Bivalirudin in TAVI patients for the reduction of thromboembolic events: Rationale and design of the BIVITAL trial

Transcatheter Aortic Valve Implantation (TAVI) is a main treatment for Aortic Valve Stenosis (AS). Randomized clinical trials had proven that TAVI was significantly advanced to Surgical Valve Replacement (SAVR), despite of which, there are still room for further improvements of TAVI in the safety and clinical effects. Thrombosis is a common complication after TAVI, including valve thrombosis, subclinical valve thrombosis, myocardial infarction, myocardial injury, stroke and micro embolism of brain, significantly impair prognosis of patients. Using unfractionated heparin (UFH) for anticoagulation during TAVI was a conventional strategy. However, lots of studies in Percutaneous Coronary Intervention (PCI) showed the incidence of postoperative myocardial infarction and ischemic stroke is noninferior to UFH in use of Bivalirudin, a direct thrombin inhibitor, as an anticoagulant. BRAVO-3 study indicated that the rate of myocardial infarction within 48 hours was significantly lower in Bivalirudin group than UFH group (0% vs. 1.3%, p=0.03). In previous PCI studies, there is no standard criteria of using bivalirudin. A study limit bivalirudin using time in 4-12 hours after PCI resulting in slightly lower incidence of stent thrombosis than the UFH group. Additionally, no studies refined thrombosis into asymptomatic events including subclinical leaflet thrombosis, brain micro embolism and myocardial injury, which is not only with higher incidence in patients, but also capable to predict adverse prognosis. Therefore, we speculate that the rational use of Bivalirudin during TAVI procedure may reduce the risk of thrombosis compared with UFH in patients with aortic valve stenosis in China. The BIVITAL trial is the first prospective, masked, randomized study of Bivalirudin versus UFH in Chinese TAVI patient. The BIVITAL trial uses 7 days or before discharging thromboembolic events as primary endpoint, including valve thrombosis, subclinical leaflet thrombosis (Hypo attenuated leaflet thickening, HALT or reduced leaflet motion, RELM), myocardial infarction, myocardial injury, stroke, transient ischemic attacks (TIA), the number of new brain embolisms with average volume >205 mm3 more than 5. Safety endpoint are 7 days or before discharge any bleeding or hemoglobin levels dropping more than 2.0 g/dl and all-cause mortality. We intend to recruit AS patient planning to receive transfemoral (TF) TAVI procedure, randomized into Bivalirudin group and UFH group in 1:1 fashion. By outcome comparison of two groups, we intend to prove bivalirudin can reduce thromboembolic events.