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1.
J Stroke Cerebrovasc Dis ; : 107839, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944363

RESUMO

INTRODUCTION: -Patients with atrial fibrillation (AF) undergoing elective procedures are at risk for Major Adverse Cardiovascular Events (MACE) and symptomatic bleeding. We aimed to identify risk factors to guide perioperative risk stratification. METHODS: -We conducted a post-hoc analysis of the "Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery" randomized trial. The primary outcomes were MACE and symptomatic bleeding. Our statistical approach encompassed standard univariate analysis, logistic stepwise regression, and Cox regression models. Additional interaction analyses evaluated the interplay between low-molecular-weight heparin bridge therapy and other identified risk factors. RESULTS: -Among A total of 1,813 participants (mean age 71.6±8.8, 73.3% male), MACE occurred in 25 (1.4%) individuals, with pre-procedure clopidogrel use (adjusted hazard ratio [aHR] 7.73, 95% CI 2.63-22.72, p<0.001) and CHA2DS2-VASc score ≥ 5 (aHR 2.89, 95% CI 1.26-6.63, p=0.012) identified as risk factors. Symptomatic bleeding occurred in 57 (3.1%) individuals, with bridge therapy (aHR 1.84, 95% CI 1.07-3.19, p=0.029), renal disease (aHR 2.50, 95% CI 1.34-4.67, p=0.004), post-procedure aspirin use (aHR 2.86, 95% CI 1.66-4.91, p<0.001), post-procedure nonsteroidal anti-inflammatory drug use excluding aspirin (aHR 3.40, 95% CI 1.22-9.43, p=0.019), and major surgery (aHR 3.94, 95% CI 2.26-6.85, p<0.001) identified as risk factors. The interactions between risk factors and bridging therapy on MACE and symptomatic bleeding outcomes were not significant (p>0.05). CONCLUSION: -We identified predictors for MACE and symptomatic bleeding in AF patients undergoing elective procedures. These insights may help guide perioperative decisions to reduce the risk of adverse outcomes.

2.
J Thromb Haemost ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38729576

RESUMO

BACKGROUND: No study has investigated the perioperative management and clinical outcomes in patients who are receiving rivaroxaban 2.5 mg twice a day and acetylsalicylic acid (ASA) 81 to 100 mg daily. OBJECTIVE: To assess perioperative management and outcomes in patients who are receiving low-dose rivaroxaban, 2.5 mg twice-daily, and low-dose ASA, 81 to 100 mg daily. To assess perioperative management and outcomes in patients who are receiving low-dose rivaroxaban, 2.5 mg twice-daily, and low-dose ASA, 81 to 100 mg daily. METHODS: Subanalysis of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial was performed to assess perioperative management and clinical outcomes in patients with stable coronary or peripheral artery disease who were randomized to receive rivaroxaban 2.5 mg twice a day plus ASA 100 mg daily, rivaroxaban 5 mg twice a day, or ASA 100 mg daily. Patients studied required a surgery/procedure during the trial. The study outcomes, which included myocardial infarction, angina, stroke, acute limb ischemia, bleeding, and death, were assessed according to treatment allocation. RESULTS: There were 2632 patients studied (mean age, 68 years; 80% male) who had a surgery/procedure, comprising percutaneous coronary interventions (∼43%), carotid or other arterial angioplasty (∼15%), pacemaker or internal cardiac defibrillator implantation (∼9%), and coronary artery bypass graft surgery (∼7%). Perioperative study drug management varied, with about one-third of patients not interrupting study drug and the remainder interrupting it between 1 and ≥10 days preprocedure. The incidences of adverse outcomes across treatment groups were 12.7% to 15.3% for myocardial ischemia, 0.8% to 1.2% for stroke, 0.1% to 0.2% for venous thromboembolism, and 3.1% to 4.2% for any bleeding. There was no statistically significant difference in outcome rates across treatment groups. CONCLUSION: In patients in the COMPASS trial who required a surgery/procedure, there was no significant difference in perioperative adverse outcomes whether patients were receiving rivaroxaban 2.5 mg twice a day and ASA 100 mg daily, rivaroxaban 5 mg twice a day, or ASA alone.

3.
Ann Intern Med ; 177(1): JC11, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38163369

RESUMO

SOURCE CITATION: Villiger R, Juillard P, Darbellay Farhoumand P, et al. Prediction of in-hospital bleeding in acutely ill medical patients: external validation of the IMPROVE bleeding risk score. Thromb Res. 2023;230:37-44. 37634309.


