Post-TAVR Anti-thrombotics: Issues Unresolved
August 7th, Highlight Session of TCTAP & AP VALVES 2020 VIRTUAL
George D. Dangas, MD presented a lecture on the issue related to post-transcatheter aortic valve replacement (TAVR) antithrombotic regimens at the highlight Valve session of TCTAP & AP VALVES 2020 VIRTUAL. He highlighted that the proposed mechanisms causing prosthetic valve thrombosis are likely multifactorial, including factors related to valve surface, hemodynamic and hemostatic factors. Valve thrombosis also affects surgical bioprosthesis but might be previously less well recognized in view of the lack of good imaging modality, e.g. 4D CT, decades ago.
Studies showed that subclinical leaflet thrombosis, also known as Hypo-Attenuating Leaflet Thickening (HALT), comes and goes with time and therefore its natural history is not completely understood. It occurs in transcatheter heart valves, either balloon-expandable or self-expandable, as well as surgical heart valves. Its association with transvalvular pressure gradient is weak and therefore the diagnosis relies on dedicated CT imaging. The significance of HALT relating to valve durability, or even its association with stroke has not actually been established. Anti-coagulation, however, was shown to be able to prevent or even treat HALT or reduced leaflet motion. This gave rise to a few trials evaluating different anti-thrombotic regimens to be used during post-TAVR period.
The latest guidelines recommended the use of dual anti-platelets therapy (DAPT), mainly aspirin plus clopidogrel, as the post-TAVR anti-thrombotic regimen. However, a few small studies showed that clopidogrel did not offer extra ischemic benefit on top of aspirin but instead caused more bleeding events.
Low-dose rivaroxaban (10mg daily) was evaluated in the GALILEO Trial for prevention of subclinical leaflet thrombosis but disappointingly both the thromboembolic events and mortality rates were higher in the rivaroxaban arm compared to anti-platelet arm, in addition to the expectedly higher bleeding rate. Paradoxically, the GALILEO-4D sub-study demonstrated that rivaroxaban was effective in preventing subclinical reduced leaflet motion, as shown on 4D-CT at three months after TAVR. However, this apparent benefit at leaflet level was not translated to better clinical effects as shown in the main GALILEO study.
As evaluated in the POPULAR TAVI trial, in patients having atrial fibrillation who had undergone TAVR, oral anti-coagulation alone was shown to result in less bleeding without sacrificing ischemic endpoint when compared to oral anti-coagulation plus clopidogrel. There are also ongoing randomized studies e.g. ATLANTIS, ENVISAGE-TAVI AF and ADAPT-TAVR, evaluating other Non-vitamin K Oral Anti-coagulants (NOAC) for post-TAVR anti-thrombotic use in patients with or without indication for long-term anti-coagulation.
In the real-world setting, anti-thrombotic regimen used post-TAVR could be very variable. The regimen ranges from no anti-thrombotic to triple anti-thrombotics therapy. Additional evidences and appropriate guideline recommendations are urgently required.
When asked about any personal recommendation on the post-TAVR regimen after weighing all the currently available evidences, Dr. Dangas said for patients with no concurrent indications for anti-coagulation, there is not enough good evidence to act against the current guideline recommendation of using DAPT for 3-6 months, but there is a strong doubt on the need for clopidogrel. If patients need anti-coagulations for atrial fibrillation, anti-coagulation would be his choice of post-TAVR anti-thrombotic. Whether to add on anti-platelet depends on whether the patient has other co-existing indications like history of peripheral arterial disease, coronary stenting, etc.
Editor: Anthony Yiu Tung Wong, MD (Queen Mary Hospital, Hong Kong, China)