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Journal of Thrombosis and Thrombolysis Jan 2024The role of direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) and stage 4-5 chronic kidney disease (CKD) is controversial. Electronic medical...
Cardiovascular and renal outcomes in patients with atrial fibrillation and stage 4-5 chronic kidney disease receiving direct oral anticoagulants: a multicenter retrospective cohort study.
The role of direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) and stage 4-5 chronic kidney disease (CKD) is controversial. Electronic medical records from 2012 to 2021 were retrieved for patients with AF and stage 4-5 CKD receiving oral anticoagulants. Patients were separated into those receiving DOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) or vitamin K antagonists (VKA). Primary outcomes included ischemic stroke (IS), systemic thrombosis (SE), major bleeding, gastrointestinal bleeding, hemorrhagic stroke, acute myocardial infarction, cardiovascular death, and all-cause death. Renal outcomes included eGFR declines, creatinine doubling, progression to dialysis, and major adverse kidney events (MAKE). The primary analysis was until the end of follow up and the results at 1-year and 2-year of follow ups were also assessed. 2,382 patients (DOAC = 1,047, VKA = 1,335) between 2012 and 2021 with AF and stage 4-5 CKD were identified. The mean follow-up period was 2.3 ± 2.1 years in DOCAs and 2.6 ± 2.3 years in VKA respectively. At the end of follow up, the DOAC patients had significantly decreased SE (subdistribution hazard ratio [SHR] = 0.50, 95% confidence interval [CI] = 0.34-0.73), composite of IS/SE (SHR = 0.78, 95% CI = 0.62-0.98), major bleeding (HR = 0.77, 95% CI = 0.66-0.90), hemorrhagic stroke (HR = 0.52, 95% CI = 0.36-0.76), and composite of bleeding events (SHR = 0.80, 95% CI = 0.69-0.92) compared with VKA patients. The IS efficacy outcome revealed neutral between DOAC and VKA patients (HR = 1.05, 95% CI = 0.79-1.39). In addition, DOAC patients had significantly decreased rates of eGFR decline > 50% (SHR = 0.75, 95% CI = 0.64-0.87), creatinine doubling (SHR = 0.80, 95% CI = 0.67-0.95), and MAKE (SHR = 0.81, 95% CI = 0.71-0.93). In patients with AF and stage 4-5 CKD, use of DOAC was associated with decreased rates of a composite of ischemic stroke/systemic embolism, a composite of bleeding events, and renal events compared to VKA. Efficacy and safety benefits associated with apixaban at standard doses were consistent throughout follow-up.
Topics: Humans; Atrial Fibrillation; Hemorrhagic Stroke; Retrospective Studies; Creatinine; Anticoagulants; Rivaroxaban; Hemorrhage; Kidney Failure, Chronic; Kidney; Ischemic Stroke; Stroke; Administration, Oral
PubMed: 37605063
DOI: 10.1007/s11239-023-02885-9 -
Cardiology and Therapy Mar 2024Anticoagulation therapy has undergone significant evolution, marked by the emergence of direct oral anticoagulants with distinct advantages. Despite these advancements,... (Review)
Review
Anticoagulation therapy has undergone significant evolution, marked by the emergence of direct oral anticoagulants with distinct advantages. Despite these advancements, challenges persist in managing residual thrombotic and bleeding risks, particularly among vulnerable populations. The pursuit of alternative drugs has honed in on factor XI/XIa inhibitors. This comprehensive review delves into several key aspects regarding this new target: (i) the role of factor XI in the coagulation cascade; (ii) the genetic evidence and pathophysiologic rationale supporting factor XI inhibition as a therapeutic target; (iii) an exploration of the various types of factor XI/XIa inhibitors currently under investigation; (iv) potential applications of these medications, spanning thromboprophylaxis after orthopedic surgery, stroke prevention in atrial fibrillation, secondary prevention after acute coronary syndrome, non-cardioembolic stroke, thromboprophylaxis after foreign material implantation, end-stage renal disease, and patients with cancer; and (v) an overview of ongoing studies, recent findings, and the future trajectory of research into these drugs.