Assuntos
Hemorragia , Pacientes Internados , Humanos , Fatores de Risco , Hospitais
5.
J Thromb Haemost ; 22(3): 727-737, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37949316

RESUMO

BACKGROUND: Cancer and atrial fibrillation (AF) are common concurrent disorders. Direct oral anticoagulants (DOACs) are prescribed to prevent stroke in patients with AF. Patients with cancer often undergo invasive procedures for diagnostic or therapeutic purposes, necessitating interruption of anticoagulation. There are limited data to guide best periprocedural anticoagulation management practices in the setting of active cancer. OBJECTIVES: To describe patient characteristics, periprocedural management, and clinical outcomes in DOAC-treated patients with AF according to active cancer status. METHODS: We conducted descriptive and comparative analyses using data from the PAUSE study. Multivariable logistic regression was used to determine whether active cancer status was an independent risk factor for bleeding outcomes. Covariates were selected a priori based on biological rationale and preexisting knowledge. RESULTS: Patients with active cancer were older (P < .001), more likely to be thrombocytopenic (P = .026), have moderate renal dysfunction (P = .005), and more likely to receive low-dose DOAC therapy (P < .001). A greater proportion of patients with active cancer underwent a high-bleed-risk procedure (P < .001), with longer periprocedural DOAC-interruption intervals (P <.001) and lower preprocedural residual DOAC levels (P = .002). Active cancer was an independent predictor for surgical major bleeding (OR = 2.45; 95% CI, 1.08-5.14) after adjusting for study center, procedure category and bleed risk, thrombocytopenia, hypertension, and the use of a P2Y12 inhibitor. CONCLUSIONS: Active cancer status is associated with an increased risk of surgical major bleeding among DOAC-treated patients with AF undergoing interruption of anticoagulation for elective invasive procedures.


Assuntos
Fibrilação Atrial , Neoplasias , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Anticoagulantes/uso terapêutico , Hemorragia/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/diagnóstico , Coagulação Sanguínea , Administração Oral , Neoplasias/complicações , Neoplasias/tratamento farmacológico
6.
Res Pract Thromb Haemost ; 7(3): 100137, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37122531

RESUMO

Background: Direct oral anticoagulants (DOACs) are widely used in patients with atrial fibrillation and venous thromboembolism. However, DOACs have important potential drug-drug interactions (DDIs) with several classes of drugs. In particular, antiepileptic (AE) drugs may induce cytochrome P450 3A4 or P-glycoprotein. Co-administration of DOACs and AE drugs may result in lower DOAC drug levels and reduced DOAC efficacy. However, the clinical significance of such DDIs is uncertain. Objectives: The aim of this systematic review was to generate an updated review of these DDIs and their clinical relevance, given the rapidly evolving knowledge relating to DOAC and AE DDIs. Methods: We searched the MEDLINE and Embase databases for studies reporting clinical adverse outcomes (thrombotic events, bleeding events, and all-cause mortality) in patients concomitantly taking DOACs and AE drugs. Results: We retrieved 874 studies of which 15 were deemed eligible for this review, including 4 congress abstracts, 3 case reports, 2 letters to the editor, 5 retrospective cohorts, and 1 prospective cohort study. No randomized clinical trials were found. Most of the included studies reported thrombotic events, 3 studies reported major bleeding, and one study reported all-cause mortality associated with DOAC and AE drug administration. Substantial differences in the study designs did not allow for a meta-analysis to be performed. Conclusion: The current literature assessing these adverse clinical outcomes from DOAC and AE drug co-administration is limited. Although the available data point to a possible increased risk of thrombotic events, they are insufficient to draw definitive conclusions. Well-designed clinical studies are of utmost importance.

