Protocol Modification of Apixaban for the Secondary Prevention of Thrombosis Among Patients With Antiphospholipid Syndrome Study.
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ABSTRACT:
SUBMITTER: Woller SC
PROVIDER: S-EPMC6714642 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
Publications
Protocol Modification of Apixaban for the Secondary Prevention of Thrombosis Among Patients With Antiphospholipid Syndrome Study.
Woller Scott C SC Stevens Scott M SM Kaplan David A DA T Rondina Matthew M
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 20170912 1
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Project description:Antiphospholipid syndrome (APS) is an acquired autoimmune condition characterized by thrombotic events, pregnancy morbidity, and laboratory evidence of antiphospholipid antibodies (aPL). Management of these patients includes the prevention of a first thrombotic episode in at-risk patients (primary prevention) and preventing recurrent thrombotic complications in patients with a history of thrombosis (secondary prevention). Assessment of thrombotic risk in these patients, balanced against estimated bleeding risks associated with antithrombotic therapy could assist clinicians in determining whether antithrombotic therapy is warranted. Thrombotic risk can be assessed by evaluating a patient's aPL profile and additional thrombotic risk factors. Although antithrombotic options for secondary prevention of venous thromboembolism (VTE) have been evaluated in clinical trials, studies in primary prevention of asymptomatic aPL-positive patients are needed. Primary prevention with aspirin may be considered in asymptomatic patients who have a high-risk aPL profile, particularly if additional risk factors are present. Secondary prevention with long-term anticoagulation is recommended based on estimated risks of VTE recurrence, although routine evaluation of thrombotic risk can assist in determining whether ongoing anticoagulation is warranted. Studies that stratify thrombotic risk in aPL-positive patients, and patients with APS evaluating antithrombotic and non-antithrombotic therapies will be useful in optimizing the management of these patients.
| S-EPMC6142449 | biostudies-literature
Project description:Thrombotic antiphospholipid syndrome (TAPS) is characterized by venous, arterial, or microvascular thrombosis. Patients with TAPS merit indefinite anticoagulation, and warfarin has historically been the standard treatment. Apixaban is an oral factor Xa inhibitor anticoagulant that requires no dose adjustment or monitoring. The efficacy and safety of apixaban compared with warfarin for TAPS patients remain unknown. This multicenter prospective randomized open-label blinded endpoint study assigned anticoagulated TAPS patients to apixaban or warfarin (target international normalized ratio 2-3) for 12 months. The primary efficacy outcome was clinically overt thrombosis and vascular death. Apixaban was first given at 2.5 mg twice daily. Two protocol changes were instituted based on recommendations from the data safety monitoring board. After the twenty-fifth patient was randomized, the apixaban dose was increased to 5 mg twice daily, and after the thirtieth patient was randomized, subjects with prior arterial thrombosis were excluded. Primary outcomes were adjudicated by independent experts blinded to treatment allocation. Patients randomized between 23 February 2015 and 7 March 2019 to apixaban (n = 23) or warfarin (n = 25) were similar. Among the components of the primary efficacy outcome, only stroke occurred in 6 of 23 patients randomized to apixaban compared with 0 of 25 patients randomized to warfarin. The study ended prematurely after the forty-eighth patient was enrolled. Conclusions from our study are limited due to protocol modifications and low patient accrual. Despite these limitations, our results suggest that apixaban may not be routinely substituted for warfarin to prevent recurrent thrombosis (especially strokes) among patients with TAPS. This trial was registered at www.clinicaltrials.gov as #NCT02295475.
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Project description:Background Antiphospholipid syndrome (APS) is an acquired thrombophilia that can be associated with decreased platelet counts. Case A 67-year-old woman presented with thrombocytopenia and a symptomatic right atrial mass suspicious of cardiac myxoma. Prolongation of the activated partial thromboplastin time (aPTT) was caused by a strong lupus anticoagulant, and bone marrow cytology was consistent with accelerated platelet clearance. The patient underwent uneventful resection of the atrial tumor, which turned out to be a calcified fibrin-rich thrombus. Definitive APS was diagnosed and long-term anticoagulation recommended. Conclusion When evaluating patients with right atrial masses, findings of thrombocytopenia and/or aPTT prolongation should raise the suspicion of APS-associated thrombosis.
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Project description:Clinical guidelines recommend warfarin for patients with antiphospholipid syndrome (APS) and ischemic stroke; however, robust evidence is lacking. We investigated the clinical benefits of different categories of antithrombotic medications in ischemic stroke patients positive for antiphospholipid antibodies (aPLs) in real-world practice. We reviewed data from patients with ischemic stroke or transient ischemic attack who tested positive for aPLs. Based on their secondary preventive antithrombotic medications, patients were classified into antiplatelet and anticoagulant categories, and further into warfarin, single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), and direct oral anticoagulant groups. The outcome of interest was a composite of recurrent thrombosis and major bleeding events. Time-varying Cox proportional hazards model was used. Among 167 eligible patients, 28 experienced composite outcome events over 601.1 person-years. SAPT and DAPT demonstrated clinical benefits over warfarin (SAPT vs. warfarin, adjusted hazard ratio [95% confidence intervals], 0.24 [0.07-0.83]; DAPT vs. warfarin, 0.25 [0.08-0.81]). Notably, DAPT was advantageous regarding major bleeding (DAPT vs. warfarin, 0.10 [0.02-0.47]), while the risk of recurrent thrombotic events was comparable between the antiplatelet and warfarin groups. Antiplatelet therapy may be a safe and effective alternative to warfarin for secondary prevention of aPL- and APS-related stroke. Further prospective validation is required.
