Background Frailty is an important predictor of outcomes in patients with coronary artery disease (CAD) and following transcatheter aortic valve implantation (TAVI). The NOTION-3 trial demonstrated that performing percutaneous coronary intervention (PCI) in addition to TAVI reduced the risk of major adverse cardiac events (MACE). Whether this benefit applies to frail patients remains uncertain.
Objective This study aims to evaluate efficacy and safety of PCI in frail TAVI patients with CAD.
Methods NOTION-3 was an international, open-label, randomized superiority trial enrolling patients with CAD and severe aortic stenosis undergoing TAVI. Patients were randomized 1:1 to PCI or conservative treatment. Frailty was assessed post-hoc by a calculated frailty score derived from baseline data on symptom-related limitations, daily function, and quality of life. Primary endpoint was a composite of all-cause mortality, myocardial infarction (MI), and urgent coronary revascularization. Safety endpoints included bleeding and acute kidney injury.
Results Frailty data were available for 407 (90%) patients, of whom 130 patients (32%) were frail. During median follow-up of 2[IQR 1-4] years, PCI reduced MACE in non-frail patients (15% vs. 33%; HR0.42, 95%CI 0.25-0.69, p<0.001), as well as death from any cause (p=0.019), MI (p=0.004) and urgent revascularization (p=0.005). No differences were observed in frail patients. In contrast, frail patients undergoing PCI had more bleeding events (HR2.51, 95%CI 1.23-5.11, p=0.011).
Conclusion In non-frail patients with CAD undergoing TAVI, PCI lowered the risk of MACE, all-cause mortality and MI, as compared to conservative treatment. In frail patients PCI increased bleeding without clinical benefit. Our findings require confirmation in larger prospective studies.
Editors
Editor-in-Chief
Harlan M. Krumholz, MD, SM, FACC
CME Editor
Ragavendra R. Baliga, MD
Author
Hanna Ratcovich, MD, PhD
Important Dates
Date of Release: April 13, 2026
Term of Approval/Date of CME/MOC Expiration: April 12, 2027