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Journal of Thrombosis and Haemostasis :... May 2016The periprocedural management of patients receiving chronic therapy with oral anticoagulants (OACs), including vitamin K antagonists (VKAs) such as warfarin and direct... (Review)
Review
The periprocedural management of patients receiving chronic therapy with oral anticoagulants (OACs), including vitamin K antagonists (VKAs) such as warfarin and direct OACs (DOACs), is a common clinical problem. The optimal perioperative management of patients receiving chronic OAC therapy is anchored on four key principles: (i) risk stratification of patient-related and procedure-related risks of thrombosis and bleeding; (ii) the clinical consequences of a thrombotic or bleeding event; (iii) discontinuation and reinitiation of OAC therapy on the basis of the pharmacokinetic properties of each agent; and (iv) whether aggressive management such as the use of periprocedural heparin bridging has advantages for the prevention of postoperative thromboembolism at the cost of a possible increase in bleeding risk. Recent data from randomized trials in patients receiving VKAs undergoing pacemaker/defibrillator implantation or using heparin bridging therapy for elective procedures or surgeries can now inform best practice. There are also emerging data on periprocedural outcomes in the DOAC trials for patients with non-valvular atrial fibrillation. This review summarizes the evidence for the periprocedural management of patients receiving chronic OAC therapy, focusing on recent randomized trials and large outcome studies, to address three key clinical scenarios: (i) can OAC therapy be safely continued for minor procedures or surgeries; (ii) if therapy with VKAs (especially warfarin) needs to be temporarily interrupted for an elective procedure/surgery, is heparin bridging necessary; and (iii) what is the optimal periprocedural management of the DOACs? In answering these questions, we aim to provide updated clinical guidance for the periprocedural management of patients receiving VKA or DOAC therapy, including the use of heparin bridging.
Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Aortic Valve; Atrial Fibrillation; Elective Surgical Procedures; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Perioperative Care; Phenprocoumon; Prothrombin; Randomized Controlled Trials as Topic; Societies, Medical; Thromboembolism; Thrombosis; United States; Vitamin K; Warfarin
PubMed: 26988871
DOI: 10.1111/jth.13305 -
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 -
European Review For Medical and... Jul 2021The embolization of thrombi formed within the atria can occur in any form of atrial fibrillation (AF), i.e., paroxysmal, persistent, or permanent. Although ischemic... (Comparative Study)
Comparative Study
OBJECTIVE
The embolization of thrombi formed within the atria can occur in any form of atrial fibrillation (AF), i.e., paroxysmal, persistent, or permanent. Although ischemic stroke is the most frequent embolic event associated with AF, embolization to other sites in the pulmonary and systemic circulations may occasionally occur. To avert the risk of embolization, long-term oral anticoagulation therapy is recommended for all AF patients if the CHA2DS2-VASC score is at least 1 for men and at least 2 for women. Since anticoagulant therapy is associated with an increased risk of bleeding, the choice of oral anticoagulant agent should be made by careful consideration of the benefit-to-risk ratio. The use of a newer class of direct oral anticoagulants (DOACs) as an alternative to the anti-vitamin K (AVK) anticoagulants (warfarin, acenocumarol, etc.) can help mitigate the need for periodic monitoring of International Normalized Ratio (INR) and adverse bleeding events that are commonly associated with the use of AVK anticoagulants. Though the use of DOACs (dabigatran, rivaroxaban, edoxaban, apixaban, etc.) is gaining ground due to their relative safety profile and the low overall cost, quite a few clinicians remain skeptical about their use.
PATIENTS AND METHODS
Our objective was to evaluate the risk of thromboembolism, stroke, neuropsychiatric illness, depression, and dementia, in patients with non-valvular atrial fibrillation who have been treated with either acenocumarol or apixaban, as well as to see the inflammatory status (ESR) and levels of fibrinogen. Our team at Municipal Emergency University Hospital, Timisoara, Romania, conducted a retrospective study using the medical records of AF patients who were treated with either apixaban or acenocumarol between 2016-2019. We divided the patients into two groups and compared the groups for the aforementioned outcomes.
RESULTS
AF patients who were prescribed apixaban had a lower rate of stroke and psychiatric illness compared to those on acenocumarol. No significant correlation was found in terms of risk of developing depression or dementia between the groups.
