scholarly journals Direct Oral Anticoagulants for Thromboprophylaxis in Patients with Antiphospholipid Syndrome

2017 ◽  
Vol 44 (05) ◽  
pp. 427-438 ◽  
Author(s):  
Maria Efthymiou ◽  
Carolyn Gates ◽  
David Isenberg ◽  
Hannah Cohen
Keyword(s):  
Antiphospholipid Syndrome ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
International Normalized Ratio ◽  
Wide Range ◽  
Variable Sensitivity ◽  
Definition Of ◽  
Therapeutic Alternatives

AbstractThe current mainstay of the treatment and secondary thromboprophylaxis of thrombotic antiphospholipid syndrome (APS) is anticoagulation with warfarin or other vitamin K antagonists (VKAs). In addition to their well-known limitations, VKAs are often problematic in APS patients because of the variable sensitivity of thromboplastins to lupus anticoagulant. As a result, the international normalized ratio may not accurately reflect the intensity of anticoagulation. Direct oral anticoagulants (DOACs) are established as therapeutic alternatives to VKAs for a wide range of indications, including the treatment and secondary prevention of venous thromboembolism. Definition of the role of DOACs in the treatment of thrombotic APS is emerging with the results of recent and ongoing clinical studies. This review focuses on the current situation with regard to DOACs for secondary thromboprophylaxis in APS and issues pertinent to DOAC use in APS patients, as well as potential future directions.

scholarly journals Direct oral anticoagulants versus vitamin K antagonists in patients with antiphospholipid syndrome: systematic review and meta-analysis

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001678
Author(s):  
Nazariy Koval ◽  
Mariana Alves ◽  
Rui Plácido ◽  
Ana G Almeida ◽  
João Eurico Fonseca ◽  
...  
Keyword(s):  
Systematic Review ◽  
Antiphospholipid Syndrome ◽  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Thromboembolic Events ◽  
Bleeding Events ◽  
Prevention Of Thromboembolic Events

BackgroundDespite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral anticoagulants/direct oral anticoagulants (DOACs) have been used off-label.ObjectiveWe aimed to perform a systematic review comparing DOACs to VKA regarding prevention of thromboembolic events, occurrence of bleeding events and mortality in patients with APS.MethodsAn electronic database search was performed through MEDLINE, CENTRAL and Web of Science. After data extraction, we pooled the results using risk ratio (RR) and 95% CI. Heterogeneity was assessed using the I². The outcomes considered were all thromboembolic events as primary, and major bleeding, all bleeding events and mortality as secondary. Evidence confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology.ResultsWe included 7 studies and a total of 835 patients for analyses. Thromboembolic events were significantly increased in DOACs arm, compared with VKA—RR 1.69, 95% CI 1.09 to 2.62, I²—24%, n=719, 6 studies. In studies using exclusively rivaroxaban, which was the most representative drug in all included studies, the thromboembolic risk was increased threefold (RR 3.36, 95% CI 1.53 to 7.37). The risks of major bleeding, all bleeding events and mortality were not significantly different from control arm. The grade of certainty of our results is very low.ConclusionsCurrent evidence suggests DOACs use, particularly rivaroxaban, among patients with APS, is less effective than VKA since it is associated with 69% increased risk of thromboembolic events.Trial registration numberCRD42020216178.

scholarly journals Optimization of Pharmacotherapy with Direct Oral Anticoagulants: the Need to Choose the Right Dosage Regimen

2019 ◽  
Vol 15 (4) ◽  
pp. 593-603
Author(s):  
A. I. Kochetkov ◽  
O. D. Ostroumova
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Coronary Intervention ◽  
International Normalized Ratio ◽  
Efficacy And Safety ◽  
High Efficacy ◽  
Drug Label ◽  
Coronary Syndrome ◽  
Number Of Patients

