- Design
- randomised controlled trial, 1:1, open comparison of two antithrombotic strategies, powered for superiority (NOTION-4)
- Population
- 347 analysed patients without an indication for oral anticoagulation shortly after successful TAVR
- Primary outcome
- prevalence of hypoattenuated leaflet thickening on cardiac CT at 12 months
- Effect
- 28.3% with 3 months of DOAC vs 32.2% with antiplatelet therapy; risk difference -3.9% (95% CI -14.4 to 6.6), P=0.54; at 3 months 12.1% vs 31.8%
NOTION-4 randomised patients without an independent indication for oral anticoagulation shortly after successful transcatheter aortic valve replacement to lifelong single antiplatelet therapy or three months of a direct oral anticoagulant followed by lifelong single antiplatelet therapy. Of 352 randomised, 347 were analysed: 176 antiplatelet, 171 anticoagulant. The primary endpoint was the prevalence of hypoattenuated leaflet thickening on cardiac CT at twelve months.
While the anticoagulant was running, it worked: leaflet thickening at three months was 12.1% against 31.8%. Nine months after it stopped, the difference had disappeared. At twelve months thickening was present in 28.3% of the anticoagulant group and 32.2% of the antiplatelet group, a risk difference of -3.9% (95% CI -14.4 to 6.6), P=0.54. The trial was powered for superiority and did not find it.
The safety figures point the other way. The combined risk of death from any cause, stroke or major or life-threatening bleeding at twelve months was 2.3% with antiplatelet therapy alone and 8.2% with the anticoagulant strategy, a risk difference of 5.9% (95% CI 1.2 to 10.6). That was not the primary endpoint and the trial was not powered for it, so the size of the harm is uncertain; the direction is not, and the interval excludes zero.
The practical reading is straightforward. Leaflet thickening is a CT finding, not an outcome, and suppressing it temporarily with anticoagulation does not keep it suppressed and does not appear to be free. Do not add a DOAC after TAVI to prevent leaflet thrombosis in a patient who has no other reason to be anticoagulated. Where the patient does have atrial fibrillation or another indication, none of this applies: that decision is made on the indication.
- Do not start a DOAC after TAVI purely to prevent or treat asymptomatic leaflet thickening
- Keep anticoagulation decisions after TAVI tied to a conventional indication, most often atrial fibrillation
- Treat hypoattenuated leaflet thickening on a routine CT as a finding to follow, not an automatic trigger for anticoagulation
- Quote the bleeding side of the conversation honestly: the composite of death, stroke or major bleeding was about three and a half times higher in the anticoagulant arm
- Where routine post-TAVI CT is not done, this trial gives no reason to start doing it
The statistics, in plain English
The primary result is a confidence interval running from -14.4% to +6.6%: it includes zero and both directions, so this is a genuinely null result rather than a trial that narrowly missed. The three-month difference was real but temporary, which is the point of the paper, and it illustrates why a surrogate measured during treatment can mislead about what happens after it. The safety composite ran the other way with an interval of 1.2% to 10.6% that excludes zero, but it was a secondary endpoint in a trial of 347 patients, so read it as a clear warning about direction and an unreliable estimate of size.
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