CONCLUSIONS
Non-valvular AF patients on apixaban had lower rates of thromboembolic events than the patients on acenocumarol. This article will serve as a reminder of the positive health and financial outcomes of apixaban use, especially to those healthcare systems that are still oblivious to the decrease in economic burden and gain in quality-adjusted life years (QALY) by the long-term use of NOACS/ DOACS instead of the AVK anticoagulants.
Topics: Acenocoumarol; Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Clinical Decision-Making; Female; Hemorrhage; Humans; Incidence; International Normalized Ratio; Male; Middle Aged; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Retrospective Studies; Risk Assessment; Romania; Stroke
PubMed: 34286492
DOI: 10.26355/eurrev_202107_26241 -
Clinical and Applied... Oct 2017Chronic rheumatic heart disease (RHD) patients who undergo valve replacement with mechanical valves require lifelong anticoagulation. Acenocoumarol, a vitamin K...
BACKGROUND AND AIM
Chronic rheumatic heart disease (RHD) patients who undergo valve replacement with mechanical valves require lifelong anticoagulation. Acenocoumarol, a vitamin K antagonist has a narrow therapeutic range and wide inter-individual variability. Our aim was to investigate the influence of polymorphisms of VKORC1 and CYP2C9 genes on the mean daily dose requirement of acenocoumarol.
METHODS
205 chronic RHD patients, with mechanical heart valves and on acenocoumarol therapy, were recruited. Genotyping for VKORC1 (-1639G>A and 1173C>T) and CYP2C9 (*2 & *3 alleles) polymorphisms was done by PCR-RFLP. There was complete linkage disequilibrium between VKORC1 polymorphisms (r = 0.98, D' = 1.0, LOD = 74.02). VKORC1 genotype distribution for GG/CC, GA/CT, and AA/TT were 57.6%, 36.1%, and 6.3%, respectively. CYP2C9 genotype distribution for *1/*1, *1/*3, *1/*2, *2/*2, and *2/*3 were 78.5%, 14.1%, 6.3%, 0.5%, and 0.5%, respectively. Patients with a wild type of both VKORC1 (-1639GG and 1173CC) and CYP2C9 gene variants required higher acenocoumarol dose compared to those with mutant genotype ( P = 0.023 and P = 0.008 respectively). On combined genotype analysis, patients having a combination of wild type of VKORC1 with wild type of CYP2C9 (44.4%) required higher daily dose compared to patients bearing heterozygous VKORC1 (-1639GA & 1173CT) with wild type of CYP2C9 (30.2%, P = 0.008).
CONCLUSION
Presence of a mutant allele of VKORC1 (-1639A & 1173T) and CYP2C9 genes increased the odds of requiring a lower mean dosage of acenocoumarol. Studying the combination of genotypes in RHD patients could predict acenocoumarol dose requirement more accurately.
Topics: Acenocoumarol; Cytochrome P-450 CYP2C9; Female; Genotype; Heart Valve Prosthesis; Humans; India; Male; Polymorphism, Single Nucleotide; Rheumatic Heart Disease; Vitamin K Epoxide Reductases
PubMed: 27335128
DOI: 10.1177/1076029616655617 -
Journal of Thrombosis and Haemostasis :... Apr 2012The required acenocoumarol dose and the risk of underanticoagulation and overanticoagulation are associated with the CYP2C9 and VKORC1 genotypes. However, the duration...
BACKGROUND
The required acenocoumarol dose and the risk of underanticoagulation and overanticoagulation are associated with the CYP2C9 and VKORC1 genotypes. However, the duration of the effects of these genes on anticoagulation is not yet known.
OBJECTIVES
In the present study, the effects of these polymorphisms on the risk of underanticoagulation and overanticoagulation over time after the start of acenocoumarol were investigated.
PATIENTS/METHODS
In three cohorts, we analyzed the relationship between the CYP2C9 and VKORC1 genotypes and the incidence of subtherapeutic or supratherapeutic International Normalized Ratio (INR) values (< 2 and > 3.5) or severe overanticoagulation (INR > 6) for different time periods after treatment initiation.