8.
Chest ; 163(5): 1245-1257, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36462533

RESUMO

BACKGROUND: The management of patients who are receiving chronic oral anticoagulation therapy and require an elective surgery or an invasive procedure is a common clinical scenario. RESEARCH QUESTION: What is the best available evidence to support the development of American College of Chest Physicians guidelines on the perioperative management of patients who are receiving long-term vitamin K agonist (VKA) or direct oral anticoagulant (DOAC) and require elective surgery or procedures? STUDY DESIGN AND METHODS: A literature search including multiple databases from database inception through July 16, 2020, was performed. Meta-analyses were conducted when appropriate. RESULTS: In patients receiving VKA (warfarin) undergoing elective noncardiac surgery, shorter (< 3 days) VKA interruption is associated with an increased risk of major bleeding. In patients who required VKA interruption, heparin bridging (mostly with low-molecular-weight heparin [LMWH]) was associated with a statistically significant increased risk of major bleed, representing a very low certainty of evidence (COE). Compared with DOAC interruption 1 to 4 days before surgery, continuing DOACs may be associated with higher risk of bleeding demonstrated in some, but not all studies. In patients who needed DOAC interruption, bridging with LMWH may be associated with a statistically significant increased risk of bleeding, representing a low COE. INTERPRETATION: The certainty in the evidence supporting the perioperative management of anticoagulants remains limited. No high-quality evidence exists to support the practice of heparin bridging during the interruption of VKA or DOAC therapy for an elective surgery or procedure, or for the practice of interrupting VKA therapy for minor procedures, including cardiac device implantation, or continuation of a DOAC vs short-term interruption of a DOAC in the perioperative period.


Assuntos
Anticoagulantes , Heparina de Baixo Peso Molecular , Humanos , Heparina de Baixo Peso Molecular/uso terapêutico , Anticoagulantes/uso terapêutico , Heparina , Varfarina , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Vitamina K , Administração Oral
9.
NEJM Evid ; 2(6): EVIDra2200322, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38320132

RESUMO

Anticoagulant and Antiplatelet Drug ManagementManagement of patients on an anticoagulant or antiplatelet drug who require surgery or an invasive procedure is a common clinical problem. Douketis and Spyropoulos provide an evidence-based but practical approach to managing anticoagulants and antiplatelet drugs in the perioperative setting.


Assuntos
Anticoagulantes , Inibidores da Agregação Plaquetária , Humanos , Assistência Perioperatória/métodos , Serviços de Saúde
10.
Chest ; 162(5): 207-243, 20221101.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-1415023

RESUMO

The American College of Chest Physicians Clinical Practice Guideline on the Perioperative Management of Antithrombotic Therapy addresses 43 Patients-Interventions-Comparators-Outcomes (PICO) questions related to the perioperative management of patients who are receiving long-term oral anticoagulant or antiplatelet therapy and require an elective surgery/procedure. This guideline is separated into four broad categories, encompassing the management of patients who are receiving: (1) a vitamin K antagonist (VKA), mainly warfarin; (2) if receiving a VKA, the use of perioperative heparin bridging, typically with a low-molecular-weight heparin; (3) a direct oral anticoagulant (DOAC); and (4) an antiplatelet drug. Strong or conditional practice recommendations are generated based on high, moderate, low, and very low certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for clinical practice guidelines. A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation; and (2) continuation of VKA therapy in patients having a pacemaker or internal cardiac defibrillator implantation. There are separate recommendations on the perioperative management of patients who are undergoing minor procedures, comprising dental, dermatologic, ophthalmologic, pacemaker/internal cardiac defibrillator implantation, and GI (endoscopic) procedures. Substantial new evidence has emerged since the 2012 iteration of these guidelines, especially to inform best practices for the perioperative management of patients who are receiving a VKA and may require heparin bridging, for the perioperative management of patients who are receiving a DOAC, and for patients who are receiving one or more antiplatelet drugs. Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management


Assuntos
Humanos , Trombose/tratamento farmacológico , Procedimentos Cirúrgicos Eletivos , Assistência Perioperatória/normas , Fibrinolíticos/uso terapêutico
11.
J Thromb Haemost ; 20(12): 2953-2963, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36200348

RESUMO

BACKGROUND: The Perioperative Anticoagulation Use for Surgery Evaluation study prospectively evaluated a prespecified periprocedural interruption strategy of direct oral anticoagulants (DOACs) among patients with atrial fibrillation. Coagulation testing is widely available and frequently requested prior to invasive procedures. Coagulation assays display poor sensitivity to clinically relevant DOAC concentrations. OBJECTIVES: Determine the utility of routinely available coagulation testing at predicting a DOAC concentration of <30 ng/ml among patients in the preprocedural setting. METHODS: We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratio (LR+ and LR-) of a normal coagulation assay result for identifying patients with a preprocedural DOAC level < 30 ng/ml. RESULTS: We identified weak or very weak correlations between coagulation assay results and DOAC levels in the preprocedural setting, except for a moderate correlation between the thrombin time (TT) and dabigatran concentrations (ρ = 0.68; p < .001). The prothrombin time (PT) and activated partial thromboplastin time (APTT) demonstrated modest sensitivity (78.9% to 88.2%) and PPVs (76.4% to 93.1%) but poor specificity (13.2% to 53.3%) and NPVs (16.3% to 30.2%) across all three DOACs. A normal TT was associated with 100% specificity and PPV values for a dabigatran level < 30 ng/ml. A normal APTT among patients on dabigatran was associated with an LR+ of 1.671 (95% confidence interval [CI] 1.297, 2.154) and an LR- of 0.395 (95% CI 0.207, 0.751) for levels <30 ng/ml. CONCLUSIONS: The PT and APTT perform poorly at safely identifying patients with negligible DOAC levels in the preprocedural setting.