PubMed: 38306010
DOI: 10.1007/s40119-024-00352-x -
Journal of the American Heart... Dec 2023Intravenous thrombolysis (IVT) is an effective stroke therapy that remains underused. Currently, the use of IVT in patients with recent direct oral anticoagulant (DOAC)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intravenous thrombolysis (IVT) is an effective stroke therapy that remains underused. Currently, the use of IVT in patients with recent direct oral anticoagulant (DOAC) intake is not recommended. In this study we aim to investigate the safety and efficacy of IVT in patients with acute ischemic stroke and recent DOAC use.
METHODS AND RESULTS
A systematic review and meta-analysis of proportions evaluating IVT with recent DOAC use was conducted. Outcomes included symptomatic intracranial hemorrhage, any intracranial hemorrhage, serious systemic bleeding, and 90-day functional independence (modified Rankin scale score 0-2). Additionally, rates were compared between patients receiving IVT using DOAC and non-DOAC by a random effect meta-analysis to calculate pooled odds ratios (OR) for each outcome. Finally, sensitivity analysis for idarucizumab, National Institutes of Health Stroke Scale, and timing of DOAC administration was completed. Fourteen studies with 247 079 patients were included (3610 in DOAC and 243 469 in non-DOAC). The rates of IVT complications in the DOAC group were 3% (95% CI, 3-4) symptomatic intracranial hemorrhage, 12% (95% CI, 7-19) any ICH, and 0.7% (95%CI, 0-1) serious systemic bleeding, and 90-day functional independence was achieved in 57% (95% CI, 43-70). The rates of symptomatic intracranial hemorrhage (3.4 versus 3.5%; OR, 0.95 [95% CI, 0.67-1.36]), any intracranial hemorrhage (17.7 versus 17.3%; OR, 1.23 [95% CI, 0.61-2.48]), serious systemic bleeding (0.7 versus 0.6%; OR, 1.27 [95% CI, 0.79-2.02]), and 90-day modified Rankin scale score 0-2 (46.4 versus 56.8%; OR, 1.21 [95% CI, 0.400-3.67]) did not differ between DOAC and non-DOAC groups. There was no difference in symptomatic intracranial hemorrhage rate based on idarucizumab administration.
CONCLUSIONS
Patients with acute ischemic stroke treated with IVT in recent DOAC versus non-DOAC use have similar rates of hemorrhagic complications and functional independence. Further prospective randomized trials are warranted.
Topics: Humans; Stroke; Fibrinolytic Agents; Ischemic Stroke; Thrombolytic Therapy; Brain Ischemia; Hemorrhage; Intracranial Hemorrhages; Treatment Outcome; Anticoagulants
PubMed: 38108256
DOI: 10.1161/JAHA.123.031669 -
Expert Opinion on Drug Metabolism &... May 2024Direct oral anticoagulants (DOAC) are the guideline-recommended therapy for prevention of stroke in atrial fibrillation (AF) and venous thromboembolism. Since... (Review)
Review
INTRODUCTION
Direct oral anticoagulants (DOAC) are the guideline-recommended therapy for prevention of stroke in atrial fibrillation (AF) and venous thromboembolism. Since approximately 10% of patients using antiepileptic drugs (AED) also receive DOAC, aim of this review is to summarize data about drug-drug interactions (DDI) of DOAC with AED by using data from PubMed until December 2023.
AREAS COVERED
Of 49 AED, only 16 have been investigated regarding DDI with DOAC by case reports or observational studies. No increased risk for stroke was reported only for topiramate, zonisamide, pregabalin, and gabapentin, whereas for the remaining 12 AED conflicting results regarding the risk for stroke and bleeding were found. Further 16 AED have the potential for pharmacodynamic or pharmacokinetic DDI, but no data regarding DOAC are available. For the remaining 17 AED it is unknown if they have DDI with DOAC.
EXPERT OPINION
Knowledge about pharmacokinetic and pharmacodynamic DDI of AED and DOAC is limited and frequently restricted to and findings. Since no data about DDI with DOAC are available for 67% of AED and an increasing number of patients have a combined medication of DOAC and AED, there is an urgent need for research on this topic.
