rivaroxaban and Aortic-Valve-Stenosis

Optimal antithrombotic treatment after transcatheter aortic valve replacement (TAVR) is unknown and determined empirically. The direct factor Xa inhibitor rivaroxaban may potentially reduce TAVR-related thrombotic complications and premature valve failure.. GALILEO is an international, randomized, open-label, event-driven, phase III trial in more than 1,520 patients without an indication for oral anticoagulation who underwent a successful TAVR (ClinicalTrials.govNCT02556203). Patients are randomized (1:1 ratio), 1 to 7days after a successful TAVR, to either a rivaroxaban-based strategy or an antiplatelet-based strategy. In the experimental arm, subjects receive rivaroxaban (10mg once daily [OD]) plus acetylsalicylic acid (ASA, 75-100mg OD) for 90days followed by rivaroxaban alone. In the control arm, subjects receive clopidogrel (75mg OD) plus ASA (as above) for 90days followed by ASA alone. In case new-onset atrial fibrillation occurs after randomization, full oral anticoagulation will be implemented with maintenance of the original treatment assignment. The primary efficacy end point is the composite of all-cause death, stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism, deep venous thrombosis, and systemic embolism. The primary safety end point is the composite of life-threatening, disabling, and major bleeding, according to the Valve Academic Research Consortium definitions.. GALILEO will test the hypothesis that a rivaroxaban-based antithrombotic strategy reduces the risk of thromboembolic complications post-TAVR with an acceptable risk of bleeding compared with the currently recommended antiplatelet therapy-based strategy in subjects without need of chronic oral anticoagulation.

Topics: Aortic Valve Stenosis; Aspirin; Cardiovascular Diseases; Cause of Death; Clopidogrel; Drug Therapy, Combination; Embolism; Factor Xa Inhibitors; Heart Valve Diseases; Humans; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Care; Pulmonary Embolism; Rivaroxaban; Stroke; Thrombosis; Ticlopidine; Transcatheter Aortic Valve Replacement; Venous Thrombosis

To compare the characteristics and outcomes of patients with atrial fibrillation (AF) and aortic stenosis (AS) with patients with AF with mitral regurgitation (MR) or aortic regurgitation (AR) and patients without significant valve disease (no SVD).. Using Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) data, we analysed efficacy and safety outcomes, adjusting hazard ratios (HRs) for potential confounders using Cox regression analysis.. Among 14 119 intention-to-treat ROCKET AF trial patients, a trial that excluded patients with mitral stenosis or artificial valve prosthesis, 214 had AS with or without other valve abnormalities, 1726 had MR or AR and 12 179 had no SVD. After adjusting for prognostic factors, the composite of stroke, systemic embolism or vascular death increased approximately twofold in patients with AS (AS 10.84, MR or AR 4.54 and no SVD 4.31 events per 100 patient-years, p=0.0001). All-cause death also significantly increased (AS 11.22, MR or AR 4.90 and no SVD 4.39 events per 100 patient-years, p=0.0003). Major bleeding occurred more frequently in AS (adjusted HR 1.61, confidence intervals (CI) 1.03 to 2.49, p<0.05) and MR or AR (HR 1.30, 1.07 to 1.57, p<0.01) than in no SVD, but there was no difference between AS and MR or AR (HR 1.24, 0.78 to 1.97). The relative efficacy of rivaroxaban versus warfarin was consistent among patients with and without valvular disease. Rivaroxaban was associated with higher rates of major bleeding than warfarin in patients with MR or AR (HR 1.63, 1.15 to 2.31).. We found that patients with AF and AS on oral anticoagulants may have distinctly different efficacy and safety outcomes than patients with MR or AR or no SVD.. NCT00403767; Post-results.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Aortic Valve Insufficiency; Aortic Valve Stenosis; Atrial Fibrillation; Drug Administration Schedule; Female; Humans; Male; Mitral Valve Insufficiency; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

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

Topics: Aortic Valve; Aortic Valve Stenosis; Humans; Rivaroxaban; Transcatheter Aortic Valve Replacement

