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Circulation Jan 2024There is ambiguity whether frail patients with atrial fibrillation managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety of Switching From a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial.
BACKGROUND
There is ambiguity whether frail patients with atrial fibrillation managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC).
METHODS
We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older patients with atrial fibrillation living with frailty (≥75 years of age plus a Groningen Frailty Indicator score ≥3) were randomly assigned to switch from international normalized ratio-guided VKA treatment to an NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mL·min·1.73 m or with valvular atrial fibrillation were excluded. Follow-up was 12 months. The cause-specific hazard ratio was calculated for occurrence of the primary outcome that was a major or clinically relevant nonmajor bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events.
RESULTS
Between January 2018 and June 2022, a total of 2621 patients were screened for eligibility and 1330 patients were randomly assigned (mean age 83 years, median Groningen Frailty Indicator score 4). After randomization, 6 patients in the switch-to-NOAC arm and 1 patient in the continue-with-VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to an NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The hazard ratio for our primary outcome was 1.69 (95% CI, 1.23-2.32). The hazard ratio for thromboembolic events was 1.26 (95% CI, 0.60-2.61).
CONCLUSIONS
Switching international normalized ratio-guided VKA treatment to an NOAC in frail older patients with atrial fibrillation was associated with more bleeding complications compared with continuing VKA treatment, without an associated reduction in thromboembolic complications.
REGISTRATION
URL: https://eudract.ema.europa.eu; Unique identifier: 2017-000393-11. URL: https://eudract.ema.europa.eu; Unique identifier: 6721 (FRAIL-AF study).
Topics: Humans; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Frail Elderly; Frailty; Thromboembolism; Vitamin K; Administration, Oral; Stroke
PubMed: 37634130
DOI: 10.1161/CIRCULATIONAHA.123.066485 -
Hematology. American Society of... Nov 2018Many drugs have been implicated in drug-induced immune thrombocytopenia (DITP). Patients with DITP develop a drop in platelet count 5 to 10 days after drug... (Review)
Review
Many drugs have been implicated in drug-induced immune thrombocytopenia (DITP). Patients with DITP develop a drop in platelet count 5 to 10 days after drug administration with an increased risk of hemorrhage. The diagnosis of DITP is often challenging, because most hospitalized patients are taking multiple medications and have comorbidities that can also cause thrombocytopenia. Specialized laboratory diagnostic tests have been developed and are helpful to confirm the diagnosis. Treatment of DITP involves discontinuation of the offending drug. The platelet count usually starts to recover after 4 or 5 half-lives of the responsible drug or drug metabolite. High doses of intravenous immunoglobulin can be given to patients with severe thrombocytopenia and bleeding. Although in most cases, DITP is associated with bleeding, life-threatening thromboembolic complications are common in patients with heparin-induced thrombocytopenia (HIT). Binding of antiplatelet factor 4/heparin antibodies to Fc receptors on platelets and monocytes causes intravascular cellular activation, leading to an intensely prothrombotic state in HIT. The clinical symptoms include a decrease in platelet counts by >50% and/or new thromboembolic complications. Two approaches can help to confirm or rule out HIT: assessment of the clinical presentation using scoring systems and in vitro demonstration of antiplatelet factor 4/heparin antibodies. The cornerstone of HIT management is immediate discontinuation of heparin when the disease is suspected and anticoagulation using nonheparin anticoagulant. In this review, we will provide an update on the pathophysiology, diagnosis, and management of both DITP and HIT.
Topics: Hemorrhage; Heparin; Humans; Immunoglobulins, Intravenous; Severity of Illness Index; Thrombocytopenia; Thromboembolism
PubMed: 30504360
DOI: 10.1182/asheducation-2018.1.576 -
Cleveland Clinic Journal of Medicine Dec 2017Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism, is a common cardiovascular disease associated with significant morbidity... (Review)
Review
Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism, is a common cardiovascular disease associated with significant morbidity ranging from painful leg swelling, chest pain, shortness of breath, and even death. Long-term complications include recurrent VTE, postpulmonary embolism syndrome, chronic thromboembolic pulmonary hypertension, and postthrombotic syndrome (PTS). Management of VTE requires immediate anticoagulation therapy based on a risk assessment for bleeding. Direct oral anticoagulants (DOACs) have become an important option for patients as reflected in the most recent American College of Chest Physician treatment guidelines.
