Four late-breaking trials presented at ESC Congress 2026 offer new insights into the management of structural heart disease and heart failure (HF). TAVI PCI investigated which treatment strategy is preferred when both TAVI and PCI are planned, ACASA-TAVI and NOTION-4 compared antithrombotic therapy strategies post-TAVI, and TRIC-I-HF examined strategies for tricuspid intervention in HF.

TAVI PCI: TAVI First or PCI First?

Coronary artery disease (CAD) frequently coexists with severe aortic stenosis (AS), creating a key dilemma: Should the valve or coronary disease be treated first? PCI before TAVI has commonly been performed, but in older patients with severe AS, PCI may add contrast exposure, bleeding risk, myocardial injury, and antiplatelet burden.

The TAVI PCI trial directly addressed procedural sequencing.1 This international, open-label, randomized, noninferiority trial enrolled 986 patients with severe AS and concomitant CAD who were candidates for both procedures. Patients were randomized to a TAVI-first or PCI-first strategy, with the second procedure performed within 45 days.

At one year, the primary composite of death; nonfatal myocardial infarction (MI); ischemia-driven revascularization; valve-, procedure-, or HF-related hospitalization; and life-threatening, disabling, or major bleeding occurred in 22.2% with TAVI first vs. 24.2% with PCI first (risk difference, −2.0 percentage points; 95% CI, −7.4 to 3.4; p<0.001 for noninferiority). Serious adverse events were similar between groups.

Putting TAVI PCI in Context

TAVI PCI complements PRO-TAVI, in which deferral of PCI was noninferior to PCI before TAVI for a one-year composite of death, MI, stroke, and major bleeding (24% vs. 26%).2 Together, these trials challenge routine PCI before TAVI in appropriately selected patients. However, NOTION-3 showed that PCI benefits selected patients with significant CAD, reducing death, MI, or urgent revascularization, although more bleeding occurred.3 Thus, the emerging evidence separates two questions: Who needs PCI, and when should it be performed?

Clinical Perspective

TAVI first may be particularly attractive in patients with stable CAD, high bleeding risk, or lesions of uncertain clinical significance. PCI-first may reasonably be considered for patients with an acute coronary syndrome, critical coronary anatomy, or lesions in which prompt revascularization is clinically important. The sequence should also consider lesion complexity, ischemic significance, bleeding risk, coronary access after TAVI, and the likelihood that CAD will remain clinically important after valve replacement.

Bottom Line

The TAVI PCI trial establishes TAVI first as a legitimate alternative to PCI first, rather than a universal replacement. Contemporary management should emphasize individualized Heart Team decision-making based on coronary anatomy, ischemic significance, bleeding risk, procedural complexity, and anticipated coronary access.

ACASA-TAVI: Should Anticoagulation Replace Aspirin After TAVI?

Subclinical leaflet thrombosis, manifested as hypoattenuated leaflet thickening (HALT) on four-dimensional CT, is common after TAVI. Whether preventing HALT with routine anticoagulation improves clinical outcomes, however, remains uncertain.

The ACASA-TAVI trial randomized 360 patients aged 65-80 years without another indication for oral anticoagulation (OAC) to 12 months of non–vitamin K antagonist oral anticoagulant (NOAC) monotherapy or aspirin 75 mg daily. HALT occurred in 16.2% in the NOAC group vs. 28.6% in the aspirin group (risk ratio, 0.55; 95% CI, 0.37-0.82; p=0.004). The prespecified safety composite of Valve Academic Research Consortium-3 bleeding, thromboembolic events, and death occurred in 7.5% vs. 10.6%, respectively, meeting the criterion for noninferiority.4

Clinical Perspective

ACASA-TAVI demonstrates that 12 months of NOAC monotherapy reduces CT-detected HALT compared with aspirin and was noninferior for the prespecified safety composite. However, HALT remains a surrogate imaging endpoint, and the trial was not powered to establish clinical benefit or improved valve durability.