In recent years, there has been a persistent trend towards the more frequent prescription of direct oral anticoagulants (DOACs) compared with vitamin K antagonists due to the extensive body of evidence showing their high safety and efficacy, which in some cases exceed those of warfarin, and also by reason of there is no necessity for regular monitoring of international normalized ratio. However, the question of the reasonable and rational prescription of DOACs becomes relevant, including issues of their dosing, especially as a result of increasing in the number of patients with a complex cardiovascular risk profile and multimorbidity. In these terms, apixaban stands high among the DOAC class, and its high efficacy and safety both in full dose and reasonably reduced dosage has been proved, including older patients, patients with chronic kidney disease, coronary artery disease, with history of acute coronary syndrome and individuals undergoing percutaneous coronary intervention. This DOAC has strict indications to reduce the dose, they are specified in the drug label, and in such cases a reduced dose should be prescribed, in these clinical conditions the effectiveness and safety of apixaban is also proven. The favorable apixaban pharmacokinetic properties, consisting in low renal clearance, lack of clinically relevant interaction with food and the linear smooth effect on the blood coagulation components without episodes of hypo- and hypercoagulation, are the most important components of high efficacy and safety of this DOAC. The optimal efficacy and safety coupling of apixaban is reflected in the exclusively high patients’ adherence to the treatment confirmed by evidence-based medicine data, and therefore there is no necessity for additional procedures to maintain adherence. All the aforementioned facts allow us to recommend apixaban for widespread use in patients requiring anticoagulant therapy for optimal prevention of systemic thromboembolism and minimizing the associated risk of bleeding.

scholarly journals “A Tale of Two Cities”: Anticoagulation Management in Patients with Atrial Fibrillation and Prosthetic Valves in the Era of Direct Oral Anticoagulants

Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 437
Author(s):  
Giuseppe Palmiero ◽  
Enrico Melillo ◽  
Antonino Salvatore Rubino
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Valvular Heart Disease ◽  
Therapeutic Option ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Management ◽  
Prosthetic Valves

Valvular heart disease and atrial fibrillation often coexist. Oral vitamin K antagonists have represented the main anticoagulation management for antithrombotic prevention in this setting for decades. Novel direct oral anticoagulants (DOACs) are a new class of drugs and currently, due to their well-established efficacy and security, they represent the main therapeutic option in non-valvular atrial fibrillation. Some new evidences are exploring the role of DOACs in patients with valvular atrial fibrillation (mechanical and biological prosthetic valves). In this review we explore the data available in the medical literature to establish the actual role of DOACs in patients with valvular heart disease and atrial fibrillation.

scholarly journals Direct oral anticoagulants in patients with antiphospholipid syndrome: a cohort study

Lupus ◽  
2019 ◽  
Vol 29 (1) ◽  
pp. 37-44 ◽  
Author(s):  
K Malec ◽  
E Broniatowska ◽  
A Undas
Keyword(s):  
Cohort Study ◽  
Antiphospholipid Syndrome ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real Life ◽  
Double Positive ◽  
Increased Risk ◽  
Long Term Follow Up

Objectives Despite controversies, direct oral anticoagulants (DOACs) are increasingly used in antiphospholipid syndrome (APS). We investigated the safety and efficacy of DOACs versus vitamin K antagonists (VKAs) in real-life consecutive APS patients. Patients and methods In a cohort study of 176 APS patients, which included 82 subjects who preferred DOACs or had unstable anticoagulation with VKAs, we recorded venous thromboembolism (VTE), cerebrovascular ischemic events or myocardial infarction, along with major bleeding or clinically relevant non-major bleeding (CRNMB). Results APS patients were followed for a median time of 51 (interquartile range 43–63) months. Patients on DOACs and those on VKAs were similar with regard to baseline characteristics. APS patients treated with DOACs had increased risk of recurrent thromboembolic events and recurrent VTE alone compared with those on VKAs (hazard ratio (HR) = 3.98, 95% confidence interval (CI): 1.54–10.28, p = 0.004 and HR = 3.69, 95% CI: 1.27–10.68, p = 0.016, respectively) with no differences between rivaroxaban and apixaban or single- or double-positive and triple-positive APS. Thromboembolism on DOACs was associated with older age (median 52 versus 42 years, p = 0.008) and higher global APS score (median 13 versus 8.5, p = 0.013). Patients on DOACs had increased risk of major bleeding or CRNMB (HR = 3.63, 95% CI: 1.53–8.63, p = 0.003), but rates of gastrointestinal bleeds (HR = 3.36, 95% CI: 0.70–16.16, p = 0.13) and major bleeds or CRNMB other than heavy menstrual bleeding (HR = 2.45, 95% CI: 0.62–9.69, p = 0.2) were similar in both treatment groups. Conclusion During long-term follow-up of real-life APS patients, DOACs are less effective and less safe as VKAs in the prevention of thromboembolism.

scholarly journals Direct Oral Anticoagulants after Ischemic Stroke: Which Patient? Which Drug? And How Early?