Topics: Humans; Stroke; Anticonvulsants; Drug Interactions; Anticoagulants; Atrial Fibrillation; Administration, Oral; Secondary Prevention; Hemorrhage; Venous Thromboembolism; Primary Prevention; Animals
PubMed: 38712571
DOI: 10.1080/17425255.2024.2352466 -
The American Journal of Cardiology Sep 2023Direct oral anticoagulants (DOACs) are a favored treatment to prevent stroke in patients with atrial fibrillation (AF). There are limited data concerning the efficacy...
Direct oral anticoagulants (DOACs) are a favored treatment to prevent stroke in patients with atrial fibrillation (AF). There are limited data concerning the efficacy and safety of DOACs in obese. Obesity leads to wide structural and physiological changes that may affect the pharmacokinetics and pharmacodynamics of drugs. The optimal dosing strategies for DOACs in this significant and growing sub-group remain unknown. The study aimed to evaluate on a large scale the safety and efficacy of DOAC treatment in extreme obese patients with AF. In this retrospective cohort study, we included patients with AF treated with DOACs. Patients were divided according to body mass index (BMI). Study outcomes included stroke, major bleeding, and death. Between 2012 and 2017, 5183 patients with AF were included in the analysis (2,688, 2137, and 358 patients had a BMI <30, 30 to 40, and >40 accordingly). There was no significant difference in the prevalence of ischemic events (9.9%, 8.2%, and 7.5% of patients with BMI <30, 30 to 40, and >40, respectively, p = 0.088), major bleeding events (13%, 14.1%, and 11.2% of patients with BMI <30, 30 to 40, and >40, respectively, p value = 0.257) or net ischemic and major bleeding events (18.7%, 18.7%, and 15.4% of patients with BMI <30, 30 to 40, and >40 respectively, p = 0.297) between the BMI groups. In conclusion, DOACs treatment for prevention of ischemic events in AF is effective and safe through the BMI spectrum, including extreme obesity.
Topics: Humans; Atrial Fibrillation; Warfarin; Anticoagulants; Retrospective Studies; Stroke; Hemorrhage; Obesity; Administration, Oral
PubMed: 37473672
DOI: 10.1016/j.amjcard.2023.06.079 -
European Heart Journal. Quality of Care... Sep 2023The aim of this study was to determine the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in adults with atrial fibrillation... (Observational Study)
Observational Study
Kidney function and the comparative effectiveness and safety of direct oral anticoagulants vs. warfarin in adults with atrial fibrillation: a multicenter observational study.
AIMS
The aim of this study was to determine the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in adults with atrial fibrillation (AF) by level of kidney function.
METHODS AND RESULTS
We pooled findings from five retrospective cohorts (2011-18) across Australia and Canada of adults with; a new dispensation for a DOAC or warfarin, an AF diagnosis, and a measure of baseline estimated glomerular filtration rate (eGFR). The outcomes of interest, within 1 year from the cohort entry date, were: (1) the composite of all-cause death, first hospitalization for ischaemic stroke, or transient ischaemic attack (effectiveness), and (2) first hospitalization for major bleeding defined as an intracranial, upper or lower gastrointestinal, or other bleeding (safety). Cox models were used to examine the association of a DOAC vs. warfarin with outcomes, after 1:1 matching via a propensity score. Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. A total of 74 542 patients were included in the matched analysis. DOAC initiation was associated with greater or similar effectiveness compared with warfarin initiation across all eGFR categories [pooled HRs (95% CIs) for eGFR categories: 0.74(0.69-0.79), 0.76(0.54-1.07), 0.68(0.61-0.75) and 0.86(0.76-0.98)], respectively. DOAC initiation was associated with lower or similar risk of major bleeding than warfarin initiation [pooled HRs (95% CIs): 0.75(0.65-0.86), 0.81(0.65-1.01), 0.82(0.66-1.02), and 0.71(0.52-0.99), respectively). Associations between DOAC initiation, compared with warfarin initiation, and study outcomes were not modified by eGFR category.