Topics: Aortic Valve; Aortic Valve Stenosis; Humans; Rivaroxaban; Transcatheter Aortic Valve Replacement

Topics: Administration, Oral; Aortic Valve; Aortic Valve Stenosis; Early Termination of Clinical Trials; Factor Xa Inhibitors; Fibrinolytic Agents; Heart Valve Prosthesis; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Thrombosis; Transcatheter Aortic Valve Replacement; Treatment Outcome

Treatment with non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran (a direct thrombin inhibitor) or rivaroxaban (a direct inhibitor of factor [F] Xa) attenuates atherosclerotic plaque progression in hypercholesterolemic mice.. To evaluate the effect of NOACs application on the expression of coagulation proteins in loco within stenotic aortic valves and in valve interstitial cells (VICs) from patients with severe aortic stenosis (AS).. Primary cultures of VICs obtained from 90 patients undergoing aortic valve replacement were stimulated with TNF-α (50 ng/mL) and pre-treated with rivaroxaban (1 and 10 ng/mL) or dabigatran (25 and 250 ng/mL). The expression of coagulation proteins was analyzed by immunofluorescence. Cytokine levels were measured by ELISA.. FX, FXa, FVII, thrombin and PAR1/2 were present in loco within human aortic stenotic valves. Cultured VICs exhibited constant expression of FX, TF, PAR1/2. Exposure of VICs to TNF-α caused the upregulated expression of TF, PAR1/2 and induced expression of thrombin, FVII and FXa. FX was expressed by 80% of VICs, regardless of stimulation. Cultured VICs were able to synthesize metalloproteinases 1-3, IL-6, IL-32, IL-34, osteopontin and osteocalcin, the levels of which increased under TNF-α stimulation. NOACs added to culture inhibited coagulation factor and PAR1/2 expression. Moreover, NOACs down-regulated VIC-derived proteins responsible for valve calcification and extracellular matrix remodeling.. NOACs at therapeutic concentrations may inhibit the effects of FXa and thrombin at in vitro level. It might be speculated that long-term treatment with rivaroxaban or dabigatran could attenuate the progression of AS in humans.

Topics: Aged; Antithrombins; Aortic Valve; Aortic Valve Stenosis; Blood Coagulation Factors; Cells, Cultured; Dabigatran; Factor Xa Inhibitors; Female; Humans; Inflammation Mediators; Male; Middle Aged; Rivaroxaban; Severity of Illness Index; Signal Transduction

Topics: Aortic Valve Stenosis; Heart Valve Prosthesis; Humans; Rivaroxaban; Transcatheter Aortic Valve Replacement

Topics: Aortic Valve Stenosis; Heart Valve Prosthesis; Humans; Rivaroxaban; Transcatheter Aortic Valve Replacement

Topics: Aortic Valve Stenosis; Heart Valve Prosthesis; Humans; Rivaroxaban; Transcatheter Aortic Valve Replacement

Topics: Aortic Valve Stenosis; Heart Valve Prosthesis; Humans; Rivaroxaban; Transcatheter Aortic Valve Replacement

Topics: Aortic Valve Stenosis; Heart Valve Prosthesis; Humans; Rivaroxaban; Transcatheter Aortic Valve Replacement

There is increasing evidence that bioprosthetic valve thrombosis (BPVT) is more common than previously thought. However, there are very few cases describing the occurrence of BPVT on therapeutic anticoagulation, and no previous cases are available stating the occurrence of BPVT on direct oral anticoagulant therapy. We describe the case of surgically managed aortic BPVT that was diagnosed while the patient was on rivaroxaban.

