NOTION-3 Investigates CAD Management in TAVR Patients

September 13, 2024—The European Society of Cardiology (ESC) recently announced findings from the open-label, investigator-initiated NOTION-3 trial showing that percutaneous coronary intervention (PCI) significantly improved outcomes in patients with stable coronary artery disease (CAD) and severe aortic stenosis selected for transcatheter aortic valve implantation/replacement (TAVI/TAVR).

The Principal Investigator of NOTION-3 is Jacob Thomsen Lønborg, MD, from the Copenhagen University Hospital in Copenhagen, Denmark.

The NOTION-3 results were presented as late-breaking research in a Hot Line session at the ESC Congress 2024 held August 30 to September 2 in London, United Kingdom. The NOTION-3 trial was simultaneously published by Dr. Lønborg et al in The New England Journal of Medicine.

According to ESC, eligible participants in the NOTION-3 trial had been selected for TAVR because they had severe aortic valve stenosis and at least one physiologically significant PCI-eligible coronary artery stenosis (fractional flow reserve ≤ 0.80 or diameter stenosis > 90% in a coronary artery ≥ 2.5 mm in diameter).

As summarized in the ESC press release, patients were randomized in a 1:1 ratio to either complete revascularization with PCI in addition to TAVR or conservative management with TAVR alone. The primary endpoint was the composite of all-cause mortality, myocardial infarction (MI), or urgent revascularization until the last included patient was followed for 1 year after TAVR.

The study enrolled 455 patients at 12 centers in Denmark, Finland, Latvia, and Sweden. The mean age was approximately 81 years, and 33% were female. The mean Society of Thoracic Surgeons risk score was 3%. Approximately 60% of patients had angina symptoms (Canadian Cardiovascular Society grade ≥ 1). PCI was performed before TAVR in 74% of patients, concomitantly with TAVR in 17%, and shortly after in 9%.

As reported in the ESC press release, the findings included the following:

• Incidence of the primary composite endpoint was significantly lower in the PCI group compared with the conservative group (26% vs 36%; hazard ratio [HR], 0.71; 95% CI, 0.51-0.99; P = .041) after a median follow-up of 2 years.
• Significantly lower rates were observed with PCI compared with conservative treatment for MI (8% vs 14%; HR, 0.54; 95% CI, 0.30-0.97; P = .037) and for urgent revascularization (2% vs 11%; HR, 0.20; 95% CI, 0.08-0.51; P < .001).
• Similar rates were observed in the PCI group and the conservative group for all-cause mortality (23% and 27%; HR, 0.85; 95% CI, 0.59-1.23; P = .4).
• The rate of bleeding events—minor, major, life-threatening, or disabling—was 28% in the PCI group and 20% in the conservative group (HR, 1.51; 95% CI, 1.03-2.22).

“TAVI is being increasingly used to treat patients with severe aortic valve stenosis,” commented Dr. Lønborg in the ESC press release. “Many of these patients also have CAD, but whether patients should undergo PCI to treat CAD in addition to TAVI is uncertain due to their older age and risk of complications.”

He continued, “We designed the NOTION-3 trial to investigate the efficacy and safety of PCI in addition to TAVI compared with conservative management using TAVI alone and found that PCI plus TAVI is in fact beneficial.”

Dr. Lønborg concluded, “NOTION-3 has answered an important clinical question, demonstrating that TAVI patients with CAD can derive considerable benefits from PCI, driven by reductions in MI and urgent revascularization. We suggest that performing PCI should be the recommended treatment for patients undergoing TAVI [who] have CAD, but the final decision should be made based on the patient’s age, comorbidities, life expectancy, and bleeding risk.”