Key result
Three months of DOAC therapy after successful TAVI reduced subclinical leaflet thickening (HALT) at 3 months (12% vs 32% with SAPT alone), but the effect was not sustained at 12 months (28% vs 32%), and all-cause mortality, stroke, or major/life-threatening bleeding occurred more often with DOAC (8.2% vs 2.3%).
Why the trial?
Hypoattenuated leaflet thickening appears on CT in a substantial minority of TAVI recipients, with unclear clinical significance and no established prevention strategy. NOTION-4 asked whether a three-month DOAC course after TAVI durably prevents subclinical leaflet thrombosis.
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?
| Outcome | DOAC 3m | SAPT |
|---|---|---|
| HALT prevalence at 12 months | 28.3% | 32.2% |
| Primary · RD −3.9% (95% CI −14.4% to 6.6%); p=0.54 — superiority not met; among patients with available CT | ||
| HALT prevalence at 3 months | 12.1% | 31.8% |
| Secondary · on-treatment reduction was not sustained after DOAC discontinuation | ||
Safety
All-cause death, stroke, or major/life-threatening bleeding at 12 months was 8.2% vs 2.3% (RD 5.9%; 95% CI 1.2% to 10.6%) — higher with DOAC-3m.
Design limitations
HALT is a surrogate imaging endpoint that the abstract notes only might be associated with thromboembolic events, and the 12-month primary analysis included only patients with available CT scans.
Statistical certainty
The excess of clinical events with DOAC-3m rests on few events in a modest sample; per-arm counts are not reported.
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?
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
Short-term DOAC therapy after TAVR temporarily reduces subclinical leaflet thrombosis but does not provide sustained benefit at 1 year and increases the risk of adverse clinical events.
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Captured external expert commentary on this trial, strongest first. Original sources are linked where available.
NOTION-4 is described as a study on subclinical leaflet thrombosis after transcatheter aortic valve implantation, presented by Troels Højsgaard Jørgensen.
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“Anticoagulation after TAVI reduced subclinical leaflet thrombosis (HALT) without proven clinical benefit. In NOTION-4, the effect faded after stopping the drug and came with a signal of more death, stroke, or bleeding, so aspirin remains the guideline standard.”
Short-term DOAC after TAVI increases clinical events; reinforces guidelines against routine anticoagulation in patients without other indications.
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).
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Jørgensen et al. (2026) conducted an RCT in Transcatheter aortic valve replacement (TAVR) (n=352). 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).
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