2021 ◽  
Vol 41 (01) ◽  
pp. 031-034
Author(s):  
Gian Marco De Marchis
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Ischemic Stroke ◽  
Vitamin K ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Reversal Agents

AbstractDirect oral anticoagulants (DOACs) are recommended over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and ischemic stroke. The main advantage of DOAC over VKA is the lower rate of bleeding and mortality. This review covers challenges clinicians can encounter when treating patients with AF and ischemic stroke, including timing of DOAC start and ongoing randomized clinical trials, appropriate dosing, and available comparative evidence across DOACs. For patients without AF but with an ischemic stroke, the review outlines the role of DOACs. Finally, the risk of thrombotic events associated with specific DOAC reversal agents and DOAC pausing is reviewed.

New Avenues for Optimal Treatment of Atrial Fibrillation and Stroke Prevention

Stroke ◽  
2021 ◽  
Author(s):  
Gian Marco De Marchis ◽  
Luciano A. Sposato ◽  
Michael Kühne ◽  
Tolga D. Dittrich ◽  
Leo H. Bonati ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Interdisciplinary Approach ◽  
Left Atrial Appendage Occlusion ◽  
High Risk Populations

One in 3 individuals free of atrial fibrillation (AF) at index age 55 years is estimated to develop AF later in life. AF increases not only the risk of ischemic stroke but also of dementia, even in stroke-free patients. In this review, we address recent advances in the heart-brain interaction with focus on AF. Issues discussed are (1) the timing of direct oral anticoagulants start following an ischemic stroke; (2) the comparison of direct oral anticoagulants versus vitamin K antagonists in early secondary stroke prevention; (3) harms of bridging with heparin before direct oral anticoagulants; (4) importance of appropriate direct oral anticoagulants dosing; (5) screening for AF in high-risk populations, including the role of wearables; (6) left atrial appendage occlusion as an alternative to oral anticoagulation; (7) the role of early rhythm-control therapy; (8) effect of lifestyle interventions on AF; (9) AF as a risk factor for dementia. An interdisciplinary approach seems appropriate to address the complex challenges posed by AF.

scholarly journals Updates on Anticoagulation and Laboratory Tools for Therapy Monitoring of Heparin, Vitamin K Antagonists and Direct Oral Anticoagulants

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 264
Author(s):  
Osamu Kumano ◽  
Kohei Akatsuchi ◽  
Jean Amiral
Keyword(s):  
Dose Adjustment ◽  
Therapy Monitoring ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Monitoring Methods ◽  
Anticoagulant Drugs

Anticoagulant drugs have been used to prevent and treat thrombosis. However, they are associated with risk of hemorrhage. Therefore, prior to their clinical use, it is important to assess the risk of bleeding and thrombosis. In case of older anticoagulant drugs like heparin and warfarin, dose adjustment is required owing to narrow therapeutic ranges. The established monitoring methods for heparin and warfarin are activated partial thromboplastin time (APTT)/anti-Xa assay and prothrombin time – international normalized ratio (PT-INR), respectively. Since 2008, new generation anticoagulant drugs, called direct oral anticoagulants (DOACs), have been widely prescribed to prevent and treat several thromboembolic diseases. Although the use of DOACs without routine monitoring and frequent dose adjustment has been shown to be safe and effective, there may be clinical circumstances in specific patients when measurement of the anticoagulant effects of DOACs is required. Recently, anticoagulation therapy has received attention when treating patients with coronavirus disease 2019 (COVID-19). In this review, we discuss the mechanisms of anticoagulant drugs—heparin, warfarin, and DOACs and describe the methods used for the measurement of their effects. In addition, we discuss the latest findings on thrombosis mechanism in patients with COVID-19 with respect to biological chemistry.

scholarly journals Cerebral Ischemia in Patients on Direct Oral Anticoagulants

Stroke ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 873-879 ◽  
Author(s):  
Kosmas Macha ◽  
Armin Marsch ◽  
Gabriela Siedler ◽  
Lorenz Breuer ◽  
Erwin F. Strasser ◽  
...  
Keyword(s):  
Vitamin K ◽  
Plasma Levels ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
International Normalized Ratio ◽  
Large Vessel ◽  
Stroke Severity ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion

