirmed that this patient’s genetic conditions, involving low expression of the VKA therapeutic target, required a lower dose than that established in clinical protocols as recommended by the Food and Drug Administration (FDA) and the PharmGKB® for coumarin drugs. A previous genotypic analysis of the patient would have allowed reaching the therapeutic range sooner, thus avoiding potential bleeding risks. This shows the importance of pharmacogenetic analyses for highly variable treatments with a narrow therapeutic range.
Topics: Anticoagulants; Child; Female; Genotype; Humans; Pharmacogenomic Testing; Polymorphism, Single Nucleotide; Retrospective Studies; Vitamin K Epoxide Reductases
PubMed: 34559488
DOI: 10.7705/biomedica.5840 -
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 -
Revista Medica de Chile Sep 2020Vitamin K antagonist medications (VKA) are essential for the prevention of thromboembolic events, but their effectiveness is influenced by multiple factors, such as the...
BACKGROUND
Vitamin K antagonist medications (VKA) are essential for the prevention of thromboembolic events, but their effectiveness is influenced by multiple factors, such as the type of medication chosen.
AIM
To evaluate the efficacy in anticoagulant control of the bioequivalent and non-bioequivalent drugs of acenocoumarol compared to the reference drug. To evaluate the efficacy of warfarin bioequivalents available in Chile. To contrast the overall anticoagulant control efficacy between acenocoumarol and warfarin.
MATERIAL AND METHODS
The results of 69333 outpatient oral anticoagulation controls were analyzed. Patient were separated in groups according to the drug that they used. Subsequently, the proportions of controls outside the range for each of acenocoumarol and warfarin bioequivalent drugs were compared. Acenocoumarol non-bioequivalent drugs were also compared with the reference drug. Acenocoumarol was compared with warfarin.
RESULTS
Acenocoumarol bioequivalent drugs and the reference drug had a similar proportion of controls outside the range (Odds ratios (OR) 0.812; 0.969; 0.974 and 0.963). Non-bioequivalent drugs had a higher proportion than the reference drug (OR 1.561 and 2.037). Both warfarin brands have a similar proportion of controls outside of the range (OR 1.050). Acenocoumarol compared to warfarin had a significant higher proportion of controls outside the range (OR 1.191).
CONCLUSIONS
The pharmacological presentation of vitamin K antagonists could influence anticoagulant control. Therefore, it is not prudent to switch these presentations frequently.
Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Chile; Humans; Thromboembolism; Vitamin K
PubMed: 33399700
DOI: 10.4067/S0034-98872020000901254 -
Pharmacogenomics Jun 2022Vitamin K antagonists (VKAs) are class I oral anticoagulants that are widely prescribed following surgical heart valve implantation. The objective of this study was to...
Vitamin K antagonists (VKAs) are class I oral anticoagulants that are widely prescribed following surgical heart valve implantation. The objective of this study was to quantify the relative effects of and genotypes in predicting VKA dosing. A total of 506 South Indian patients with mechanical prosthetic heart valves who were prescribed oral VKAs, such as warfarin or acenocoumarol, were genotyped. The discriminatory ability of mutant genotypes to predict dose categories and bleeding events was assessed using regression analysis. The rs9923231, and mutant genotypes significantly influenced VKA-dose requirements and explained 27.47% of the observed dose variation. These results support pharmacogenetic screening for initial VKA dosing among South Indian patients with mechanical prosthetic heart valves.
Topics: Anticoagulants; Cytochrome P-450 CYP2C9; Genotype; Heart Valves; Humans; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Vitamin K; Vitamin K Epoxide Reductases
PubMed: 35608144
DOI: 10.2217/pgs-2022-0014 -
Thrombosis Research Jul 2021Time in therapeutic range (TTR) measures the stability of the international normalized ratio in patients on vitamin K antagonists (VKA). Low values are associated with...
BACKGROUND
Time in therapeutic range (TTR) measures the stability of the international normalized ratio in patients on vitamin K antagonists (VKA). Low values are associated with poor outcomes. Women were shown to have lower TTR than men, but the causes are poorly defined. It was suggested that women on VKA are older and more morbid than men, and this could affect the stability of anticoagulation. We aimed to identify variables that affect TTR differently in women and men.
MATERIALS AND METHODS
This is a retrospective study in patients referred to a University hospital anticoagulant clinic. Age, sex, comorbidities, number of daily medications, indication and type of anticoagulant, weekly dosage and distribution, were derived from electronic records. Differences by sex and regression analysis to identify significant modulators of TTR were computed.
