edoxaban and Aortic-Valve-Stenosis

It is unknown whether edoxaban versus dual antiplatelet therapy (DAPT) has differential treatment effects on leaflet thrombosis, cerebral thromboembolism, and neurologic or neurocognitive dysfunction according to clinical and anatomic factors after transcatheter aortic valve implantation. To investigate the relative effects of edoxaban and DAPT on leaflet and cerebral thromboembolism in patients with major risk factors. The primary end point of this study was the incidence of leaflet thrombosis on computed tomography at 6 months. The secondary end points were new cerebral lesions on brain magnetic resonance imaging and neurologic and neurocognitive dysfunction between baseline and 6-month follow-up. Cox regression models assessed the consistency of the treatment effects in the prespecified subgroups. The favorable effect of edoxaban versus DAPT on the leaflet thrombosis was consistent across multiple clinical or anatomic subgroups, without significant interaction between the drug effect and each subgroup (p for interaction for age = 0.597, gender = 0.557, body mass index = 0.866, Society of Thoracic Surgeons score = 0.307, valve type = 0.702, edoxaban reduction criteria = 0.604, and valve morphology = 0.688). However, the incidence of new cerebral lesions on brain magnetic resonance imaging and worsening of neurologic and neurocognitive function were not significantly different between the groups among the various key subgroups. The relative effects of edoxaban and DAPT on the risk of leaflet thrombosis, cerebral thromboembolism, and neurologic dysfunction were consistent across a diverse spectrum of clinical or anatomical factors. Further studies are required to define tailored antithrombotic therapy for high-risk groups with specific clinical or anatomic characteristics.

Topics: Aortic Valve; Aortic Valve Stenosis; Female; Humans; Infant; Intracranial Thrombosis; Male; Platelet Aggregation Inhibitors; Thromboembolism; Thrombosis; Transcatheter Aortic Valve Replacement; Treatment Outcome

Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Atrial Fibrillation; Female; Hemorrhage; Humans; Hypertension; Male; Prospective Studies; Risk Factors; Stroke; Transcatheter Aortic Valve Replacement; Treatment Outcome

It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear.. We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement.. A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%];. In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research.. URL: https://www.. gov. Unique identifier: NCT03284827.

Topics: Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Humans; Platelet Aggregation Inhibitors; Pyridines; Risk Factors; Thiazoles; Thromboembolism; Thrombosis; Transcatheter Aortic Valve Replacement; Treatment Outcome

Optimal antithrombotic strategy following transcatheter aortic valve replacement (TAVR) is still unknown. We hypothesised that the direct factor Xa inhibitor edoxaban can potentially prevent subclinical leaflet thrombosis and cerebral embolisation compared with conventional dual antiplatelet therapy (DAPT) in patients undergoing TAVR.. The ADAPT-TAVR trial is an international, multicentre, randomised, open-label, superiority trial comparing edoxaban-based strategy and DAPT strategy in patients without an indication for oral anticoagulation who underwent successful TAVR. A total of 220 patients are randomised (1:1 ratio), 1-7 days after successful TAVR, to receive either edoxaban (60 mg daily or 30 mg daily if patients had dose-reduction criteria) or DAPT using aspirin (100 mg daily) plus clopidogrel (75 mg daily) for 6 months. The primary endpoint was an incidence of leaflet thrombosis on four-dimensional, volume-rendered cardiac CT imaging at 6 months post-TAVR. The key secondary endpoints were the number of new lesions and new lesion volume on brain diffusion-weighted MRI and the changes in neurological and neurocognitive function assessment between immediate post-TAVR and 6 months of study drug administration. Detailed clinical information on thromboembolic and bleeding events were also assessed.. Ethic approval has been obtained from the Ethics Committee/Institutional Review Board of Asan Medical Center (approval number: 2017-1317) and this trial is also approved by National Institute of Food and Drug Safety Evaluation of Republic of Korea (approval number: 31511). Results of this study will be disseminated in scientific publication in reputed journals.. NCT03284827.

