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

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

RMD Open ◽

10.1136/rmdopen-2021-001678 ◽

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.

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

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2019-15-4-593-603 ◽

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.

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

Lupus ◽

10.1177/0961203319889156 ◽

2019 ◽

Vol 29 (1) ◽

pp. 37-44 ◽

Cited By ~ 9

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.

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Direct Oral Anticoagulants in the Treatment of Left Ventricular Thrombus: A Retrospective, Multicenter Study and Meta-Analysis of Existing Data

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420967644 ◽

2020 ◽

pp. 107424842096764 ◽

Cited By ~ 2

Author(s):

John M. Cochran ◽

Xiaoming Jia ◽

Jessica Kaczmarek ◽

Kristen A. Staggers ◽

Mahmoud Al Rifai ◽

...

Keyword(s):

Controlled Trial ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Left Ventricular ◽

Left Ventricular Thrombus ◽

Coronary Syndrome ◽

Ventricular Thrombus ◽

Existing Data

Aim: To compare the safety and efficacy of direct oral anticoagulants (DOAC) relative to vitamin K antagonists (VKA) for the treatment of left ventricular thrombus (LVT). Methods: This retrospective study enrolled patients diagnosed with LVT from 2014-2017. Patient characteristics and outcomes within 12 months of LVT diagnosis were recorded and analyzed. A meta-analysis was also performed by pooling our results with existing data in literature. Results: 14 DOAC and 59 VKA patients were included. Baseline demographic and clinical characteristics were similar except for age. Although more strokes within 12 months occurred in VKA (15%) than in DOAC (0%) patients, this was not statistically significant (p = 0.189). There were no significant differences in outcomes between patients on DOAC and VKA for acute coronary syndrome (ACS) (7%, vs 3.4%, p = .477), LVT resolution (86% vs 76%, p = .499) or bleeding (14% vs 14%, p = 1) within 12 months. The meta-analysis included 6 studies (n = 408 for DOACs; n = 1207 for VKA). There were no significant differences between DOACs versus VKAs with respect to odds for unresolved thrombus (OR 0.61, 95% CI 0.26,1.41), embolic events (OR 1.24, 95% CI 0.90,1.69), embolic events and death (OR 1.10, 95% CI 0.84,1.45) or bleeding events (OR 1.13, 95% CI 0.74,1.72). Conclusions: Our study and meta-analysis suggest similar efficacy and safety of DOACs in the treatment of LVT compared to VKA. These findings underscore the need for a randomized controlled trial.

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Clinical features, management and outcomes of gastrointestinal bleeding in patients treated with oral anticoagulants

European Heart Journal ◽

10.1093/eurheartj/ehab724.0562 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

D Marti Sanchez ◽

B Biscotti Rodil ◽

F Delgado Calva ◽

J Duarte Torres ◽

A Marschall ◽

...

Keyword(s):

Clinical Course ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Red Blood Cell Transfusion ◽

Risk Scores ◽

High Dose ◽

Close Monitoring ◽

Gi Bleeding

Abstract Background Gastrointestinal (GI) bleeding with the different antithrombotics may present peculiarities in terms of location, precipitating factors, clinical management and prognosis. Purpose Our objective was to compare the profile and clinical course of GI bleeding with direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA). Methods We carried out a retrospective study of all consecutive patients treated in a tertiary hospital during 2018 and 2019, and who met the following selection criteria: 1) diagnosis of confirmed or probable GI bleeding; 2) red blood cell transfusion; 3) treatment with an oral anticoagulant; 4) absence of concomitant antiplatelet therapy. We collected information on comorbidities, bleeding risk scores, baseline treatments, and clinical course of bleeding. We compared adjusted all-cause mortality at 12-months between DOACs and VKAs groups. Results We identified 115 patients with GI bleeding, mean age 83±9 years, 63% women, 50.4% on DOACs and 49.6% on VKAs. NOACs group showed more recent anticoagulation history, and more complex clinical profile, with older age (85 vs. 82 years, p=0.026), number of comorbidities (2.7 vs. 2.1, p=0.049), CHA2DS2VASc score (5.2 vs. 4.2, p=0.001) and ORBIT score (3.9 vs. 3.3, p=0.047). There were no differences in the location of bleeding (60.5% lower GI tract), number of units transfused (mean 2.6), or hemoglobin nadir (mean 7.6 g/dL). Notably, 42% of the patients on DOACs were receiving the high dose at the time of bleeding, 63% of them had some risk criterion for overdose (age>80 years, weight <60 kg, moderate P-glycoprotein inhibitors), and 37% had >1 of these criteria. 12-month cumulative mortality was high, but significantly lower in the DOACs group (15.5% vs. 35.7%, adjusted HR 0.31, p=0.002). Conclusions Patients who experience GI bleeding with anticoagulants represent a therapeutic challenge, with both high age and prevalence of comorbidities. One-year mortality is remarkably high, particularly in the VKA group. Our findings emphasize the need for close monitoring and optimization of preventive strategies in this complex clinical scenario. FUNDunding Acknowledgement Type of funding sources: None.

