Complete two-year follow-up data from the Evolut Low Risk trial, presented during a late-breaking trial session at EuroPCR 2021 (18–20 May, virtual), offer “reassuring” evidence on the outcomes of transcatheter aortic valve implantation (TAVI) in low-surgical risk patients, speakers at the virtual event commented. However, longer-term data are needed to better understand the merits of transcatheter or surgical interventions in low-risk aortic stenosis patients.
The Evolut Low Risk trial is a randomised, non-inferiority trial, in which TAVI with a self-expanding supra-annular bioprosthesis (CoreValve, Evolut R, or Evolut PRO; Medtronic) was compared with surgical aortic-valve replacement (SAVR) in patients who had severe aortic stenosis and were at low surgical risk. Patients enrolled in the trial are due to be followed out to ten years.
One-year data from the trial, presented at the PCR e-course in 2020, demonstrated that TAVI is non-inferior to SAVR for all-cause mortality or disabling stroke. Presenting the complete two-year data on behalf of the Evolut Low Risk trial investigators at EuroPCR 2021, John Forrest (Yale School of Medicine, New Haven, USA) reported at the virtual meeting that at two years TAVI remained non-inferior to surgery with regard to these primary endpoints.
Forrest told attendees that the as-treated cohort consisted of 1,414 patients, with TAVI attempted in 730 and surgery in 684 patients. Completed two-year follow-up was available for 97.3% in the TAVI group and 92.3% in the surgery group. At 12 months, the primary outcome occurred in 2.5% in the TAVI group vs. 4.3% in the surgical group (p=0.057), Forrest explained. At 24 months, the primary outcome occurred in 4.3% in the TAVI arm vs. 6.3% in the surgical group (p=0.084 for superiority, p<0.001 for non-inferiority), he noted.
The study group also examined the question of “catch-up” in outcomes between TAVI and surgery between 12 and 24 months. “In some of the recent low risk TAVI studies, there has been a question of catch-up of the surgical arm between 12 and 24 months, as it relates to the initial benefit of TAVI,” said Forrest. “We know with TAVI, because it is a less invasive procedure, we do have this trend towards benefit of mortality early on with that early separation of the curves. To better evaluate this in this study, we performed a landmark analysis and reset at 12 months and followed from 12 to 24 months.”
In this landmark analysis, the primary outcome occurred in 1.9% in the TAVI group vs. 2.1% in the surgical group (p=0.742); thereby indicating no late adverse catch-up phenomenon in the TAVI group between years 1 and 2. Also additionally reported, at two-years, TAVI with a self-expanding supraannular bioprosthesis was superior to surgery in regards to valve haemodynamics and prosthesis-patient mismatch. However, surgery was superior to TAVI in regards to the incidence of pacemaker implantation and mild paravalvular leak.
Following his presentation, Forrest was asked by session moderator Bernard Prendergast (St Thomas’ Hospital, London, UK), to comment on the implication of the results, and what reassurance they should provide to interventional cardiologists considering TAVI in low risk patients.
“There was a lot of criticism that the interventional community was reacting to one-year data,” said Prendergast. “We now have two-year follow-up both from PARTNER 3 and the Evolut Low Risk trial— what does this mean for practice and for guidelines, and how long do we need to wait until we are comfortable and reassured that we can provide TAVI in younger and lower risk patients with a durable outcome?”
Responding to these questions, Forrest said that the data should provide “reassurance” of the safety and efficacy of TAVI in low risk patients. However, he also commented that longer-term data will be vital to provide a greater level of insight.
“As we have moved to younger ages the longer-term outcomes become critically important,” Forrest said. “I also think that we need to be realistic. We are really going to be interested in five and 10-year outcomes, and potentially even thereafter, what happens to these valves when they eventually fail?
“Are superior haemodynamics going to give us longer valve durability in some way? Or, are there going to be other unforeseen things that come up 10 years out? We do not yet know those answers. This is one of the studies where it is critically important to follow these patients for a long period of time and patients in this study will be followed for 10 years.”
Putting the results into perspective, panellist Marie Claude Morice (Institut Hospitalier Jacques Cartier, Massy, France) said that there is now an “incredible amount of data” comparing TAVI and surgery across patients in different risk profiles.
“They show a lot of good news, in particular that mortality is decreasing, and stroke also, so that is very good news,” she commented. “They show also that the combined endpoint of mortality and stroke is clearly in favour of TAVI.”
However, she noted that the remaining question is the longevity of the valve. Summing up, she said: “What all that illustrates is that the tidal wave of TAVI success is continuing and that we can look optimistically into the future. What is the future? Is it now the non-symptomatic patients?”
In a press release, Medtronic said the results demonstrate that TAVI with the Evolut platform “trended the same or lower on all critical events” as surgery.
“Results from this landmark study reassure us that the positive outcomes presented using the Bayesian statistical analysis at ACC.19, before the full two-year outcomes were available, matched the actual two-year outcomes and thus was an extremely accurate and scientifically rigorous methodology that researchers can feel confident about moving forward,” said Jeffrey J Popma, vice president and chief medical officer for the Coronary & Renal Denervation business and the Structural Heart & Aortic business, which are part of the Cardiovascular Portfolio at Medtronic. “Furthermore, the Evolut TAVI platform continues to show it is a treatment option well-suited for lower-risk patients who are living longer and may be more active.”