PROGRESS Trial: TAVR Improves Outcomes for Patients with Moderate Aortic Stenosis and At-Risk Features
SAN DIEGO – In a randomized trial of patients with moderate aortic stenosis (AS) and at least one at-risk feature, those who underwent earlier transcatheter aortic valve replacement (TAVR) had improved outcomes at two years than those managed with clinical surveillance (CS). In addition to being safe and effective, TAVR reduced heart failure events and hospitalizations and prevented a meaningful decline in quality of life in this patient population.
Findings were reported today at TCT® 2026, the annual scientific symposium of the Cardiovascular Research Foundation® (CRF®). TCT is the world’s premier educational meeting specializing in interventional cardiovascular medicine.
Current guidelines recommend monitoring patients with moderate AS, both clinically and with echocardiography every one to two years. However, the severity and impact of moderate AS can vary widely, and progression to severe AS can occur rapidly. Observational studies suggest that some patients with moderate AS and at-risk features may face outcomes similar to those of patients with severe AS.
PROGRESS was a prospective, multicenter, randomized, controlled trial which compared transfemoral TAVR using a balloon-expandable valve with guideline-recommended clinical surveillance in patients with moderate AS and at least one of the following at-risk features: valve-related symptoms (NYHA Class ≥ II); left ventricular ejection fraction (LVEF) < 60%; diastolic dysfunction grade ≥ 2; stroke volume index < 35 mL/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).
Between October 2021 and January 2024, a total of 744 patients were randomized 1:1 to undergo TAVR (n=373) or CS (n=371) at 74 centers across the U.S., Japan, Australia, Europe and Canada. At baseline, the mean age was 78.4 years, 60.9% were male, and the mean Society of Thoracic Surgeons score was 3.0%, 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 (72.0%) had at least two or more at-risk features, and 40% had three or more.
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), hospitalization 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 TAVR population (n=358, Upper 97.5% CL: 8.8% vs 13.7% performance goal, p < 0.001). The primary effectiveness endpoint, the composite of death or a heart failure (HF) event at two years, occurred significantly more often in the CS group than in the TAVR group [23.9% vs. 16.7%, HR (95%CI): 0.67 (0.48, 0.93), Δ –7.2 (–13.1, –1.3), p=0.02]. Heart failure events were also more frequent in the CS group than in the TAVR group [19.0% vs. 10.8%, HR (95%CI): 0.55 (0.37, 0.81), p = 0.002]. In addition, HF hospitalizations were more frequent in the CS group [14.9% vs. 7.4%, HR (95%CI): 0.48 (0.30, 0.77), p=0.001]. The benefit of TAVR for the primary effectiveness endpoint was consistent across all subgroups.
The prespecified hierarchical secondary endpoint of death, stroke, or heart failure hospitalization at two years occurred in 17.7% of TAVR patients and 23.3% of CS patients [ 95% CI: -5.6 (–11.5, 0.3), p=0.07]. Survival with an improvement of at least 10 points in KCCQ overall summary score at one and two years was higher among TAVR patients [39.0% versus 23.2%, 95% CI: 15.7 (8.8, 22.6), p < 0.001]. During the two-year follow-up, 204 patients initially randomized to CS underwent delayed 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.
“The clinical significance of moderate aortic stenosis should not be underestimated, and these patients should be referred promptly to a valve clinic for comprehensive evaluation to establish the optimal management strategy,” said Philippe Genereux, MD, director of the Structural Heart Program at Atlantic Health Morristown Medical Center. “The PROGRESS trial shows that patients with moderate aortic stenosis and at-risk features can safely benefit from earlier TAVR and should not wait for disease progression, ultimately achieving a better quality of life and avoiding decline in their health status.”
The study was funded by Edwards Lifesciences.
Dr. Genereux disclosed consulting fees from Abbott Vascular, Cardiawave, Egnite, EchoIQ, Edwards Lifesciences, Haemonetics, Medtronic, Pi-Cardia, Puzzle Medical Inc., Spiralis Medical, 4C Medical, Shockwave Medical and Antegrade Medical as well as equity with Puzzle Medical Inc., Pi-Cardia, Antegrade Medical, Spiralis Medical, Echo IQ, Cardiawave and Sparrow Bioacoustics.
The results of the study were presented on Monday, November 2 at 9:40 AM PT in the Main Arena at the San Diego Convention Center during TCT 2026 and simultaneously published in The New England Journal of Medicine.
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