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Safety of direct oral anticoagulants in older adults with atrial fibrillation: a systematic review and meta-analysis of (subgroup analyses from) randomized controlled trials

10.21203/rs.3.rs-445458/v1 ◽

2021 ◽

Author(s):

Katharina Doni ◽

Stefanie Bühn ◽

Alina Weise ◽

Nina-Kristin Mann ◽

Simone Hess ◽

...

Keyword(s):

Atrial Fibrillation ◽

Older Adults ◽

Low Dose ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

High Dose ◽

Meta Analyses

Abstract PurposeOur objective was to assess the safety of long-term intake of DOACs in older adults with atrial fibrillation (AF). MethodsWe included RCTs in elderly (≥65 years) patients with AF. A systematic search in MEDLINE and EMBASE was performed on 9/11/2020. For determination of risk of bias, the RoB-2 tool was applied. We pooled outcomes using random-effects meta-analyses. The quality of evidence was assessed using GRADE.ResultsTen RCTs with a total of 61,948 patients were identified. Seven RCTs included patients with AF-only and three with AF who received PCI and additional antiplatelet-therapy. Two RCTs compared apixaban with either warfarin or aspirin, three edoxaban with either placebo, aspirin, or Vitamin K antagonists (VKAs), two dabigatran with warfarin and three rivaroxaban with warfarin. DOACs probably reduce mortality in elderly patients with AF-only (HR 0.89 95%CI 0.78 to 1.02). We did not find any RCT that reported mortality in elderly AF-PCI patients. Low-dose DOACs likely reduce bleeding compared to VKAs (HR ranged from 0.47 to 1.01). High-dose edoxaban reduces major or clinically relevant bleeding (MCRB) compared to VKAs (HR 0.82 95%CI 0.73 to 0.93) but high-dose dabigatran or rivaroxaban increase MCRB (HR 1.15 95%CI 1.02 to 1.30).Conclusion We found that low-dose DOACs probably decrease mortality in AF-only patients. Moreover, apixaban and edoxaban are associated with fewer MCRB compared to VKAs. For dabigatran and rivaroxaban, the risk of MCRB varies depending on dose.

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Treatment of Vascular Thrombosis in Antiphospholipid Syndrome: An Update

Hämostaseologie ◽

10.1055/s-0040-1701473 ◽

2020 ◽

Vol 40 (01) ◽

pp. 031-037

Author(s):

Lida Kalmanti ◽

Edelgard Lindhoff-Last

Keyword(s):

Risk Factors ◽

Antiphospholipid Syndrome ◽

Pregnancy Complications ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Vascular Events ◽

Asymptomatic Patients

AbstractThe antiphospholipid syndrome (APS) is an acquired autoimmune disorder associated with arterial, venous, or microvascular thrombosis and/or pregnancy complications mainly in young age. The diagnosis is made by the persistent detection of anticardiolipin antibodies, β2-glycoprotein I antibodies (β2GPIA), and/or lupus anticoagulants (LAs) for at least 12 weeks. Patients should present with at least one clinical and one laboratory criterion. Patients presenting with all three types of antibodies and vascular events are high-risk patients and should receive vitamin K antagonists (VKAs) as long as the antibodies persist. In patients with prior arterial thrombosis, VKA with or without low-dose aspirin is the current treatment of choice. The international normalized ratio (INR) should be between 2 and 3 although in some cases keeping the target INR above 3 may be necessary. Patients with venous thrombosis and negative LA may alternatively be treated with direct oral anticoagulants although more data are needed. Minimizing vascular risk factors is always necessary in APS patients. Aspirin can be given as primary prevention in asymptomatic patients with positive antiphospholipid antibodies without thrombosis or pregnancy complications especially when additional vascular risk factors are present. Catastrophic APS occurs in less than 1% of APS patients and presents as a thrombotic storm. Early use of a combined triple therapy such as anticoagulation, plasma exchange, and steroids with either or not addition of immunoglobulins is important to reduce mortality.