Topics: Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Bioprosthesis; Echocardiography, Transesophageal; Factor Xa Inhibitors; Female; Heart Diseases; Heart Valve Prosthesis; Heart Ventricles; Humans; Prosthesis Failure; Rivaroxaban; Thrombosis

Vitamin K antagonists, such as warfarin, are known to promote arterial calcification through blockade of gamma-carboxylation of Matrix-Gla-Protein. It is currently unknown whether other oral anticoagulants such as direct inhibitors of Factor Xa can have protective effects on the progression of aortic valve calcification.. To compare the effect of warfarin and rivaroxaban on the progression of aortic valve calcification in atherosclerotic mice.. 42 ApoE-/- mice fed with Western-type Diet (WTD) were randomized to treatment with warfarin (n = 14), rivaroxaban (n = 14) or control (n = 14) for 8 weeks. Histological analyses were performed to quantify the calcification of aortic valve leaflets and the development of atherosclerosis. The analyses showed a significant increase in valve calcification in mice treated with warfarin as compared to WTD alone (P = .025) or rivaroxaban (P = .005), whereas no significant differences were found between rivaroxaban and WTD (P = .35). Quantification of atherosclerosis and intimal calcification was performed on the innominate artery of the mice and no differences were found between the 3 treatments as far as atherogenesis and calcium deposition is concerned. In vitro experiments performed using bovine interstitial valve cells (VIC) showed that treatment with rivaroxaban did not prevent the osteogenic conversion of the cells but reduce the over-expression of COX-2 induced by inflammatory mediators.. We showed that warfarin, but not rivaroxaban, could induce calcific valve degeneration in a mouse model of atherosclerosis. Both the treatments did not significantly affect the progression of atherosclerosis. Overall, these data suggest a safer profile of rivaroxaban on the risk of cardiovascular disease progression.

Topics: Animals; Anticoagulants; Aortic Valve; Aortic Valve Stenosis; Atherosclerosis; Calcinosis; Cattle; Cells, Cultured; Cyclooxygenase 2; Disease Models, Animal; Disease Progression; Factor Xa Inhibitors; Female; Male; Mice, Knockout, ApoE; Risk Assessment; Rivaroxaban; Time Factors; Vascular Calcification; Warfarin

BACKGROUND Although transcatheter aortic valve replacement (TAVR) has become a worldwide and generally accepted treatment of patients with aortic stenosis at high surgical risk, there is a rising concern and debate about the occurrence of transcatheter heart valve (THV) thrombosis and its impact on TAVR outcome. It seems that the incidence of THV thrombosis is higher than first anticipated, but uncertainty remains regarding how to prevent and how to treat it. Hence, there is an urgent need for understanding THV thrombosis and to communicate experiences within the field. CASE REPORT We present a unique case of late occurrence of THV thrombosis that was resolved by switching from clopidogrel to rivaroxaban treatment. CONCLUSIONS As a novel observation, our case demonstrates that THV thrombosis may develop even late after TAVR, and even in such cases may be completely reversed. It also underscores that THV dysfunction should evoke prompt investigation for possible thrombus formation, preferable by multidetector computed tomography. Finally, this case report suggests NOAC as an alternative to warfarin treatment in patients with THV thrombosis.

Topics: Aged; Aortic Valve Stenosis; Factor Xa Inhibitors; Heart Valve Prosthesis; Humans; Male; Rivaroxaban; Thrombosis; Transcatheter Aortic Valve Replacement

Thrombosis of transcatheter aortic valve implantation (TAVI) is an uncommon complication that commonly occurs weeks to months following the procedure. Herein are described the details of a patient who presented with a recurrence of symptoms days after intervention with a bioprosthesis thrombosis that was successfully treated with direct oral anticoagulant (DOAC) therapy and resulted in hemodynamic improvement and resolution of symptoms. Whilst a previous trial of DOAC therapy with mechanical valves was stopped due to elevated events in comparison to warfarin, a TAVI valve may be different, and the rapid onset of action and reduced bleeding risk may be beneficial in this patient group.

Topics: Administration, Oral; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Bioprosthesis; Blood Coagulation; Echocardiography, Three-Dimensional; Echocardiography, Transesophageal; Factor Xa Inhibitors; Heart Valve Prosthesis; Hemodynamics; Humans; Male; Prosthesis Design; Rivaroxaban; Thrombosis; Time Factors; Tomography, X-Ray Computed; Transcatheter Aortic Valve Replacement; Treatment Outcome