Stenting, TAVR Make Sense Packaged Together for Some Patients

LONDON — Some individuals already undergoing transcatheter aortic valve replacement (TAVR, also TAVI) might as well get coronary lesions revascularized around the same time, according to the NOTION-3 randomized trial.

Clinical benefit was shown when older people got both TAVR for their severe aortic stenosis (AS) and percutaneous coronary intervention (PCI) for their stable coronary artery disease (CAD), with combined major adverse cardiac events at 2 years reaching 26% in this group versus 36% for those assigned TAVR plus conservative treatment alone for any significant CAD (HR 0.71, 95% CI 0.51-0.99).

Two out of the three individual endpoint components supported the overall signal of benefit for add-on PCI, reported Jacob Lønborg, MD, PhD, of Copenhagen University Hospital-Rigshospitalet in Denmark:

• Myocardial infarction: 7% vs 14% (HR 0.54, 95% CI 0.30-0.97)
• All-cause death: 23% vs 27% (HR 0.85, 95% CI 0.59-1.23)
• Urgent revascularization: 2% vs 11% (HR 0.20, 95% CI 0.08-0.51)

As expected, the trade-off to the improvement in the primary composite outcome was an uptick in bleeding of any kind (28% vs 20%, HR 1.51, 95% CI 1.03-2.22), Lønborg said in a presentation at the European Society of Cardiology (ESC) meeting. Results were simultaneously published in the New England Journal of Medicine.

“For patients treated with TAVI who also have stable CAD, performing PCI should be the standard of care,” Lønborg concluded from NOTION-3. Nevertheless, he said, the final decision to perform PCI or not should be individualized, taking into account each patient’s age, life expectancy, and other factors.

Notably, on subgroup analysis, the patients presenting with at least one lesion with diameter stenosis ≥90% had disproportionately more benefit with add-on PCI in lieu of conservative therapy (24% vs 37%, HR 0.53, 95% CI 0.34-0.82), the authors found.

“Our trial does not provide any explanation for these findings, but it is possible that a change in coronary physiological characteristics after TAVI affects vessel-wall shear stress, thus making the plaque more unstable; that patients become more physically active after TAVI, thereby unmasking symptoms and events related to coronary artery disease; or that the events due to untreated coronary stenosis represent the natural history of coronary artery disease,” they wrote.

Lønborg’s group noted that there are currently no guideline recommendations regarding PCI in TAVR candidates, even though approximately half of TAVR patients also have CAD, and the combination of the two procedures is already practiced in 10-20% of cases in the real world.

ESC session discussant Shamir Mehta, MD, MSc, of McMaster University in Hamilton, Ontario, Canada, thus called the NOTION-3 a “very important trial addressing a very common question:” Who should have PCI coupled with TAVR and when?

NOTION-3 included 455 TAVR patients with at least one coronary AS eligible for PCI (due to fractional flow reserve ≤0.80 or diameter stenosis ≥90%). Excluded were people needing valve-in-valve TAVR and those with a life expectancy under 1 year, severe renal failure, left main CAD, or recent acute coronary syndrome.

Mehta emphasized that the study ultimately had a modest sample size in which 40-50% of people had asymptomatic CAD and the cohort mostly underwent relatively low-risk PCI.

He questioned if the study was large enough and the results robust enough to change guidelines. If most of the benefit comes down to fewer urgent revascularizations, “Why not tailor PCI for symptomatic patients after TAVR? That might save most elderly patients from unnecessary PCI, bleeding, and DAPT exposure,” he suggested.

Lønborg had reported that 74% of PCIs were staged before TAVR in NOTION-3; the effect of how the procedures are timed has yet to be studied.

As for antithrombotics, the PCI group generally got aspirin indefinitely after the procedure and also took clopidogrel (Plavix) for the first 6 months. However, those with an indication for oral anticoagulation had aspirin shortened to the first month only — amended mid-trial to just 7 days following the AUGUSTUS trial — while clopidogrel was kept to the first 6 months and the anticoagulation continued indefinitely.

“NOTION-3 is a huge advance, but we need additional evidence and larger [randomized clinical trials],” Mehta stressed.

One example is the ongoing COMPLETE TAVR trial with its estimated 4,000 participants, he said.

NOTION-3 was an open-label trial powered for superiority. It was conducted at 12 hospitals from 2017 to 2022 in the Nordic-Baltic countries.

Participants had a median age of 82, a Society of Thoracic Surgeons predicted risk of mortality (STS-PROM) score of 3%; and SYNTAX score 9. Around one in five people had multivessel disease.

Baseline characteristics were mostly well balanced between the two randomized groups, with the exception of the PCI group having more smokers and people with chronic obstructive pulmonary disease. The PCI group also had more lesions for revascularization.

Participating operators were urged to achieve complete revascularization of all PCI-eligible lesions. This was ultimately achieved in 89% of cases, the researcher said.

There were PCI procedure-related complications in 3% of patients.

Time spent from randomization to TAVR was a median 34 days in the add-on PCI group versus 25 days in the conservative treatment arm, according to Lønborg.

TAVR was done with a balloon-expandable heart valve in about 40% of cases. For people who may require PCI after TAVR, this could be the better choice compared with tall-frame, self-expanding valves, Mehta suggested.

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