RESULTS
1182 women and 1281 men on VKA were studied. Women were older than men (81.5 yrs. ± 11.2 vs 78.4 yrs. ± 12.2), and had lower TTR (65% ± 20.3 vs 69% ± 19.8). Comorbidity was similar between sexes and negatively affected TTR in both. Mechanical valves as an indication to anticoagulation and acenocoumarol as an anticoagulant as opposed to warfarin had a strong negative influence on TTR, while age increased TTR. Being a man rather than a woman afforded more than three TTR points. Number of medications and average anticoagulant dose were equal between sexes.
DISCUSSION
Women have a lower TTR than men, on average below the safety threshold. They were indeed older, but age positively influenced TTR. Since women and men were equally comorbid, neither age nor disease explains differences in TTR. None of the other variables included in the study could explain the gender gap in TTR. Since women are at increased risk of cardioembolic stroke in atrial fibrillation, an effort at defining other causes for the observed differences, closer monitoring and switching to direct anticoagulants whenever possible is warranted.
Topics: Anticoagulants; Atrial Fibrillation; Comorbidity; Female; Humans; International Normalized Ratio; Male; Retrospective Studies; Stroke; Treatment Outcome; Vitamin K; Warfarin
PubMed: 33901765
DOI: 10.1016/j.thromres.2021.04.011 -
International Journal of Environmental... Feb 2021Bleeding complications in patients undergoing antiplatelet and/or anticoagulant therapy have been one of the main concerns in dental practice. Upon the introduction of...
BACKGROUND
Bleeding complications in patients undergoing antiplatelet and/or anticoagulant therapy have been one of the main concerns in dental practice. Upon the introduction of new antiplatelet and anticoagulant drugs, there is a search for new protocols that respond to a secure treatment. The aim of the present study was to evaluate bleeding complications in anticoagulated and antiplatelet-treated patients after performing simple dental extractions, in a period of 4 years.
MATERIAL AND METHODS
147 clinical records of anticoagulated and/or antiplatelet-treated patients undergoing a simple dental extraction over a period of 4 years (October 2015 to September 2019) were studied. Within the sample, 63 patients were antiplatelet-treated, 83 were anticoagulated, and 1 patient was under both therapies. Within the anticoagulated patients, 70 took classic anticoagulants and 14 new oral anticoagulants (NOACs). Quantitative data were studied with arithmetic mean and standard deviation (SD). The chi-square test was used for the qualitative variables. ANOVA tests were used to compare age and anticoagulated or antiplatelet-treated patients. Statistical significance was determined when < 0.05.
RESULTS
From the 418 dental extractions performed, five severe bleeding complications took place in three patients (2.11%). From the five events, four were in patients treated with NOACs (1.68%) and one occurred in a patient anticoagulated with acenocoumarol (0.42%; = 0.003).
CONCLUSIONS
Considering the results of this retrospective clinical study, we can conclude that bleeding complications in anticoagulated and/or antiplatelet-treated patients after tooth extractions were low, with a higher incidence recorded in patients treated with NOACs, followed by classic anticoagulants, and there were no complications in antiplatelet-treated patients.
Topics: Administration, Oral; Anticoagulants; Dental Offices; Humans; Platelet Aggregation Inhibitors; Retrospective Studies; Tooth Extraction
PubMed: 33567762
DOI: 10.3390/ijerph18041609 -
The Australasian Journal of Dermatology Aug 2019Calciphylaxis is a syndrome of cutaneous ischaemic necrosis and ulceration due to arteriolar calcification with subsequent thrombosis, which rarely presents in patients...
Calciphylaxis is a syndrome of cutaneous ischaemic necrosis and ulceration due to arteriolar calcification with subsequent thrombosis, which rarely presents in patients without terminal kidney disease. Recently, several reports of coumarins-associated calciphylaxis have stressed the relevance of anticoagulant therapy as an important risk factor for the development of this condition. We report five cases of acenocoumarol-associated, biopsy-proven calciphylaxis in women aged between 64 and 92 years. The drug had been prescribed for atrial fibrillation and was taken without interruption from 14 to 224 months. Lesions were present for months in all cases and were resistant to multiple therapeutic options, but they resolved only with simple wound care measures 6-14 months after changing the anticoagulant therapy.
Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Calciphylaxis; Deprescriptions; Female; Humans; Middle Aged
PubMed: 30790279
DOI: 10.1111/ajd.13006