These findings should be considered alongside the NOTION-4 trial (see below). Importantly, the 2025 ESC/EACTS guidelines recommend low-dose aspirin (75-100 mg/day) for 12 months after TAVI in patients without an indication for OAC, followed by consideration of long-term aspirin, and state that routine OAC is not recommended in patients without a baseline indication.5 Thus, ACASA-TAVI should not yet be interpreted as a mandate to replace aspirin with anticoagulation. Rather, it provides evidence that sustained anticoagulation can reduce subclinical leaflet thrombosis and supports further investigation into whether this imaging benefit translates into improved valve durability or clinical outcomes.

Bottom Line

ACASA-TAVI shows that 12 months of NOAC monotherapy reduced CT-detected HALT by approximately 45% vs. aspirin and was noninferior for the prespecified 12-month safety composite. Whether this imaging benefit translates into better valve durability or clinical outcomes remains unanswered.

NOTION-4: Can Short-Term Anticoagulation Reduce Leaflet Thrombosis After TAVI?

The NOTION-4 trial tested whether three months of DOAC therapy after TAVI could provide sustained protection against HALT after treatment discontinuation.6

The trial randomized 352 patients without an indication for OAC after successful TAVI to lifelong SAPT or three months of DOAC therapy followed by lifelong SAPT. At three months, HALT was lower with patients taking DOACs (12.1% vs. 31.8%), but this benefit was not sustained after treatment discontinuation. Over 12 months, HALT occurred in 28.3% vs. 32.2%, respectively (risk difference, −3.9 percentage points; 95% CI, −14.4 to 6.6; p=0.54).

A concerning clinical outcome signal also emerged. At 12 months, the composite of all-cause death, stroke, or major/life-threatening bleeding occurred in 8.2% with DOAC therapy vs. 2.3% with SAPT therapy (risk difference, 5.9 percentage points; 95% CI, 1.2-10.6). Although the trial was not powered for clinical events, there was no demonstrated clinical benefit from suppressing early HALT.

Clinical Perspective

NOTION-4 highlights the critical distinction between biological efficacy and clinical benefit. DOAC therapy suppresses HALT during treatment, but recurrence after discontinuation suggests that short-term anticoagulation does not provide durable suppression of leaflet thrombosis. These findings align with the broader evidence. The GALILEO trial showed that a rivaroxaban-based strategy reduced subclinical leaflet-motion abnormalities and leaflet thickening but increased the risk of death or thromboembolic events and major bleeding.7

Bottom Line

NOTION-4 demonstrates that three months of DOAC therapy substantially reduces early HALT, but this effect is largely attenuated after treatment cessation and is not accompanied by demonstrated clinical benefit. HALT should not be treated in isolation until preventing it is shown to improve stroke, valve durability, reintervention, or survival.

TRIC-I-HF: Can Tricuspid Intervention Change the Course of HF?

Severe tricuspid regurgitation (TR) is increasingly viewed not merely as a marker of advanced HF, but as a contributor to right-sided congestion, end-organ dysfunction, recurrent hospitalization, and impaired quality of life. Although transcatheter tricuspid valve intervention (TTVI) reduces TR and improves symptoms, its effect on hard clinical outcomes has remained uncertain.

The TRIC-I-HF trial included 360 patients with symptomatic severe TR and increased risk of future HF events, randomized 2:1 to TTVI plus medical therapy or medical therapy alone. Mean age was 80 years, and 56% were women. The one-year hierarchical endpoint of death, HF hospitalization, and quality-of-life improvement favored intervention (win ratio, 2.42; 95% CI, 1.76-3.33; p<0.001). At three years, freedom from death or HF hospitalization was 52.4% vs. 21.0%, corresponding to a 60% lower risk (hazard ratio, 0.40; 95% CI, 0.29-0.55; p<0.001). Tricuspid transcatheter edge-to-edge repair (T-TEER) accounted for 98% of interventions; 30-day major adverse events occurred in 5.9%.8

