Table 3.
Ongoing trials with novel oral anticoagulants in patients post-TAVI.
| POPular-TAVI | ATLANTIS | ENVISAGE-TAVI AF | AUREA | AVATAR | |
|---|---|---|---|---|---|
| (ClinicalTrials. gov) Identification | NCT02247128 | NCT02664649 | NCT02943785 | NCT01642134 | NCT02735902 |
| Study Design | Multicentre, open-label, randomised | Multicentre, open-label, randomised, phase IIIb | Multicentre, open-label, randomised, phase IIIb | Multicentre, randomised, phase IV | Multicentre, open-label, randomised |
| Patient Cohort | No need for long-term OAC | Successful TAVI without consideration of previous antithrombotic treatment | Successful TAVI. Patients have AF and an ongoing indication for OAC. | Patients with successful TAVI procedure not under OAC treatment. | Successful TAVI procedure and patient receiving VKA prior to procedure |
| Experimental Drug | Cohort A: 75 mg clopidogrel OD and <100 mg aspirin OD. Cohort B: 75 mg clopidogrel and OAC. | 5 mg apixaban. 2.5 mg apixaban, if the patient has 2 or more factors a | Edoxaban-based regimen 60 mg and 30 mg tablet OD and 15 mg tablet for transitioning at end of treatment. Antiplatelet therapy (if prescribed): aspirin 75–100 mg OD or clopidogrel 75 mg OD | VKA (acenocumarol) | VKA (target INR 2–3) |
| Comparator | Cohort A: <100 mg aspirin. Cohort B: OAC. | VKA if AF or antiplatelet therapy if sinus rhythm | VKA-based regimen oral VKA tablets as selected and provided by the site. (Target INR 2–3) | DAPT with 100 mg aspirin and 75 mg clopidogrel | 75–100 mg aspirin and VKA (VKA corresponding to anticoagulation the patient was receiving prior to TAVI, monitored and adapted to current recommendations) |
| Primary Outcome | Lack of bleeding complications as per BARC definition 1 year post-TAVI. Co-primary outcome defined as freedom of non-procedure-related bleeding complications at 1 year post-TAVI. | Composite of death, MI, stroke, peripheral embolism, intracardiac or bioprosthesis thrombus, any episode of DVT or PE, major bleeding (up to 13 months) | Number of participants experiencing any of these factors b (within 36 months). Number of participants experiencing major bleeding (within 36 months). | Cerebral thromboembolism by the detection of cerebral infarction by MRI within the first 3 months post-TAVI (within 3 months). | Composite of all-cause death, MI, stroke, valve thrombosis and haemorrhage >2 as defined by the VARC 2. (within 12 months). |
| Duration | Aspirin for at least 12 months, with a lifelong recommendation. Clopidogrel discontinued after 90 days in both cohorts | 12 months | VKA continued until efficacy endpoints are reached or up to 36 months post-randomisation. Aspirin or clopidogrel discontinued after 90 days. Patients with stenting post-TAVI continue aspirin or clopidogrel up to 12 months, DAPT allowed for 1 month. | 3 months | 12 months |
| Estimated Enrolment | 1000 | 1509 | 1400 | 124 | 170 |
OAC: oral anticoagulation; DAPT: dual antiplatelet therapy; VARC: valve academic research consortium; BARC: bleeding academic research consortium; INR: international normalised ratio; MI: Myocardial infarction; PE: pulmonary embolism; DVT: deep vein thrombosis; MRI: Magnetic resonance imaging [75,76,77,78,79,80]. a age >80years, body weight <60 kg, serum creatinine >1.5 mg/dL/; b all-cause death, MI, ischaemic stroke, valve thrombosis, and major bleeding.