Assuntos
Dabigatrana , Rivaroxabana , Humanos , Piridonas , Pirazóis , Testes de Coagulação Sanguínea/métodos , Anticoagulantes/uso terapêutico , Tempo de Tromboplastina Parcial , Administração Oral
12.
Mayo Clin Proc Innov Qual Outcomes ; 6(6): 564-573, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36304523

RESUMO

Objective: To summarize the available evidence about the perioperative management of patients who are receiving long-term antiplatelet therapy and require elective surgery/procedures. Methods: This systematic review supports the development of the American College of Chest Physicians guideline on the perioperative management of antiplatelet therapy. A literature search of MEDLINE, EMBASE, Scopus and Cochrane databases was conducted from each database's inception to July 16, 2020. Meta-analyses were conducted when possible. Results: In patients receiving long-term antiplatelet therapy and undergoing elective noncardiac surgery, the available evidence did not show a significant difference in major bleeding between a shorter vs longer antiplatelet interruption, with low certainty of evidence (COE). Compared with patients who received placebo perioperatively, aspirin continuation was associated with increased risk of major bleeding (relative risk [RR], 1.31; 95% CI, 1.15-1.50; high COE) and lower risk of major thromboembolism (RR, 0.74; 95% CI, 0.58-0.94; moderate COE). During antiplatelet interruption, bridging with low-molecular-weight heparin was associated with increased risk of major bleeding compared with no bridging (RR, 1.86; 95% CI, 1.24-2.79; very low COE). Continuation of antiplatelets during minor dental and ophthalmologic procedures was not associated with a statistically significant difference in the risk of major bleeding (very low COE). Conclusion: This systematic review summarizes the current evidence about the perioperative management of antiplatelet therapy and highlights the urgent need for further research, particularly with the increasing prevalence of patients taking 1 or more antiplatelet agents.

13.
Chest ; 162(5): 1127-1139, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35964703

RESUMO

BACKGROUND: The American College of Chest Physicians Clinical Practice Guideline on the Perioperative Management of Antithrombotic Therapy addresses 43 Patients-Interventions-Comparators-Outcomes (PICO) questions related to the perioperative management of patients who are receiving long-term oral anticoagulant or antiplatelet therapy and require an elective surgery/procedure. This guideline is separated into four broad categories, encompassing the management of patients who are receiving: (1) a vitamin K antagonist (VKA), mainly warfarin; (2) if receiving a VKA, the use of perioperative heparin bridging, typically with a low-molecular-weight heparin; (3) a direct oral anticoagulant (DOAC); and (4) an antiplatelet drug. METHODS: Strong or conditional practice recommendations are generated based on high, moderate, low, and very low certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for clinical practice guidelines. RESULTS: A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation; and (2) continuation of VKA therapy in patients having a pacemaker or internal cardiac defibrillator implantation. There are separate recommendations on the perioperative management of patients who are undergoing minor procedures, comprising dental, dermatologic, ophthalmologic, pacemaker/internal cardiac defibrillator implantation, and GI (endoscopic) procedures. CONCLUSIONS: Substantial new evidence has emerged since the 2012 iteration of these guidelines, especially to inform best practices for the perioperative management of patients who are receiving a VKA and may require heparin bridging, for the perioperative management of patients who are receiving a DOAC, and for patients who are receiving one or more antiplatelet drugs. Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management questions.