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Project description:Q fever is a neglected and potentially fatal disease. During acute Q fever, antiphospholipid antibodies are very prevalent and have been associated with fever, thrombocytopenia, acquired heart valve disease, and progression to chronic endocarditis. However, thrombosis, the main clinical criterion of the 2006 updated classification of the antiphospholipid syndrome, has not been assessed in this context. To test whether thrombosis is associated with antiphospholipid antibodies and whether the criteria for antiphospholipid syndrome can be met in patients with acute Q fever, we conducted a cross-sectional study at the French National Referral Center for Q fever.Patients included were diagnosed with acute Q fever in our Center between January 2007 and December 2015. Each patient's history and clinical characteristics were recorded with a standardized questionnaire. Predictive factors associated with thrombosis were assessed using a rare events logistic regression model. IgG anticardiolipin antibodies (IgG aCL) assessed by an enzyme-linked immunosorbent assay were tested on the Q fever diagnostic serum. A dose-dependent relationship between IgG aCL levels and thrombosis was tested using a receiver operating characteristic (ROC) analysis.Of the 664 patients identified for inclusion in the study, 313 (47.1%) had positive IgG aCL and 13 (1.9%) were diagnosed with thrombosis. Three patients fulfilled the antiphospholipid syndrome criteria. After multiple adjustments, only positive IgG aCL (relative risk, 14.46 [1.85-113.14], P = .011) were independently associated with thrombosis. ROC analysis identified a dose-dependent relationship between IgG aCL levels and occurrence of thrombosis (area under curve, 0.83, 95%CI [0.73-0.93], P < .001).During acute Q fever, antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and acquired valvular heart disease. Antiphospholipid antibodies should be systematically assessed in acute Q fever patients. Hydroxychloroquine, which has been previously shown to antagonize IgG aCL pathogenic properties, should be tested in acute Q fever patients with anticardiolipin antibodies to prevent antiphospholipid-associated complications.Key Point: In addition to fever, thrombocytopenia and acquired valvular heart disease, antiphospholipid antibodies are associated with thrombosis during acute Q fever.
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Project description:No data is available about pharmacological secondary prevention of superficial vein thrombosis (SVT) despite 10-15% of patients develop venous thromboembolic complications at 3-6 months after an adequate treatment of the acute phase. To verify efficacy and safety of mesoglycan in secondary prevention of SVT recurrence and venous thromboembolic complications. Phase III multicenter, double-blind, randomized, superiority trial comparing mesoglycan 50 mg bid vs placebo in consecutive patients with a SVT extended at least 5 cm, after the initial 45-day treatment course with fondaparinux 2.5 mg once-daily. Primary efficacy outcome: SVT recurrence/extension, symptomatic venous thromboembolism (VTE), asymptomatic proximal deep-vein thrombosis, death. Primary safety outcome: major bleeding. We hypothesized a 12-month 15% incidence of the primary efficacy outcome in placebo group and a 50% risk reduction in mesoglycan group. A bilateral log-rank test with a sample of 650 patients (randomization 1:1) reach a 90% power, with an α-error of 0.025, of detecting a 7.0% difference (HR = 0.51) after 12 months of treatment, considering a 10% patients drop-out. At deadline (December 31, 2022) 570 patients have been randomized (10% drop rate). Mean age was 63.9 years, 58.8% were women. SVT involved great saphenous vein in 69.3%, small saphenous vein in 13.1%, and collaterals in 17.6% of patients. SVT was the first event in 61.7%, a recurrence in 38.3%, provoked in 50.2% and unprovoked in 49.8%. Patients not experiencing a primary outcome, or not retiring their consent will be followed up to December 31, 2024 when the final data analysis will be performedClinicalTrials.gov: NCT03428711.
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Project description:Potentiation of neutrophil extracellular trap (NET) release is one mechanism by which antiphospholipid antibodies (aPL Abs) effect thrombotic events in patients with antiphospholipid syndrome (APS). Surface adenosine receptors trigger cyclic AMP (cAMP) formation in neutrophils, and this mechanism has been proposed to regulate NETosis in some contexts. Here we report that selective agonism of the adenosine A2A receptor (CGS21680) suppresses aPL Ab-mediated NETosis in protein kinase A-dependent fashion. CGS21680 also reduces thrombosis in the inferior vena cavae of both control mice and mice administered aPL Abs. The antithrombotic medication dipyridamole is known to potentiate adenosine signaling by increasing extracellular concentrations of adenosine and interfering with the breakdown of cAMP. Like CGS21680, dipyridamole suppresses aPL Ab-mediated NETosis via the adenosine A2A receptor and mitigates venous thrombosis in mice. In summary, these data suggest an anti-inflammatory therapeutic paradigm in APS, which may extend to thrombotic disease in the general population.
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