Patients with moderate aortic stenosis (AS) undergoing transcatheter aortic valve intervention (TAVI) had improved outcomes at two years than those left under clinical surveillance, results of the PROGRESS trial, presented during a late-breaking trials session at the Transcatheter Cardiovascular Therapeutics (TCT) conference (31 October–3 November, San Diego, USA), have shown.
PROGRESS, a prospective, multicentre, randomised, controlled trial, compared transfemoral TAVI using the Sapien 3 (Edwards Lifesciences) valve with guideline-recommended clinical surveillance in patients with moderate AS and at least one at-risk feature.
Presenting the results at TCT 2026, Philippe Généreux (Morristown Medical Center, Morristown, USA) reported that the result was mainly driven by a reduction in hospitalisations for heart failure in patients who underwent TAVI, which were reduced by 52% at two years compared to patients who did not undergo the treatment.
A total of 744 patients were enrolled in the trial at 74 centres between October 2021 and January 2024 and randomised 1:1 to undergo TAVI (n=373) or remain under clinical surveillance (n=371).
At baseline, the mean age was 78.4 years, 60.9% were male, and the mean Society of Thoracic Surgeons (STS) score was 3%, with 45.6% of patients deemed low risk by the site heart team. More than one third of patients (35.5%) had severe symptoms (NYHA class III or IV), and the mean baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) score was 64.2.
Most patients (72%) had at least two or more at-risk features—which included valve-related symptoms; left ventricular ejection fraction (LVEF) < 60%; diastolic dysfunction grade ≥ 2; stroke volume index <35mL/m²; atrial fibrillation within the last six months; NT-Pro BNP >3x the upper limit of normal; or an elevated aortic valve calcium score on computed tomography (CT). Forty per-cent of patients had three or more of these risk factors.
The primary safety endpoint of the trial was met, defined as the composite of death, stroke, life threatening or fatal bleeding, stage four acute kidney injury (AKI), hospitalisation due to a device- or procedure-related complication, or valve dysfunction requiring reintervention at 30 days. This occurred in 5.9% of the as-treated TAVI population.
The primary effectiveness endpoint, the composite of death or a heart failure event at two years, occurred significantly more often in the clinical surveillance group than in the TAVI group (23.9% vs. 16.7%). Heart failure events were more frequent in the clinical surveillance group than in the TAVI group (19% vs. 10.8%). Heart failure hospitalisations were more frequent in the clinical surveillance group (14.9% vs. 7.4%). The benefit of TAVI for the primary effectiveness endpoint was consistent across all subgroups.
The prespecified hierarchical secondary endpoint of death, stroke, or heart failure hospitalisation at two years occurred in 17.7% of TAVI patients and 23.3% of clinical surveillance patients. Survival with an improvement of at least 10 points in KCCQ overall summary score at one and two years was higher among TAVI patients (39% vs. 23.2%).
During the two-year follow-up, 204 patients initially randomised to clinical surveillance underwent delayed aortic valve replacement (AVR). Approximately 80% had progressed to severe AS by the time of the delayed AVR procedure. These patients also experienced a significant decline in KCCQ scores before AVR, followed by significant improvement by 30 days after the procedure, Généreux reported.
Généreux said that the study should prompt physicians to consider following patients with moderate AS more closely, due to the potentially rapid progression of the disease.
“I think the most important learning from progress is AS is not benign; this disease progressed faster than we expected,” Généreux commented. “The low-hanging fruit for me is to bring those patients in clinic to have a comprehensive assessment and to follow them if you don’t want to treat them, maybe [for] six months, 12 months, [but] not one to two years.
“That’s going to create a little bit of a turning point in the way we see patients with aortic stenosis. I think we’ve been very complacent, waiting until it’s severe. We don’t want to go too early, obviously, but I think there’s a sweet spot, and I think the PROGRESS trial identifies the optimal timing of intervention based on safety and efficacy.”
Patients in the trial will be followed out to 10 years. Results of the study were simultaneously published in the New England Journal of Medicine.