These findings extend earlier randomized evidence. The TRILUMINATE Pivotal trial reduced TR and improved health status, but T-TEER did not significantly reduce death or HF hospitalization at one year. At two years, T-TEER reduced recurrent HF hospitalizations without a demonstrated mortality benefit.9 The Tri.Fr trial similarly improved its hierarchical composite endpoint, driven primarily by improvements in health status rather than fewer clinical events.10

Clinical Perspective

TRIC-I-HF represents an important shift in the field—from asking “Can we make patients feel better?” to asking “Can treating TR alter the trajectory of HF?” Its findings suggest that, in appropriately selected high-risk patients, transcatheter repair may improve health status and reduce the risk of death or HF hospitalization. Nevertheless, these results should not be generalized to all patients with severe TR. TRIC-I-HF was relatively small, open-label, used 2:1 randomization, and enrolled a selected high-risk population. The optimal timing of intervention, durability of benefit, and patient characteristics associated with prognostic benefit remain uncertain.

Bottom Line

TRIC-I-HF provides important, randomized evidence that TTVI may be more than symptomatic therapy, with potential effects on HF-related clinical outcomes in selected high-risk patients. These findings support earlier Heart Team evaluation before advanced right ventricular or end-organ dysfunction develops, while recognizing the need for confirmation in broader populations.

References

Stähli BE, Ruschitzka F, Westermann D, et al. Timing of PCI in patients undergoing transcatheter aortic-valve implantation. N Engl J Med. Published online August 30, 2026. doi:10.1056/NEJMoa2606924
Delewi R, Aarts HM, Broeze GM, et al. Deferral of percutaneous coronary intervention in patients undergoing transcatheter aortic valve implantation (PRO-TAVI): an investigator-initiated, multicentre, open-label, non-inferiority, randomised controlled trial. Lancet. 2026;407(10537):1429-1438. doi:10.1016/S0140-6736(26)00308-9
Lønborg J, Jabbari R, Sabbah M, et al. PCI in patients undergoing transcatheter aortic-valve implantation. N Engl J Med. 2024;391(23):2189-2200. doi:10.1056/NEJMoa2401513
Dodgson CS, Herstad J, Kløve SF, et al. Anticoagulation monotherapy vs antiplatelet monotherapy after transcatheter aortic valve implant: the ACASA-TAVI randomized clinical trial. JAMA. Published online August 30, 2026. doi:10.1001/jama.2026.17036
Praz F, Borger MA, Lanz J, et al. 2025 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J. 2025;46(44):4635-4736. doi:10.1093/eurheartj/ehaf194
Jørgensen TH, Larsen AF, Jensen JM, et al. Short-term anticoagulant therapy and subclinical leaflet thickening in transcatheter aortic valves: the NOTION-4 trial. J Am Coll Cardiol. Published online August 30, 2026. doi:10.1016/j.jacc.2026.08.023
De Backer O, Dangas GD, Jilaihawi H, et al. Reduced leaflet motion after transcatheter aortic-valve replacement. N Engl J Med. 2020;382:130-139. doi:10.1056/NEJMoa1911426
Hausleiter J, Stocker TJ, Geisler T, et al. Tricuspid-valve intervention in heart failure. N Engl J Med. Published online August 30, 2026. doi:10.1056/NEJMoa2606934
Kar S, Makkar RR, Whisenant BK, et al. Two-year outcomes of transcatheter edge-to-edge repair for severe tricuspid regurgitation: the TRILUMINATE Pivotal randomized controlled trial. Circulation. 2025;151(23):1630-1638. doi:10.1161/CIRCULATIONAHA.125.074536
Donal E, Dreyfus J, Leurent G, et al. Transcatheter edge-to-edge repair for severe isolated tricuspid regurgitation: the Tri.Fr randomized clinical trial. JAMA. 2025;333(2):124-132. doi:10.1001/jama.2024.21189


Keywords:
ESC Congress, ESC26, Transcatheter Aortic Valve Replacement, Aortic Valve Stenosis, Protamines, Antithrombotic Therapy, Platelet Aggregation Inhibitors, Anticoagulants, Thrombosis, Heart Valve Prosthesis