RESULTS
Patients with polymorphisms in CYP2C9 and VKORC1 had a higher risk of overanticoagulation (up to 74%) and a lower risk of underanticoagulation (down to 45%) in the first month of treatment with acenocoumarol, but this effect diminished after 1-6 months.
CONCLUSIONS
Knowledge of the patient's genotype therefore might assist physicians to adjust doses in the first month(s) of therapy.
Topics: Acenocoumarol; Aged; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Blood Coagulation; Cytochrome P-450 CYP2C9; Drug Administration Schedule; Drug Dosage Calculations; Drug Monitoring; Female; Gene Frequency; Genotype; Humans; International Normalized Ratio; Male; Medication Errors; Mixed Function Oxygenases; Netherlands; Pharmacogenetics; Phenotype; Polymorphism, Genetic; Predictive Value of Tests; Risk Assessment; Risk Factors; Time Factors; Vitamin K Epoxide Reductases
PubMed: 22252093
DOI: 10.1111/j.1538-7836.2012.04633.x -
European Journal of Clinical... Dec 2016The purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs). (Clinical Trial)
Clinical Trial
PURPOSE
The purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs).
METHODS
We selected patients on VKAs of two Dutch anticoagulation clinics who initiated treatment with a statin between 2009 and 2013. Patients who initiated or stopped concomitant drugs that interact with VKAs or were hospitalised during follow-up were excluded. The VKA dosage (mg/day) after statin initiation was compared with the last VKA dosage before the statin was started. Immediate and long-term differences in VKA dosage (at 6 and 12 weeks) were calculated with a paired student t test.
RESULTS
Four hundred thirty-five phenprocoumon users (mean age 70 years, 60 % men) and 303 acenocoumarol users (mean age 69 years, 58 % men) were included. After start of statin use, the immediate phenprocoumon dosage was 0.02 mg/day (95 % CI, 0.00 to 0.03) lower. At 6 and 12 weeks, these phenprocoumon dosages were 0.03 (95 % CI, 0.01 to 0.05) and 0.07 mg/day (95 % CI, 0.04 to 0.09) lower as compared with the dosage before first statin use. In acenocoumarol users, VKA dosage was 0.04 mg/day (95%CI, 0.01 to 0.07) (immediate effect), 0.10 (95 % CI, 0.03 to 0.16) (at 6 weeks), and 0.11 mg/day (95 % CI, 0.04 to 0.18) (after 12 weeks) lower.
CONCLUSIONS
Initiation of statin treatment was associated with an immediate and long-term minor although statistically significant decrease in VKA dosage in both phenprocoumon and acenocoumarol users, which suggests that statins may have anticoagulant properties.
Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; International Normalized Ratio; Male; Middle Aged; Phenprocoumon; Vitamin K
PubMed: 27709253
DOI: 10.1007/s00228-016-2138-6 -
Hellenic Journal of Cardiology : HJC =... 2015Administration of anticoagulation is mandatory in patients with left ventricular assist devices (LVADs). Vitamin K antagonists require regular monitoring and dosage...
INTRODUCTION
Administration of anticoagulation is mandatory in patients with left ventricular assist devices (LVADs). Vitamin K antagonists require regular monitoring and dosage adjustment. Dabigatran administered in a standard dose twice daily is more convenient and achieves a stable anticoagulant effect, but its effectiveness and safety in patients with LVADs has not been investigated. The objective of the present study was to evaluate whether dabigatran can be used safely as a second-line anticoagulation option in patients with a HeartMate II (HMII) LVAD.
METHODS
The study population consisted of 7 consecutive patients with end-stage heart failure who underwent HMII implantation and sequentially received acenocoumarol and dabigatran. Occurrence of stroke, systematic embolism, device thrombosis and major or life-threatening bleeding were included in the analysis. An acute decrease in plasma hemoglobin >2 g/dL or a need for transfusion of at least 2 units of packed red blood cells (PRBC) was defined as major bleeding, while an acute decrease in plasma hemoglobin >5 g/dL, fatal, symptomatic intracranial bleed, need for transfusion of at least 4 units PRBC, or association with hypotension requiring the use of intravenous inotropic agents or surgical intervention was defined as life-threatening bleeding.