CONCLUSION
DOAC use, compared with warfarin use, was associated with a lower or similar risk of all-cause death, ischaemic stroke, and transient ischaemic attack and also a lower or similar risk of major bleeding across all levels of kidney function.
Topics: Humans; Adult; Warfarin; Atrial Fibrillation; Ischemic Attack, Transient; Anticoagulants; Retrospective Studies; Brain Ischemia; Stroke; Hemorrhage; Ischemic Stroke; Kidney
PubMed: 36302143
DOI: 10.1093/ehjqcco/qcac069 -
Hypertension Research : Official... Dec 2023The benefits of direct oral anticoagulants (DOACs) and warfarin in elderly Japanese patients with non-valvular atrial fibrillation (NVAF) and high home systolic blood...
Anticoagulant therapy and home blood pressure-associated risk for stroke/bleeding events in elderly patients with non-valvular atrial fibrillation: the sub-cohort study of ANAFIE registry.
The benefits of direct oral anticoagulants (DOACs) and warfarin in elderly Japanese patients with non-valvular atrial fibrillation (NVAF) and high home systolic blood pressure (H-SBP) are unclear. This sub-cohort study of the ANAFIE Registry estimated the incidence of clinical outcomes in patients receiving anticoagulant therapy (warfarin and DOACs) stratified by H-SBP levels (<125 mmHg, ≥125-<135 mmHg, ≥135-<145 mmHg and ≥145 mmHg). Of the overall ANAFIE population, 4933 patients who underwent home blood pressure (H-BP) measurements were analyzed; 93% received OACs (DOACs: 3494, 70.8%; warfarin: 1092, 22.1%). In the warfarin group, at <125 mmHg and ≥145 mmHg, the respective incidence rates (per 100 person-years) were 1.91 and 5.89 for net cardiovascular outcome (a composite of stroke/systemic embolic events (SEE) and major bleeding), 1.31 and 3.39 for stroke/SEE, 0.59 and 3.91 for major bleeding, 0.59 and 3.43 for intracranial hemorrhage (ICH), and 4.01 and 6.24 for all-cause death. Corresponding incidence rates in the DOACs group were 1.64 and 2.65, 1.00 and 1.88, 0.78 and 1.69, 0.55 and 1.31, and 3.43 and 3.51. In warfarin-treated patients, the incidence rates of net cardiovascular outcome, stroke/SEE, major bleeding, and ICH were significantly increased at H-SBP ≥ 145 mmHg versus <125 mmHg. In the DOAC group, although there was no significant difference between H-SBP < 125 mmHg and ≥145 mmHg, the incidence rates of these events tended to increase at ≥145 mmHg. These results suggest that strict BP control guided by H-BP is required in elderly NVAF patients receiving anticoagulant therapy.
Topics: Humans; Aged; Warfarin; Atrial Fibrillation; Cohort Studies; Blood Pressure; Risk Factors; Administration, Oral; Anticoagulants; Stroke; Hemorrhage; Registries
PubMed: 37433904
DOI: 10.1038/s41440-023-01361-4 -
Cardiovascular Drugs and Therapy Dec 2023The purpose of this meta-analysis was to compare efficacy and safety of direct oral anticoagulants (DOACs) to warfarin for secondary stroke prevention among adult... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of this meta-analysis was to compare efficacy and safety of direct oral anticoagulants (DOACs) to warfarin for secondary stroke prevention among adult patients with atrial fibrillation and prior stroke.
METHODS
Major repositories were screened for randomized controlled trials (RCTs), RCT subgroups, and observational studies (OBSs, divided in claims and non-claims). Occurrences of ischemic stroke or transient ischemic attack, systemic embolism, all-cause mortality, intracranial hemorrhage (ICH), and major bleeding were outcomes of interest. Hazard ratios (HRs) and their confidence intervals (95%CIs) were pooled using random-effects models for each study design. Claims studies were analyzed separately from non-claims, while RCT subgroups were grouped with OBSs (non-claims) as the randomization was broken.