Assuntos
Fibrinolíticos , Médicos , Humanos , Fibrinolíticos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Anticoagulantes/efeitos adversos , Heparina/efeitos adversos
14.
Chest ; 162(5): e207-e243, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35964704

RESUMO

BACKGROUND: The American College of Chest Physicians Clinical Practice Guideline on the Perioperative Management of Antithrombotic Therapy addresses 43 Patients-Interventions-Comparators-Outcomes (PICO) questions related to the perioperative management of patients who are receiving long-term oral anticoagulant or antiplatelet therapy and require an elective surgery/procedure. This guideline is separated into four broad categories, encompassing the management of patients who are receiving: (1) a vitamin K antagonist (VKA), mainly warfarin; (2) if receiving a VKA, the use of perioperative heparin bridging, typically with a low-molecular-weight heparin; (3) a direct oral anticoagulant (DOAC); and (4) an antiplatelet drug. METHODS: Strong or conditional practice recommendations are generated based on high, moderate, low, and very low certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology for clinical practice guidelines. RESULTS: A multidisciplinary panel generated 44 guideline recommendations for the perioperative management of VKAs, heparin bridging, DOACs, and antiplatelet drugs, of which two are strong recommendations: (1) against the use of heparin bridging in patients with atrial fibrillation; and (2) continuation of VKA therapy in patients having a pacemaker or internal cardiac defibrillator implantation. There are separate recommendations on the perioperative management of patients who are undergoing minor procedures, comprising dental, dermatologic, ophthalmologic, pacemaker/internal cardiac defibrillator implantation, and GI (endoscopic) procedures. CONCLUSIONS: Substantial new evidence has emerged since the 2012 iteration of these guidelines, especially to inform best practices for the perioperative management of patients who are receiving a VKA and may require heparin bridging, for the perioperative management of patients who are receiving a DOAC, and for patients who are receiving one or more antiplatelet drugs. Despite this new knowledge, uncertainty remains as to best practices for the majority of perioperative management questions.


Assuntos
Fibrinolíticos , Médicos , Humanos , Fibrinolíticos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Anticoagulantes/efeitos adversos , Heparina/efeitos adversos
15.
J Thromb Haemost ; 20(10): 2226-2236, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35906715

RESUMO

Despite the emergence of high quality randomized trial data with the use of antithrombotic agents to reduce the risk of thromboembolism, end-organ failure, and possibly mortality in patients with coronavirus disease 2019 (COVID-19), questions still remain as to optimal patient selection for these strategies, the use of antithrombotics in outpatient settings and in-hospital settings (including critical care units), thromboprophylaxis in special patient populations, and the management of acute thrombosis in hospitalized COVID-19 patients. In October 2021, the International Society on Thrombosis and Haemostasis (ISTH) formed a multidisciplinary and international panel of content experts, two patient representatives, and a methodologist to develop recommendations on treatment with anticoagulants and antiplatelet agents for COVID-19 patients. The ISTH Guideline panel discussed additional topics to be well suited to a non-Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for Good Practice Statements (GPS) to support good clinical care in the antithrombotic management of COVID-19 patients in various clinical settings. The GPS panel agreed on 17 GPS: 3 in the outpatient (pre-hospital) setting, 12 in the hospital setting both in non-critical care (ward) as well as intensive care unit settings, and 2 in the immediate post-hospital discharge setting based on limited evidence or expert opinion that supports net clinical benefit in enacting the statements provided. The antithrombotic therapies discussed in these GPS should be available in low- and middle-income countries.


Assuntos
Tratamento Farmacológico da COVID-19 , Fibrinolíticos , Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Hemostasia , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Tromboembolia Venosa/prevenção & controle
16.
Clin Transl Sci ; 15(7): 1687-1697, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35439353