Topics: Anticoagulants; Humans; Venous Thromboembolism
PubMed: 29257737
DOI: 10.3949/ccjm.84.s3.04 -
Clinical Journal of the American... Mar 2012After infections, thromboembolism is considered by many experts to be the most significant life-threatening complication of nephrotic syndrome. The purpose of this... (Review)
Review
After infections, thromboembolism is considered by many experts to be the most significant life-threatening complication of nephrotic syndrome. The purpose of this review is to summarize the epidemiology, clinical and molecular pathophysiology, and management of this complication. Children (2.8%) are less likely than adults (26.7%) with nephrotic syndrome to develop thromboembolism. However, infants and children aged >12 years are at much greater risk. Membranous histologic changes increase thromboembolic risk at all ages; in particular, adults with membranous nephropathy have the highest reported risk (37.0%) and children with membranous histology have a rate (25%) that approaches the overall adult rate. There are striking, but variable, pathologic alterations of molecular hemostasis associated with nephrotic syndrome. No clear molecular therapeutic targets have been identified, but most studies show that the major pathologic changes involve antithrombin, fibrinogen, and factors V and VIII. There is inadequate evidence to support routine prophylactic therapy. Therapy includes anticoagulation in all cases, with thrombolysis reserved for those with the most severe thromboembolic disease. Future hemostatic research in nephrotic syndrome should focus on identifying cohorts at highest risk for thrombosis through the use of clinical markers and biomarkers as well as searching for molecular targets to correct the prothrombotic pathophysiology of this disease.
Topics: Adult; Animals; Anticoagulants; Blood Coagulation; Child; Child, Preschool; Fibrinolytic Agents; Humans; Infant; Nephrotic Syndrome; Risk Assessment; Risk Factors; Thromboembolism; Thrombolytic Therapy; Treatment Outcome
PubMed: 22344511
DOI: 10.2215/CJN.10131011 -
Trends in Cardiovascular Medicine Nov 2021Patients with atrial fibrillation experience higher mortality rates than those without this condition. Recent studies have explored whether mortality rates in atrial... (Review)
Review
Patients with atrial fibrillation experience higher mortality rates than those without this condition. Recent studies have explored whether mortality rates in atrial fibrillation patients and the overall impact of atrial fibrillation on mortality has changed. Overall, mortality in atrial fibrillation has decreased over the last few decades, with no strong differences between men and women. These improvements could be caused by advances in preventing thromboembolic complications of atrial fibrillation or better management of comorbidities in these patients. Understanding the mechanisms for these changes and developing novel approaches to improve survival in AF patients are areas deserving of future research.
Topics: Atrial Fibrillation; Comorbidity; Female; Humans; Male; Risk Factors; Thromboembolism
PubMed: 33127438
DOI: 10.1016/j.tcm.2020.10.010 -
Europace : European Pacing,... Aug 2020Cardioversion is widely used in patients with atrial fibrillation (AF) and atrial flutter when a rhythm control strategy is pursued. We sought to summarize the current...
Cardioversion is widely used in patients with atrial fibrillation (AF) and atrial flutter when a rhythm control strategy is pursued. We sought to summarize the current evidence on this important area of clinical management of patients with AF including electrical and pharmacological cardioversion, peri-procedural anticoagulation and thromboembolic complications, success rate, and risk factors for recurrence to give practical guidance.
Topics: Anticoagulants; Atrial Fibrillation; Atrial Flutter; Electric Countershock; Humans; Risk Factors; Thromboembolism
PubMed: 32337542
DOI: 10.1093/europace/euaa057 -
World Journal of Gastroenterology Oct 2014Patients with inflammatory bowel disease (IBD) have an increased risk of vascular complications. Thromboembolic complications, both venous and arterial, are serious... (Review)
Review
Patients with inflammatory bowel disease (IBD) have an increased risk of vascular complications. Thromboembolic complications, both venous and arterial, are serious extraintestinal manifestations complicating the course of IBD and can lead to significant morbidity and mortality. Patients with IBD are more prone to thromboembolic complications and IBD per se is a risk factor for thromboembolic disease. Data suggest that thrombosis is a specific feature of IBD that can be involved in both the occurrence of thromboembolic events and the pathogenesis of the disease. The exact etiology for this special association between IBD and thromboembolism is as yet unknown, but it is thought that multiple acquired and inherited factors are interacting and producing the increased tendency for thrombosis in the local intestinal microvasculature, as well as in the systemic circulation. Clinicians' awareness of the risks, and their ability to promptly diagnose and manage tromboembolic complications are of vital importance. In this review we discuss how thromboembolic disease is related to IBD, specifically focusing on: (1) the epidemiology and clinical features of thromboembolic complications in IBD; (2) the pathophysiology of thrombosis in IBD; and (3) strategies for the prevention and management of thromboembolic complications in IBD patients.