Topics: Aortic Valve; Aortic Valve Stenosis; Humans; Platelet Aggregation Inhibitors; Pyridines; Republic of Korea; Risk Factors; Thiazoles; Thrombosis; Transcatheter Aortic Valve Replacement; Treatment Outcome

Transcatheter aortic valve implantation, also called transcatheter aortic valve replacement (TAVR), is the treatment of choice for patients with severe aortic stenosis and intermediate to high operative risk. A significant portion of TAVR patients have atrial fibrillation (AF) requiring chronic oral anticoagulation. In moderate- to high-risk AF patients, the direct factor Xa inhibitor edoxaban is noninferior to vitamin K antagonists (VKAs) for prevention of stroke or systemic embolism with less bleeding and cardiovascular deaths. ENVISAGE-TAVI AF (NCT02943785) is a multinational, multicenter, prospective, randomized, open-label, blinded end point evaluation study comparing edoxaban to VKA-based therapy in approximately 1,400 patients with an indication for chronic oral anticoagulation after successful transfemoral TAVR. The coprimary end points are to assess the differential effects of the 2 treatments (a) on net adverse clinical events (the composite of all-cause death, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, and major bleeding events) and (b) on major bleeding. Twelve hours to 5 days after successful TAVR, patients will be randomized to 60 mg daily oral edoxaban or any VKA (international normalized ratio: 2.0-3.0 or 1.6-2.6 [numbers inclusive] in Japan if age ≥ 70 years). Antiplatelet therapy may be administered per physician's discretion. Randomization will be stratified by edoxaban dose reduction (per local label). Treatment duration will be up to 36 months. The study is powered (80%) to detect noninferiority (margin for the hazard ratio: 1.38) for the composite primary end points, followed by superiority testing.

Topics: Aortic Valve; Aortic Valve Stenosis; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Prospective Studies; Pyridines; Standard of Care; Thiazoles; Thromboembolism; Thrombolytic Therapy; Transcatheter Aortic Valve Replacement; Treatment Outcome

Thromboembolic events remain clinically unresolved after transcatheter aortic valve implantation (TAVI). The use of direct oral anticoagulant (DOAC) to reduce thrombosis associated with TAVI remains controversial. This study aimed at investigating the periprocedural change in blood coagulation and thrombolysis parameters in 199 patients undergoing transfemoral TAVI. Prothrombin activation fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), soluble fibrin monomer complex (SFMC), and fibrin/fibrinogen degradation product (FDP) levels were measured before and 1 hour after TAVI and 1, 2, and 7 days postoperatively. Of the 199 patients, 49 were treated with DOAC (apixaban in 32, edoxaban in 10, and rivaroxaban in 7). The F1 + 2 and TAT levels immediately increased 1 hour after TAVI and then gradually decreased in both groups. The SFMC level also significantly increased with a peak on day 1. The FDP level gradually increased, peaking on day 2. The values of F1 + 2, TAT, SFMC, and FDP in patients who used DOAC were significantly lower than those who did not use DOAC at 1 hour after TAVI in F1 + 2 (600 [452 to 765] vs 1055 [812 to 1340] pmol/L; p < 0.001), TAT (21.4 [16.2 to 37.0] vs 38.7 [26.4 to 58.7] μg/mL; p < 0.001) and on day 1 in SFMC (18.2 [9.4 to 57.9] vs 113.4 [70.9 to 157.3] μg/mL; p < 0.001) and day 2 in FDP (6.0 [4.7 to 10.0] vs 12.6 [8.2 to 17.4] μg/mL; p < 0.001). Ischemic stroke within 30 days after TAVI occurred in 3 patients (1.5%), who were not treated with DOAC. Coagulation cascade activation was observed after TAVI. DOAC could reduce transient hypercoagulation following TAVI.

Topics: Aged, 80 and over; Antithrombin III; Aortic Valve Stenosis; Blood Coagulation; Cohort Studies; Factor Xa Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Peptide Fragments; Peptide Hydrolases; Prothrombin; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thrombosis; Transcatheter Aortic Valve Replacement