BACKGROUND Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. METHODS We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. RESULTS After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 personyears, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). CONCLUSIONS In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.

BACKGROUNDSubclinical leaflet thickening and reduced leaflet motion of bioprosthetic aortic valves have been documented by four-dimensional computed tomography (CT). Whether anticoagulation can reduce these phenomena after transcatheter aortic-valve replacement (TAVR) is not known. METHODSIn a substudy of a large randomized trial, we randomly assigned patients who had undergone successful TAVR and who did not have an indication for long-term anticoagulation to a rivaroxaban-based antithrombotic strategy (rivaroxaban [10 mg] plus aspirin [75 to 100 mg] once daily) or an antiplatelet-based strategy (clopidogrel [75 mg] plus aspirin [75 to 100 mg] once daily). Patients underwent evaluation by four-dimensional CT at a mean (±SD) of 90±15 days after randomization. The primary end point was the percentage of patients with at least one prosthetic valve leaflet with grade 3 or higher motion reduction (i.e., involving >50% of the leaflet). Leaflet thickening was also assessed. RESULTSA total of 231 patients were enrolled. At least one prosthetic valve leaflet with grade 3 or higher motion reduction was found in 2 of 97 patients (2.1%) who had scans that could be evaluated in the rivaroxaban group, as compared with 11 of 101 (10.9%) in the antiplatelet group (difference, −8.8 percentage points; 95% confidence interval [CI], −16.5 to −1.9; P = 0.01). Thickening of at least one leaflet was observed in 12 of 97 patients (12.4%) in the rivaroxaban group and in 33 of 102 (32.4%) in the antiplatelet group (difference, −20.0 percentage points; 95% CI, −30.9 to −8.5). In the main trial, the risk of death or thromboembolic events and the risk of life-threatening, disabling, or major bleeding were higher with rivaroxaban (hazard ratios of 1.35 and 1.50, respectively). CONCLUSIONSIn a substudy of a trial involving patients without an indication for long-term anticoagulation who had undergone successful TAVR, a rivaroxaban-based antithrombotic strategy was more effective than an antiplatelet-based strategy in preventing subclinical leafletmotion abnormalities. However, in the main trial, the rivaroxaban-based strategy was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than the antiplatelet-based strategy. (Funded by Bayer; GALILEO-4D ClinicalTrials.gov number, NCT02833948.

Summary. Background and objective: Several studies have suggested that thrombin-activatable fibrinolysis inhibitor (TAFI) levels are associated with the risk of arterial thrombosis, but results have been contradictory. We studied functional TAFI levels and TAFI gene polymorphisms in 124 patients with a recent ischemic stroke and 125 age-and sex-matched controls to establish the role of TAFI in ischemic stroke. Methods and results: Functional TAFI levels, defined as TAFI-related retardation (RT), the difference in clot lysis time (LT) in the absence or presence of a specific activated TAFI inhibitor (potato carboxypeptidase inhibitor [PCI]), were higher in patients than controls (19.5 ± 4.2 vs. 17.7 ± 3.7 min, P < 0.005). Clot LTs in the presence of PCI, which were independent of TAFI, were also increased in ischemic stroke patients. This indicates that in these patients fibrinolysis is impaired not only by high TAFI levels, but also by other mechanisms. Individuals with functional TAFI levels in the highest quartile had an increased risk of ischemic stroke compared with the lowest quartile [odds ratio (OR) 4.0, 95% confidence interval (CI): 1.6-9.8]. In an unselected group of 36 of the 125 stroke patients functional TAFI levels were also measured at 3 months, and were persistently high. This indicates that increased functional TAFI levels after stroke are not caused by an acute phase reaction. No difference was found between patients and controls with respect to TAFI genotype distribution. Conclusions: Increased functional TAFI levels, resulting in decreased fibrinolysis, are associated with an increased risk of ischemic stroke.