RESULTS
The duration of follow up was 1564 ± 292 days. Patients received acenocoumarol for 855 ± 246 days, followed by dabigatran for 708 ± 368 days. The rates of thromboembolic events were similar under dabigatran and acenocoumarol treatment: strokes, 0.094 vs. 0 /patient-year, p=0.36; systemic embolism, no event in either group; and device thrombosis, 0.053 vs. 0.258 events/patient-year, p=0.19, respectively. Compared to an adjusted acenocoumarol dose, the standard dabigatran dose resulted in similar rates of life-threatening bleeding, but significantly lower rates of major bleeding (0.18 vs. 0.27 bleeds/patient-years, p=0.76, and 0.047 vs. 0.547, p<0.001, for dabigatran and acenocoumarol, respectively).
CONCLUSIONS
The safe and effective use of dabigatran as a second-line anticoagulation therapy in patients with HMII seems feasible. However, these data must be confirmed in a randomized study.
Topics: Aged; Anticoagulants; Dabigatran; Female; Follow-Up Studies; Greece; Heart Failure; Heart-Assist Devices; Hemorrhage; Humans; Incidence; Male; Middle Aged; Outcome Assessment, Health Care; Postoperative Complications; Severity of Illness Index; Thromboembolism; Ventricular Dysfunction, Left
PubMed: 25701968
DOI: No ID Found -
Revista Medica de Chile Oct 2011Thromboembolic disease (TED) is the leading cause of morbidity and mortality worldwide. The hallmark of oral long-term anticoagulant therapy has been the use of vitamin... (Review)
Review
Thromboembolic disease (TED) is the leading cause of morbidity and mortality worldwide. The hallmark of oral long-term anticoagulant therapy has been the use of vitamin K antagonists, whose anticoagulant effect is exerted inhibiting vitamin K epoxide reductase. Warfarin and acenocoumarol are the most commonly used. In the last five years several new drugs for long term anticoagulation have been developed, which can inhibit single clotting factors with the purpose of improving drug therapeutic range and, ideally, minimizing bleeding risks. This review addresses the state of the art on the clinical use of inhibitors of activated factor X and thrombin.
Topics: Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Humans; Thrombin; Vitamin K
PubMed: 22286737
DOI: No ID Found -
British Journal of Clinical Pharmacology Aug 2014Adherence to the generally complex regimen of coumarin derivatives is vital in order to keep patients in the adequate International Normalized Ratio range. Patients'...
AIMS
Adherence to the generally complex regimen of coumarin derivatives is vital in order to keep patients in the adequate International Normalized Ratio range. Patients' beliefs about medicines are associated with the level of therapy adherence. Our first aim was to assess beliefs about coumarins. Secondly, we compared the beliefs about coumarins with the beliefs about other cardiovascular drugs.
METHODS
The Beliefs about Medicines Questionnaire was used to assess medication beliefs. The questionnaire was completed by new users of coumarins indicated for venous thromboembolism or atrial fibrillation. A necessity score and a concerns score were calculated for all patients. The analyses were repeated for users of antihypertensive drugs or statins (not using coumarins).
RESULTS
Three hundred and twenty patients were included in the analysis of the beliefs about coumarins. The mean necessity score was 15.3, the concerns score 12.3 and the necessity-concerns differential 3.0. Patients with venous thromboembolism (n = 71) had higher necessity scores than patients with atrial fibrillation (n = 249; 16.8 vs. 14.9, P < 0.001). The mean necessity score in 493 users of other cardiovascular drugs was 16.1, the concerns score 13.5 and the necessity-concerns differential 2.6. The necessity score was higher in chronic cardiovascular drug users (n = 192) than in new users (n = 301; 17.9 vs. 14.9, P < 0.001).
CONCLUSIONS
Coumarin users score higher on the necessity scale than on the concerns scale, which is also the case in users of other cardiovascular drugs. Patients with atrial fibrillation have a less positive attitude towards these drugs than patients with venous thromboembolism, and could therefore benefit more from specific attention.
Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Data Interpretation, Statistical; Female; Humans; International Normalized Ratio; Male; Middle Aged; Netherlands; Patient Compliance; Patient Medication Knowledge; Phenprocoumon; Surveys and Questionnaires
PubMed: 24528215
DOI: 10.1111/bcp.12346 -
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