By Jeffrey Zimmet, MD, PhD
In this randomized trial of patients undergoing transcatheter aortic valve replacement (TAVR), with an average of one severe coronary stenosis, percutaneous coronary intervention in addition to TAVR reduced the incidence of the combined endpoint of all-cause mortality, myocardial infarction, and urgent revascularization at two years.
Lønborg J, Jabbari R, Sabbah M, et al. PCI in patients undergoing transcatheter aortic-valve implantation. N Engl J Med. 2024; Aug 31. doi: 10.1056/NEJMoa2401513. [Online ahead of print].
Approximately half of all patients undergoing evaluation for transcatheter aortic valve replacement (TAVR) have concomitant coronary artery disease, and yet there is no standard approach when it comes to decision-making about percutaneous revascularization.
In the early days of TAVR, percutaneous coronary intervention (PCI) of significant lesions prior to the valve procedure was exceedingly common. In more recent years, some TAVR operators and centers have taken a more pragmatic and individualized approach, with some recommending PCI only for patients with angina, and some programs foregoing coronary evaluation altogether. To date, there has been little available data to guide PCI decision-making in these patients.
The previously presented ACTIVATION trial was relatively underpowered and was terminated early at one year for futility. The current NOTION-3 trial was designed to fill this knowledge gap. The trial was funded by the Danish Heart Foundation and by Boston Scientific, although Boston Scientific was not involved in the conduct of the trial or the preparation of the manuscript.
Between September 2017 and October 2022, 455 patients planned for TAVR, with at least one severe coronary lesion, were enrolled at 12 hospitals in the Nordic-Baltic region. Coronary stenoses were eligible if they were significant by fractional flow reserve testing. Critically severe stenoses (90% or greater) did not require physiologic testing to qualify.
There were 455 patients with a median age of 82 years, 32% female, who were randomized 1:1 to PCI or conservative therapy. Most had a single qualifying coronary lesion. In the PCI group, 74% of patients had PCI prior to the TAVR procedure, with the remainder being done during or soon after TAVR. Eighty-nine percent of the PCI group achieved complete revascularization, although eight patients did not receive PCI.
At two-year follow-up, a major adverse cardiac event — a composite of all-cause death, myocardial infarction (MI), or urgent revascularization — had occurred in 60 patients (26%) in the PCI group, compared with 81 (36%) in the medical therapy group (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.51-0.99; P = 0.04).
Among the components of the primary endpoint, mortality was not significantly different between groups, but both MI (7% vs. 14%) and urgent revascularization (2% vs. 11%) were lower in the PCI group. The incidence of any significant bleeding was higher in the PCI group (28% vs. 20%; HR, 1.51; 95% CI, 1.03-2.22), while major bleeding was not different. Only seven patients (3%) had any reported complications of the PCI procedure.
The authors concluded that, among patients with significant coronary artery disease undergoing TAVR, PCI was associated with a lower risk of major adverse events compared with conservative treatment. They suggested that PCI should be considered in all patients with similarly severe coronary disease undergoing TAVR.
Commentary
NOTION-3 is undoubtedly an important trial that will affect clinical decision-making for a large proportion of TAVR patients going forward. And yet I admit I am not certain how to fully explain these results.
Obstructive coronary disease often is found in patients being evaluated for TAVR and most often is an incidental finding. We should understand that in most patients such as these — mostly single-vessel disease with low coronary lesion complexity scores — PCI is not necessary to improve the safety of the TAVR procedure itself. If urgent revascularization was the main driver of the primary endpoint here, that would be understood easily, since the knowledge that a patient has a severe un-revascularized coronary lesion may very well lead to this outcome.
However, explaining the reported reduction in MI is more obscure and, ultimately, may be the major driver of how we view these results. Trials of PCI in stable atherosclerotic coronary disease have, for the most part, failed to demonstrate advantages in terms of hard events, such as acute coronary syndrome. These authors theorized that TAVR may lead to changes in coronary vessel wall shear stress, thus making plaque more unstable or vulnerable. It also is plausible that patients who increase their physical activity after TAVR may subsequently unmask symptoms of coronary ischemia.
NOTION-3 suggests that revascularization should at least be considered for patients undergoing TAVR evaluation who are found to have severe coronary disease that is amenable to PCI, irrespective of whether they have angina. Review of the NOTION-3 supplementary material shows that more than two-thirds of enrolled patients were Canadian Cardiovascular Society (CCS) angina class 0 or 1 at baseline, with most of the remainder being CCS 2. Even in the conservative management group, 82% of patients were class 0 (no angina) at one month post-TAVR. Of course, each patient’s clinical status and anatomy should guide individual management, but these results provide food for thought and are likely to drive further use of PCI in the TAVR population. We will await the eventual results of the similar COMPLETE TAVR trial, which intends to enroll 4,000 patients and has an estimated completion date in 2026.
Jeffrey Zimmet is Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center.
