August 30, 2026
Short-Term Anticoagulant Therapy and Subclinical Leaflet Thickening in Transcatheter Aortic Valves:The NOTION-4 Trial
Why the study?
Subclinical leaflet thrombosis after TAVR is common and may be associated with thromboembolic events, but optimal antithrombotic strategies to prevent HALT are unclear.
Does 3 months of DOAC therapy followed by SAPT reduce HALT prevalence at 12 months in TAVR patients without an indication for oral anticoagulation compared to lifelong SAPT?
Key Points
- To determine whether a 3-month course of direct oral anticoagulant therapy prevents subclinical hypoattenuated leaflet thickening compared with single antiplatelet therapy after transcatheter aortic valve replacement.
- Randomized, superiority clinical trial (NOTION-4, NCT06449469) enrolling patients without oral anticoagulation indications following successful transcatheter aortic valve replacement.
- A total of 352 patients were randomized 1:1 to either lifelong single antiplatelet therapy (SAPT, n=176) or 3 months of direct oral anticoagulant therapy followed by lifelong SAPT (DOAC-3m, n=171), with cardiac computed tomography follow-up at 3 and 12 months.
- At 12 months, hypoattenuated leaflet thickening occurred in 32.2% of SAPT patients versus 28.3% of DOAC-3m patients (risk difference: -3.9%; 95% CI: -14.4% to 6.6%; P = 0.54).
- At 3 months, hypoattenuated leaflet thickening was present in 31.8% of patients receiving SAPT compared with 12.1% receiving DOAC-3m.
- The composite safety outcome of all-cause mortality, stroke, or major/life-threatening bleeding at 12 months occurred in 2.3% of the SAPT group versus 8.2% of the DOAC-3m group (risk difference: 5.9%; 95% CI: 1.2% to 10.6%).
Study Design
Type
RCT (n=347)
Randomization
1:1
Structured PICO
Does 3 months of DOAC therapy followed by SAPT reduce HALT prevalence at 12 months in TAVR patients without an indication for oral anticoagulation compared to lifelong SAPT?
P
Population
347 patients without an indication for oral anticoagulation shortly after successful TAVR, followed for 12 months.
I
Intervention
3 months of direct oral anticoagulant (DOAC) therapy followed by lifelong single antiplatelet therapy (SAPT)
C
Comparator
Lifelong single antiplatelet therapy (SAPT)
O
Outcome
Hypoattenuated leaflet thickening (HALT) prevalence at 12 monthssurrogate
Main Result
Effect estimate: risk difference -3.9% (95% CI -14.4% to 6.6%)
Absolute Event Rate: 28.3% vs 32.2%
p-value: p=0.54
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Although the trial's precisions at 12 months do not allow us to confirm or rule out a modest, sustained effect on HALT in the [DOAC] group, the serial cardiac CT scans suggest that the impact of short-term DOAC therapy on HALT is not permanent. Moreover, because the short-term reduction in HALT with [three-month DOAC] was not associated with a clinical benefit – and clinical events occurred numerically more frequently in the DOAC group – our findings support current guidelines that recommend against the routine use of DOACs after TAVR in patients without another indication for oral anticoagulation.”
DTDr. Troels Hojsgaard Jørgensen
“Together, these findings support the current guidelines recommendation against routine use of DOAC after TAVI in patients without any other indication for oral anticoagulant therapy.”
“With ACASA-TAVI and NOTION-4 now reported, the DOAC-TAVR literature as a whole is still 'overall non-conclusive'.”
Implication
A 3-month course of DOAC after TAVR reduces subclinical leaflet thrombosis at 3 months, but this benefit is lost by 12 months and is associated with a higher risk of adverse clinical events including bleeding.
Abstract
BACKGROUND: Following transcatheter aortic valve replacement (TAVR), subclinical leaflet thrombosis-visualized on cardiac computed tomography (CT) as hypoattenuated leaflet thickening (HALT)-is common and might be associated with thromboembolic events. OBJECTIVES: The NOTION-4 trial investigates different antithrombotic treatment strategies for the prevention of HALT. METHODS: NOTION-4 was a randomized controlled trial enrolling patients without an indication for oral anticoagulation shortly after successful TAVR. Patients were randomized to lifelong single antiplatelet therapy (SAPT) or 3 months of direct oral anticoagulant (DOAC) therapy followed by lifelong SAPT (DOAC-3m). The primary endpoint was HALT prevalence at 12 months. The trial was powered for superiority of the experimental strategy. RESULTS: Of 352 patients randomized 1:1, 5 were screen failures or withdrew consent, leaving 176 in the SAPT group and 171 in the DOAC-3m group. At 3 months, HALT was observed in 31.8% of patients receiving SAPT compared with 12.1% of those receiving DOAC-3m. At 1 year, HALT occurred in 32.2% of SAPT patients and 28.3% of DOAC-3m patients with available CT scans (risk difference: -3.9%; 95% CI: -14.4% to 6.6%; P = 0.54). The combined risk of all-cause mortality, stroke, or major/life-threatening bleeding at 12 months was 2.3% in the SAPT group vs 8.2% in the DOAC-3m group (risk difference: 5.9%; 95% CI: 1.2% to 10.6%). CONCLUSIONS: Among TAVR patients without an indication for oral anticoagulation, 3 months of DOAC therapy significantly reduced the prevalence of HALT at 3 months compared with SAPT; however, this effect was attenuated by 9 months after discontinuation of DOAC therapy. (The Nordic Aortic Valve Intervention Trial 4 [NOTION-4]; NCT06449469).
Discussion
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Cite This Study
NOTION-4 Investigators (2026) conducted an RCT in Patients without an indication for oral anticoagulation shortly after successful TAVR (n=347). 3 months of direct oral anticoagulant (DOAC) therapy followed by lifelong SAPT vs. Lifelong single antiplatelet therapy (SAPT) was evaluated on HALT prevalence at 12 months (risk difference -3.9%, 95% CI -14.4% to 6.6%, p=0.54).