A blood thinner reduced signs of clot formation on replacement aortic valves compared with aspirin after transcatheter aortic valve implantation, according to a randomized clinical trial published August 30, 2026, in JAMA.
Cardiac CT imaging can detect changes in replacement valve leaflets, including subclinical leaflet thrombosis after TAVI. The image is illustrative and is not an actual scan from the ACASA-TAVI trial.
The ACASA-TAVI trial included 360 adults aged 65 to 80 who underwent transcatheter aortic valve implantation, or TAVI, for severe aortic stenosis. Participants received either a factor Xa inhibitor oral anticoagulant or aspirin alone for 12 months.
At one year, CT scans detected subclinical leaflet thrombosis in 16.2% of patients assigned to anticoagulation compared with 28.6% assigned to aspirin. This corresponds to about a 45% lower relative risk of the imaging abnormality with anticoagulation.
But earlier TAVI trials provide an important warning about how that result should be interpreted. Anticoagulants have previously reduced signs of valve thrombosis without necessarily producing better overall outcomes for patients.
Key Takeaways
- The randomized ACASA-TAVI trial included 360 patients aged 65 to 80 after successful TAVI.
- Subclinical leaflet thrombosis occurred in 16.2% receiving anticoagulation versus 28.6% receiving aspirin.
- The combined safety outcome of bleeding, thromboembolic events and death occurred in 7.5% versus 10.6%, meeting the trial’s criterion for noninferiority.
- Earlier trials including GALILEO and ATLANTIS also found evidence that anticoagulation can reduce valve thrombosis, but did not establish a clear overall clinical benefit.
- ACASA-TAVI differs because it directly compared anticoagulant monotherapy with aspirin monotherapy.
- The new study does not prove that routine anticoagulation after TAVI prevents stroke, prolongs valve life or reduces mortality.
What Did the ACASA-TAVI Trial Test?
TAVI allows doctors to replace a diseased aortic valve using a catheter rather than conventional open-heart surgery. As the procedure has expanded to younger and healthier patients, the long-term durability of replacement valves has become increasingly important.
One concern is hypoattenuated leaflet thickening, or HALT. This CT finding is considered a form of subclinical leaflet thrombosis. Patients may have no symptoms, but imaging shows thickening of one or more valve leaflets consistent with a thrombotic process.
In the ACASA-TAVI randomized clinical trial, Dodgson et al. (2026) tested whether anticoagulation could reduce this problem without compromising safety compared with antiplatelet treatment.
Read the ACASA-TAVI trial in JAMA
Researchers enrolled 360 adults at three Norwegian centers. Participants were randomly assigned to receive 12 months of either a factor Xa inhibitor non-vitamin K antagonist oral anticoagulant, or NOAC, or aspirin.
The study was open-label, meaning patients and treating clinicians knew which treatment was being given. However, CT scans were evaluated by a blinded core laboratory and clinical endpoints were independently adjudicated.
Anticoagulation Reduced Leaflet Thrombosis
At 12 months, HALT was detected in 27 of 167 patients, or 16.2%, in the anticoagulation group compared with 48 of 168, or 28.6%, in the aspirin group.
The risk ratio was 0.55, with a 95% confidence interval of 0.37 to 0.82. The difference was statistically significant.
That translates to approximately a 45% relative reduction and a roughly 12 percentage-point absolute difference in CT-detected leaflet thrombosis.
The distinction between an imaging finding and a clinical event is crucial.
The trial did not show that anticoagulation reduced heart attacks or strokes by 45%. It showed that anticoagulation reduced an imaging marker of thrombus formation on the replacement valve.
Whether preventing HALT ultimately leads to fewer strokes, longer-lasting valves or improved survival remains uncertain.
What About Bleeding and Other Safety Outcomes?
Anticoagulants can increase bleeding, making safety particularly important when considering treatment for patients who do not otherwise require anticoagulation.
The study’s co-primary safety endpoint combined bleeding, thromboembolic events and death.
This occurred in 7.5% of patients assigned to anticoagulation and 10.6% assigned to aspirin. Anticoagulation met the study’s predefined criterion for noninferiority.
That should not be interpreted as proof that anticoagulation is safer than aspirin.
The overall number of safety events was relatively small, and the authors noted limitations surrounding the noninferiority margin because the observed event rate was lower than anticipated.
There was also an intriguing difference in mortality. Two patients assigned to anticoagulation died compared with 10 assigned to aspirin. However, the trial was not designed or large enough to establish a mortality benefit, so this finding should be considered exploratory rather than evidence that anticoagulation prolongs survival.
Earlier TAVI Trials Tell a More Complicated Story
ACASA-TAVI is not the first study to show that anticoagulation can reduce thrombotic changes on replacement valves.
In the GALILEO-4D substudy, De Backer et al. (2020) examined whether a rivaroxaban-based anticoagulation strategy affected valve leaflet abnormalities detected by four-dimensional CT after TAVI.
The study found that anticoagulation reduced CT-detected leaflet abnormalities compared with an antiplatelet-based strategy. Thickening of at least one valve leaflet occurred in 12.4% of patients receiving rivaroxaban compared with 32.4% receiving antiplatelet therapy. Reduced leaflet motion was also less common with the rivaroxaban-based strategy.
However, the larger GALILEO randomized trial by Dangas et al. (2020) produced a very different clinical result.
