NATIONAL HARBOR, MD. – Anticoagulation reduces the risk of leaflet thrombosis at 30 days relative to antiplatelet therapy in low-risk patients undergoing transcatheter aortic valve replacement (TAVR), according to a randomized feasibility study presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute..
At 30 days, oral anticoagulation with warfarin did not appear to be associated with any increased risk of adverse outcomes, including bleeding events, relative to aspirin, according to, the scientific lead for the Structural Heart Disease Program at MedStar Heart & Vascular Institute, Washington.
The rationale for this feasibility study, called, was to evaluate whether anticoagulation after low-risk TAVR reduces the risk of early subclinical leaflet thrombosis, a potential threat to long-term valve survival.
“In the first LRT trial, HALT [hypoattenuated leaflet thickening] was observed in 13.5% of patients on antiplatelet therapy but only 4.8% of those on oral anticoagulation,” Dr. Rogers said.
The two strategies have not been adequately compared, particularly in low-risk patients, according to Dr. Rogers. He noted that current guidelines recommend dual-antiplatelet therapy after TAVR but the oral anticoagulant warfarin after surgical valve replacement, a situation he characterized as a “discrepancy.”
In the multicenter, randomized LRT 2.0 trial, 94 patients undergoing TAVR and meeting prespecified low-risk criteria, such as a Society of Thoracic Surgeons score of 3 or lower, were randomized to warfarin or to aspirin. The study called for an enrollment of 200 patients but was closed early when the Food and Drug Administration approved TAVR for low-risk patients in 2019, causing “enrollment to dry up over night.”
However, an additional registry cohort was included in a separate analysis. This registry cohort consisted of 30 patients who were evaluated for trial inclusion but were found to be inappropriate for randomization because they already had an indication for anticoagulation or had an elevated risk of bleeding. These low-risk TAVR patients were assigned to anticoagulation or antiplatelet therapy as appropriate.
When the randomized groups were compared, the incidence of HALT at 30 days on CT scan was 4.7% among those on warfarin and 16.3% (P = .07) among those taking aspirin. Dr. Rogers believes the near miss for statistical significance was a problem of power, a position supported by the pooled analysis of randomized and registry patients. With the added patients, the difference in HALT did reach significance (3.1% vs. 16.4%; P = .01).
The numerical differences in reduced leaflet motion and hypoattenuated motion favoring anticoagulation trended for significance in the randomized cohort (P = .12) but reached the cusp of significance in the pooled cohort (1.5% vs. 9.4%; P = .052) for both reduced leaflet motion and hypoattenuated motion).
There were no deaths recorded in any treatment arm, whether restricted to the randomized trial or within the pooled cohort. For the pooled cohort, there were more strokes in the aspirin arm (5.4% vs. 1.5%) but Dr. Rogers said that no conclusions could be drawn about relative risk because of the study size and small number of events.
For anticoagulation relative to antiplatelet therapy, respectively, the incidence of new-onset atrial fibrillation (1.5% vs. 1.8%), pacemaker implantation (11.8% vs. 7.1%), major bleeding (1.5% vs. 5.4%), and median length of stay (2.2 vs. 2.4 days) were all similar. The improvements in hemodynamics 30 days after TAVR were substantial and similar in the two groups, according to Dr. Rogers.
Emphasizing that this is a feasibility study, Dr. Rogers cautioned that these data do not necessarily demonstrate that anticoagulation is a better strategy than antiplatelet therapy in low-risk patients after TAVR, but they do associate anticoagulation with a reduced risk of early leaflet thrombosis.
“We fear leaflet thrombosis for the potential that it will negatively impact valve durability, which is particularly important in younger lower-risk patients who might outlive their first valve prosthesis,” Dr. Rogers said.
Panelists at the late-breaking clinical trial session expressed interest in this concept but generally agreed that longer follow-up is needed. This additional follow-up is important for monitoring effect on leaflet thrombosis as well as on the overall impact of these strategies on adverse events.
“We need to see CT scans at later time points because we do not know where this complication comes from. The trigger for leaflet thrombosis might still be there after 30 days,” said Andreas Baumbach, MD, professor of interventional cardiology at the University of Bristol (England). However, he agreed that this is an important line of research, because the potential risk of leaflet thrombosis is “a very important question for us.”
Dr. Rogers reported financial relationships with Edwards Lifesciences and Medtronic.