RESUMO

Apixaban is frequently used off-label in transplant recipients. However, a potential drug interaction exists with the calcineurin inhibitors. We conducted an open-label drug-drug interaction study to determine the pharmacokinetics of apixaban in lung and kidney transplant recipients who were taking a calcineurin inhibitor. A single dose of apixaban 10 mg was administered orally to kidney and lung transplant recipients maintained on either tacrolimus or cyclosporine, and pharmacokinetic parameters were compared to a reference cohort of 12 healthy subjects who used the same apixaban dose and pharmacokinetic blood sampling. Fourteen participants were enrolled (n = 6 kidney, n = 8 lung), with 10 maintained on tacrolimus and four on cyclosporine. Data from 13 participants was usable. Participants were taking triple therapy immunosuppression and had a mean (SD) of 12 (3) medications. Participants receiving tacrolimus and cyclosporine had area under the plasma concentration-time curve from time zero to infinity (AUC0-inf ) geometric least square means (90% confidence interval [CI]) of 4312 (95% CI 3682, 5049) and 5388 (95% CI 3277, 8858), respectively. Compared to healthy subjects, the associated geometric mean ratios (GMRs) for apixaban maximum plasma concentration (Cmax ), AUC from time zero to the last quantifiable concentration (AUC0-tlast ) and AUC0-inf were 197% (95% CI 153, 295), 244% (95% CI 184, 323), and 224% (95% CI 170, 295) for transplant recipients on tacrolimus. The GMR (90% CI) Cmax , AUC0-tlast , and AUC0-inf of apixaban for patients on cyclosporine were 256% (95% CI 184, 358), 287% (95% CI 198, 415), and 280% (95% CI 195, 401). Kidney and lung transplant recipients receiving tacrolimus had higher apixaban exposure. A similar trend was noted for patients receiving cyclosporine, but additional patients are needed to confirm this interaction. Future studies are needed before apixaban can be safely recommended in this population, and the impact of dose staggering should be investigated. This study highlights the importance of pharmacokinetic studies in actual patient populations.


Assuntos
Ciclosporina , Tacrolimo , Inibidores de Calcineurina/efeitos adversos , Interações Medicamentosas , Humanos , Imunossupressores/efeitos adversos , Rim , Pulmão , Pirazóis , Piridonas , Transplantados
17.
Res Pract Thromb Haemost ; 6(2): e12650, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35224414

RESUMO

BACKGROUND: Carbamazepine and phenytoin are potent inducers of enzymes that metabolize oral anticoagulants. OBJECTIVES: To determine the clinical impact of drug-drug interactions between these anticonvulsants and oral anticoagulants, and whether they affect the treatment with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). MATERIAL AND METHODS: Data on patients cotreated with carbamazepine or phenytoin and an oral anticoagulant were retrospectively retrieved from medical records from 2011 to 2020. Outcomes were time in therapeutic range (TTR), DOAC levels, thromboembolic events, major bleeding, and all-cause mortality. RESULTS: Among 85 patients (37% female, median age 68 years) treated with carbamazepine (n = 43 [51%]) or phenytoin (n = 42 [49%]), 53 (62%) were initially treated with VKAs and 32 (38%) with DOACs. TTR in VKA patients was 63%, which improved in year 2. Four of seven trough and five of 12 peak DOAC plasma levels were lower than expected. The incidence rate (95% confidence interval) per 100 person-years for thromboembolism was 3.6 (3.1-4.2) for VKA patients and 4.4 (3.5-5.6) for DOAC patients; for major bleeding 1.8 (1.5-2.1) and 1.5 (1.2-1.9), and for all-cause mortality 3.6 (3.1-4.2) and 1.5 (1.2-1.9), respectively. Incidence rates between VKAs and DOACs and between carbamazepine and phenytoin were similar. CONCLUSION: There was a high incidence of thromboembolism in patients cotreated with anticoagulants and carbamazepine or phenytoin. The incidence rates of thrombotic and bleeding events were similar between VKA and DOAC patients. DOAC levels were lower than expected in 47% of cases tested, without correlation with clinical outcomes.

20.
Postgrad Med ; 133(sup1): 20-26, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33779472

RESUMO

Orthopedic surgery and surgery for cancer are major risk factors for venous thromboembolism (VTE). Deep vein thrombosis (DVT) can occur in up to 50% of patients after major orthopedic surgery. The rate of VTE after cancer surgery varies according to the type of surgery, with rates as high as those after orthopedic surgery in certain settings. Use of thromboprophylaxis in these high-risk settings is well established and recent studies inform the type and duration of thromboprophylaxis. With major orthopedic surgery, there has been a shift from use of low molecular weight heparins (LMWHs) to direct oral anticoagulants (DOACs) along with renewed interest in aspirin as a thromboprophylaxis agent. Recent studies have also informed optimal thromboprophylaxis strategies after nonmajor orthopedic surgery. Use of thromboprophylaxis after major cancer surgery for cancer is established and recent evidence has focused on the potential benefits of extended-duration thromboprophylaxis. This review will summarize emerging evidence for thromboprophylaxis after orthopedic and cancer surgery with a view to providing clinicians with concise and actionable guidance for best practice.


Assuntos
Anticoagulantes/uso terapêutico , Quimioprevenção/métodos , Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Oncologia Cirúrgica/métodos , Tromboembolia Venosa , Humanos , Complicações Pós-Operatórias/etiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
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