GALILEO was stopped early after the rivaroxaban-based strategy was associated with a higher risk of death or thromboembolic events and a higher risk of bleeding than the antiplatelet strategy.
The contrast between GALILEO and its imaging substudy demonstrated an important principle: a treatment can improve an imaging marker without improving overall outcomes for patients.
The ATLANTIS trial by Collet et al. (2022) added another layer to the evidence. The trial compared apixaban with standard care after TAVI and found that apixaban was not superior for the primary composite clinical outcome.
Among patients without another indication for anticoagulation, apixaban reduced obstructive valve thrombosis compared with antiplatelet therapy, but this did not translate into a clear overall clinical benefit.
These earlier trials provide important context for ACASA-TAVI. They suggest that anticoagulation can reduce thrombotic abnormalities on replacement valve leaflets, but reducing valve thrombosis on imaging does not by itself establish that patients will experience fewer strokes, live longer or have better overall outcomes.
What Is Different About ACASA-TAVI?
The new trial addressed a somewhat different question.
Previous TAVI anticoagulation trials evaluated various treatment regimens, including strategies involving combinations of anticoagulant and antiplatelet drugs.
ACASA-TAVI instead directly compared NOAC monotherapy with aspirin monotherapy in patients without an established indication for anticoagulation. In the NOAC group, 51% received apixaban, 41% edoxaban and 8% rivaroxaban.
This cleaner comparison is one reason the trial is important.
The findings again show that anticoagulation can substantially reduce leaflet thrombosis, but this time the benefit was achieved without an observed increase in the trial’s combined safety endpoint over 12 months.
That distinguishes ACASA-TAVI from GALILEO.
However, it does not establish that the ACASA-TAVI strategy is superior to those tested previously. The trials differed in medications, treatment combinations, patient populations, endpoints and design, and they were not head-to-head comparisons.
What Do the Trials Tell Us When Viewed Together?
Taken together, ACASA-TAVI, GALILEO and ATLANTIS reveal a consistent but unresolved question.
Anticoagulation appears capable of reducing thrombotic abnormalities on TAVI valve leaflets. What remains uncertain is whether preventing those abnormalities improves long-term patient outcomes enough to justify routine anticoagulation.
ACASA-TAVI moves the evidence forward because its anticoagulant-only strategy reduced HALT while meeting the study’s safety noninferiority criterion.
But its primary efficacy outcome remained an imaging finding.
The study included only 360 participants and followed them for 12 months. That is sufficient to demonstrate a meaningful difference in HALT, but not to establish whether treatment prevents relatively uncommon outcomes such as stroke, valve failure or death.
Does This Mean Everyone Should Take a Blood Thinner After TAVI?
No.
The trial involved patients aged 65 to 80, with a mean age of 74.5 years. The results may not apply to substantially older patients, particularly those with greater bleeding risk.
Treatment decisions after TAVI also depend on other medical conditions, bleeding risk and whether the patient already has an indication for anticoagulation, such as atrial fibrillation.
The longer-term consequences of HALT also remain an important unanswered question. If preventing leaflet thrombosis ultimately extends valve durability or reduces stroke, the clinical importance of ACASA-TAVI would increase substantially. If it does not, reducing an imaging abnormality alone may not justify exposing large numbers of patients to long-term anticoagulation.
What Does the Evidence Actually Tell Us?
ACASA-TAVI provides randomized evidence that NOAC monotherapy reduces CT-detected subclinical leaflet thrombosis compared with aspirin after TAVI in selected patients aged 65 to 80. It also met the trial’s predefined noninferiority criterion for the combined safety outcome of bleeding, thromboembolic events and death.
The result is encouraging, but the history of TAVI anticoagulation argues for caution.
GALILEO demonstrated that reducing valve thrombosis on imaging does not guarantee better clinical outcomes, while ATLANTIS also failed to establish an overall clinical advantage from routine anticoagulation.
ACASA-TAVI may have identified a more promising approach by comparing anticoagulation alone with aspirin alone. Whether that strategy ultimately produces fewer strokes, longer-lasting replacement valves or improved survival will require larger studies and longer follow-up.
For now, the most important finding is not simply that a blood thinner produced better CT scans. It is that a simpler anticoagulation strategy reduced leaflet thrombosis without an obvious safety penalty over 12 months, reopening a clinical question that earlier trials had left unresolved.
References
Dodgson, C. S., Herstad, J., Kløve, S. F., et al. (2026). Anticoagulation monotherapy vs antiplatelet monotherapy after transcatheter aortic valve implant: The ACASA-TAVI randomized clinical trial. JAMA. Advance online publication. https://doi.org/10.1001/jama.2026.17036
De Backer, O., Dangas, G. D., Jilaihawi, H., et al. (2020). Reduced leaflet motion after transcatheter aortic-valve replacement. New England Journal of Medicine, 382(2), 130–139. https://doi.org/10.1056/NEJMoa1911426
Dangas, G. D., Tijssen, J. G. P., Wöhrle, J., et al. (2020). A controlled trial of reivaroxaban after transcatheter aortic-valve replacement. New England Journal of Medicine, 382(2), 120–129. https://doi.org/10.1056/NEJMoa1911425
Collet, J. P., Van Belle, E., Thiele, H., et al. (2022). Apixaban vs standard of care after transcatheter aortic valve implantation: The ATLANTIS trial. European Heart Journal, 43(29), 2783–2797. https://doi.org/10.1093/eurheartj/ehac242