RESULTS
Of 8647 articles, 20 were included (one RCT, six RCT subgroups, nine claims, and four non-claims). Comparing DOACs to warfarin, pooled HRs (95%CI) were consistently in favor of DOACs although some did not reach statistical significance: for ischemic stroke, 0.84 (0.66-1.07) in claims; 0.90 (0.77-1.06) in non-claims and RCT subgroups; for systemic embolism, 0.77 (0.62-0.96) in claims; 0.86 (0.77-0.96) in non-claims and RCT subgroups; for all-cause mortality, 0.57 (0.33-0.99) in claims; 0.87 (0.79-0.96) in non-claims and RCT subgroups; for ICH, 0.72 (0.39-1.33) in claims; 0.51 (0.38-0.67) in non-claims and RCT subgroups; and for major bleeding, 0.86 (0.71-1.03) in claims; 0.90 (0.76-1.08) for non-claims and RCT subgroups.
CONCLUSION
DOACs were associated with better efficacy and safety profiles than warfarin in atrial fibrillation patients with prior stroke, more specifically a lower risk of systemic embolism, all-cause mortality, and ICH.
Topics: Humans; Warfarin; Atrial Fibrillation; Anticoagulants; Treatment Outcome; Stroke; Hemorrhage; Intracranial Hemorrhages; Embolism; Ischemic Stroke; Administration, Oral
PubMed: 35467313
DOI: 10.1007/s10557-022-07336-w -
American Journal of Ophthalmology Case... Mar 2024To describe a case of retinal vaso-occlusive vasculitis with associated lid edema and conjunctivitis following intravitreal pegcetacoplan administration in a patient...
PURPOSE
To describe a case of retinal vaso-occlusive vasculitis with associated lid edema and conjunctivitis following intravitreal pegcetacoplan administration in a patient with geographic atrophy (GA).
OBSERVATION
A 78 year old Caucasian woman presented with complaints of lid edema, conjunctival injection, loss of vision, and mild ocular discomfort eleven days after receiving an intravitreal pegcetacoplan injection in the left eye for geographic atrophy. Visual acuity on presentation was decreased to 20/400 from 20/200 previously in that eye. Eyelid edema and conjunctival injection were present with minimal anterior chamber reaction. Dilated fundus examination revealed hemorrhages throughout the retina and signs of retinal vasculitis. The patient subsequently developed hyphema and vitreous hemorrhage. Laboratory evaluations for common infectious and inflammatory causes including aqueous and vitreous cultures for bacteria and Herpes simplex PCR were normal or negative. A delayed hypersensitivity to pegcetacoplan was suspected and was treated with topical, oral subconjunctival and intravitreal steroids.
CONCLUSION
This index report illustrates a case of retinal vaso-occlusive vasculitis associated with intravitreal pegcetacoplan associated with lid edema and conjunctival injection and subsequent hyphema and vitreous hemorrhage. Therapy with steroids topically, systemically, periocularly and intravitreally were used to treat the inflammatory process and prevent further visual loss.
PubMed: 38298266
DOI: 10.1016/j.ajoc.2024.101999 -
BMJ Case Reports Sep 2023An adolescent was referred to the emergency department due to abnormal uterine haemorrhages in the previous 2 months, associated with dizziness in the last month. At...
An adolescent was referred to the emergency department due to abnormal uterine haemorrhages in the previous 2 months, associated with dizziness in the last month. At observation, she was haemodynamically stable, with good clinical impression, but evident mucocutaneous pallor. Full blood count confirmed a severe anaemia (haemoglobin 47 g/L). She received red blood cell transfusion (10 mL/kg) and started oral oestradiol. She was discharged, with oral oestradiol and oral iron supplementation. Two weeks later, she started treatment with oestradiol and progestin. The patient had a good recovery, without new similar episodes.
Topics: Adolescent; Female; Humans; Uterine Hemorrhage; Estradiol; Dizziness; Emergency Service, Hospital; Erythrocyte Transfusion
PubMed: 37723096
DOI: 10.1136/bcr-2023-255501