Topics: Blood Coagulation; Humans; Inflammation Mediators; Inflammatory Bowel Diseases; Prognosis; Risk Assessment; Risk Factors; Thromboembolism
PubMed: 25320522
DOI: 10.3748/wjg.v20.i38.13863 -
Blood Jan 2005Anticoagulants are pivotal agents for prevention and treatment of thromboembolic disorders. Limitations of existing anticoagulants, vitamin K antagonist and heparins,... (Review)
Review
Anticoagulants are pivotal agents for prevention and treatment of thromboembolic disorders. Limitations of existing anticoagulants, vitamin K antagonist and heparins, have led to the development of newer anticoagulant therapies. These anticoagulants have been designed to target specific coagulation enzymes or steps in the coagulation pathway. New anticoagulants that are under evaluation in clinical trials include: (1) inhibitors of the factor VIIa/tissue factor pathway; (2) factor Xa inhibitors, both indirect and direct; (3) activated protein C and soluble thrombomodulin; and (4) direct thrombin inhibitors. Although most of these are parenteral agents, several of the direct inhibitors of factor Xa and thrombin are orally active. Clinical development of these therapies often starts with studies in the prevention of venous thrombosis before evaluation for other indications, such as prevention of cardioembolism in patients with atrial fibrillation or prosthetic heart valves. At present, the greatest clinical need is for an oral anticoagulant to replace warfarin for long-term prevention and treatment of patients with venous and arterial thrombosis. Ximelagatran, an oral direct thrombin inhibitor, is the first of a series of promising new agents that might fulfill this need. Large phase 3 trials evaluating ximelagatran for the secondary prevention of venous thromboembolism and prevention of cardioembolic events in patients with atrial fibrillation have been completed.
Topics: Anticoagulants; Humans; Thromboembolism
PubMed: 15191946
DOI: 10.1182/blood-2003-12-4195 -
International Journal For Numerical... Oct 2022Thrombosis and thromboembolism are deadly risk factors in blood-contacting biomedical devices, and in-silico models of thrombosis are attractive tools to understand the...
Thrombosis and thromboembolism are deadly risk factors in blood-contacting biomedical devices, and in-silico models of thrombosis are attractive tools to understand the mechanics of these processes, though the simulation of thromboembolism remains underdeveloped. The purpose of this study is to modify an existing computational thrombosis model to allow for thromboembolism and to investigate the behavior of the modified model at a range of flow rates. The new and existing models are observed to lead to similar predictions of thrombosis in a canonical backward-facing step geometry across flow rates, and neither model predicts thrombosis in a turbulent flow. Simulations are performed by increasing flow rates in the case of a clot formed at lower flow to induce embolization. While embolization is observed, most of the clot breakdown is by shear rather than by breakup and subsequent transport of clotted material, and further work is required in the formulation and validation of embolization. This model provides a framework to further investigate thromboembolization.
Topics: Blood Flow Velocity; Computer Simulation; Humans; Models, Cardiovascular; Thromboembolism; Thrombosis
PubMed: 36220632
DOI: 10.1002/cnm.3638 -
Ugeskrift For Laeger Apr 2021The number of thrombophilia investigations has been steadily increasing over the past decade. However, it is debatable to what extent treatment of thromboembolic events... (Review)
Review
The number of thrombophilia investigations has been steadily increasing over the past decade. However, it is debatable to what extent treatment of thromboembolic events is further qualified by thrombophilia investigations. Based of the most recent literature as well as international and national expert opinions, this review provides a status on the frequency and severity of inherited and acquired thrombophilia, discusses indication for thrombophilia assessment, states the analyses to be included in the test panel, and the clinical implications that presence of thrombophilia may have.
Topics: Humans; Risk Factors; Thromboembolism; Thrombophilia
PubMed: 33913419
DOI: No ID Found