Background and Purpose— In patients with ischemic stroke on therapy with vitamin K antagonists, stroke severity and clinical course are affected by the quality of anticoagulation at the time of stroke onset, but clinical data for patients using direct oral anticoagulants (DOACs) are limited. Methods— Data from our registry including all patients admitted with acute cerebral ischemia while taking oral anticoagulants for atrial fibrillation between November 2014 and October 2017 were investigated. The activity of vitamin K antagonists was assessed using the international normalized ratio on admission and categorized according to a threshold of 1.7. DOAC plasma levels were measured using the calibrated Xa-activity (apixaban, rivaroxaban, and edoxaban) or the Hemoclot-assay (dabigatran) and categorized into low (<50 ng/mL), intermediate (50–100 ng/mL), or high (>100 ng/mL). Primary objective was the association between anticoagulant activity and clinical and imaging characteristics. Results— Four hundred sixty patients were included (49% on vitamin K antagonists and 51% on DOAC). Patients on vitamin K antagonists with low international normalized ratio values had higher scores on the National Institutes of Health Stroke Scale and a higher risk of large vessel occlusion on admission. For patients on DOAC, plasma levels were available in 75.6% and found to be low in 49 (27.7%), intermediate in 41 (23.2%), and high in 87 patients (49.2%). Low plasma levels were associated with higher National Institutes of Health Stroke Scale scores on admission (low: 8 [interquartile range, 3–15] versus intermediate: 4 [1–11] versus high: 3 [0–8]; P <0.001) and higher risk of persisting neurological deficits or cerebral infarction on imaging (85.7% versus 75.6% versus 54.0%; P <0.001). Low DOAC plasma levels were an independent predictor of large vessel occlusion (odds ratio, 3.84 [95% CI, 1.80–8.20]; P =0.001). Conclusions— The activity of anticoagulation measured by specific DOAC plasma levels on admission is associated with stroke severity and presence of large vessel occlusion.

scholarly journals P168 Non-bacterial endocarditis in patients with antiphospholipid syndrome treated with direct oral anticoagulants

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
I Munoz Pousa ◽  
F E Calvo Iglesias ◽  
M Cespon Fernandez ◽  
E Lopez Rodriguez ◽  
G Pradas Montilla ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
High Dose ◽  
Primary Antiphospholipid Syndrome ◽  
Poor Control ◽  
Mechanical Prosthesis ◽  
Coronary Syndrome ◽  
Dose Warfarin

Abstract Introduction Primary antiphospholipid syndrome (APS) is a hypercoagulability state of autoimmune origin. Vitamin K- antagonists remain the mainstay therapy though the difficulties in maintaining target therapeutic range contributed to prescriptions of direct oral anticoagulants (ACOD). A recent randomized trial reported an excess in thromboembolic events in patients under rivaroxaban therapy compared with warfarin. Purpose Description of two cases of Libman-Sacks endocarditis in APS patients on therapy with rivaroxaban due to poor control with coumadin. Methods and results. Case 1 is a 47-year-old woman and case 2 a 69-yo man with APS with high antibody titers of 3 classes and previous thrombotic events (pulmonary embolism in case 1 and acute coronary syndrome in case 2). In both cases, coumadin was switched to rivaroxaban because of poor control. During follow-up the diagnosis of blood culture-negative endocarditis was stablished in both cases. Echo examinations in case 1 revealed a 12 mm mobile vegetation in the ventricular face of the non-coronary aortic cusp, which resolved after 2 months high-dose warfarin therapy. Case 2 was admitted to hospital because of heart failure. TTE and TOE revealed a 26 mm mass attached to the atrial face of posterior mitral leaflet and moderate mitral regurgitation. He underwent mitral valve replacement with a mechanical prosthesis and the final pathologic diagnosis was Libman-Sacks endocarditis. Conclusions Libman-Sacks endocarditis as a thrombotic feature of high-risk APS patients can occur under rivaroxaban therapy. In one of our 2 cases, high-dose coumadin therapy resolved this complication Abstract P168 Figure. Cases

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