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Direct oral anticoagulants: A new chapter in anticoagulation therapy

Arhiv za farmaciju ◽

10.5937/arhfarm2005249s ◽

2020 ◽

Vol 70 (5) ◽

pp. 249-268

Author(s):

Radica Stepanović-Petrović ◽

Katarina Nastić

Keyword(s):

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Cardiac Biomarkers ◽

Bleeding Complications ◽

Comparable Efficacy ◽

Thrombin Inhibitor ◽

Severe Bleeding ◽

Coronary Syndrome

Thromboembolic events are the leading cause of morbidity and mortality worldwide. From the second half of the 20th century, vitamin K antagonists (VKAs), warfarin and acenocoumarol, were the only anticoagulants taken orally. The major reform in anticoagulation therapy was made by the advent of direct oral anticoagulants (DOACs), about 10 years ago. Direct thrombin inhibitor (dabigatran) and direct inhibitors of factor Xa (rivaroxaban, apixaban, edoxaban, and betrixaban) have demonstrated favorable risk/benefit ratio. Compared to warfarin, DOACs are associated with a predictable pharmacokinetic profile, lower severe bleeding complications, particularly intracranial hemorrhages, and minimal drug interactions. Moreover, DOACs achieve a rapid onset of action and have shown comparable efficacy with warfarin and low molecular weight heparin (LMWH) in clinical trials. As a result, DOACs are now replacing VKAs and LMWH for many indications including stroke and systemic embolism prevention in nonvalvular atrial fibrillation, prevention, and treatment of venous thromboembolism and thromboprophylaxis following total knee/hip replacement surgery. In addition, rivaroxaban (in combination with aspirin alone or aspirin and clopidogrel) is used in the prevention of atherothrombotic events following acute coronary syndrome with elevated cardiac biomarkers. In case of severe bleeding complications under DOACs treatment, antidotes are available; idarucizumab for dabigatran reversal and andexanet alfa for rivaroxaban and apixaban.

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Direct Oral Anticoagulants for Thromboprophylaxis in Patients with Antiphospholipid Syndrome

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0036-1597902 ◽

2017 ◽

Vol 44 (05) ◽

pp. 427-438 ◽

Cited By ~ 8

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.

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Antiphospholipid syndrome and challenges with direct oral anticoagulants

British Journal of Hospital Medicine ◽

10.12968/hmed.2020.0080 ◽

2020 ◽

Vol 81 (5) ◽

pp. 1-11

Author(s):

Stephen Booth ◽

Kieran Burton ◽

Beverley Hunt ◽

Michael Desborough

Keyword(s):

Venous Thromboembolism ◽

Antiphospholipid Syndrome ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Prevention Of Thrombosis ◽

Cardiolipin Antibodies ◽

Randomised Control Trials

Direct oral anticoagulants have become the mainstay of the management of venous thromboembolism and atrial fibrillation, and long-term anticoagulation is indicated for those at high risk of further thrombotic events. This includes patients diagnosed with antiphospholipid syndrome, for whom the ‘triple positive’ laboratory combination of lupus anticoagulant, β2-glycoprotein-1 and anti-cardiolipin antibodies signify those at greatest risk. Data from meta-analysis and randomised control trials have raised the concern that direct oral anticoagulants may be less effective than vitamin K antagonists for the prevention of thrombosis in patients with thrombotic antiphospholipid syndrome, particularly those with the triple positive profile. This article reviews the diagnosis of thrombotic antiphospholipid syndrome, strategies for testing without interruption of anticoagulation, evidence concerning the safety of direct oral anticoagulants in this setting, and the implications for current investigation and management of unprovoked venous thromboembolism.

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