NOTION 3 Results Bolster the Notion of Pre-TAVI Coronary Intervention

The NOTION 3 trial, presented at ESC 2024 and published in The New England Journal of Medicine, contributes important data to the ongoing debate about the role of percutaneous coronary intervention (PCI) before transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and significant coronary artery disease (CAD). While the topline study results generally favor PCI before TAVI, the answer to this question for a given patient probably remains the same: “It depends.”

Managing CAD in patients undergoing TAVI has always been complex. CAD is common among these patients, with approximately 50% presenting with significant coronary lesions. Historically, the approach to revascularization in the context of TAVI has been varied, largely due to the lack of clear evidence supporting either strategy. Prior studies, such as the ACTIVATION trial, failed to show a significant benefit of PCI before TAVI, leading to a continued reliance on clinical judgment and individualized patient care.

The NOTION 3 trial sought to provide clarity by randomizing 455 patients (median age of 82 years, 33% women, median SYNTAX score of 9, median STS-predicted 30-day mortality risk of 3%) with severe symptomatic aortic stenosis and significant CAD—defined by a fractional flow reserve (FFR) of ≤0.80 or a diameter stenosis of ≥90%—to either PCI followed by TAVI (N = 227) or TAVI alone (N = 228). The study’s primary endpoint was the incidence of major adverse cardiac events (MACE), a composite of death from any cause, myocardial infarction, or urgent revascularization, over a median follow-up period of two years. Balloon-expandable valves were used in 41.5% of patients. Those with left main coronary stenosis were excluded.

The results showed a significant reduction in MACE in the PCI group compared to the conservative treatment group (26% vs. 36%, hazard ratio 0.71, 95% CI 0.51 to 0.99; p=0.04), despite a greater number of significant coronary lesions in the PCI group. Importantly, this seems to have been driven by each of the individual endpoints. However, the clinical significance of this finding should be interpreted cautiously. The Kaplan-Meier curves for MACE were largely superimposed during the first year, indicating that the benefits of PCI became apparent only later in the follow-up period. Additionally, PCI was associated with a higher risk of bleeding, with 28% of patients in the PCI group experiencing bleeding events compared to 20% in the conservative treatment group (hazard ratio 1.51, 95% CI 1.03 to 2.22).

These findings suggest that while PCI may reduce the risk of adverse events in the long term, the immediate benefits are less clear, and the increased risk of bleeding must be carefully weighed. For heart teams, this data underscores the importance of individualized decision-making. Rather than establishing a new standard of care, the NOTION 3 trial highlights the need for a nuanced approach where the decision to perform PCI is tailored to each patient’s specific clinical scenario.

In practice, these results may not change the management of all patients undergoing TAVI but can help facilitate more informed discussions with patients. The similar outcomes observed in the first year between the PCI and conservative groups provide an opportunity to involve patients in shared decision-making, particularly when considering the risks of additional interventions like PCI.

Ultimately, the NOTION 3 trial enriches the body of evidence, favoring the decision to perform PCI for significant coronary lesions pre-TAVI in select patients. Clinical judgment, patient preferences, and individualized risk assessment remain central to optimal patient care.

References

Lønborg J, Jabbari R, Sabbah M, et al. Percutaneous Coronary Intervention in Patients Undergoing Transcatheter Aortic-Valve Implantation. N Engl J Med. 2024; DOI:10.1056/NEJMoa2401513.