The results of the PARTNER 3 and Evolut LR trials that looked at TAVR vs. surgical aortic valve replacement in low-risk patients with severe aortic stenosis do not support recommending TAVR for this population, according to a paper published Aug. 17 in the Journal of the American College of Cardiology.

Sanjay Kaul, MD, reviewed results of the PARTNER 3 and Evolut LR trials, which in 2019 led the U.S. Food and Drug Administration to expand the indication for TAVR to patients with severe aortic stenosis at low surgical risk. Kaul summarizes the methodology, analysis characteristics and results for the two trials, comparing them to earlier trials that looked at TAVR in intermediate- and high-risk populations.

Compared with trials in higher-risk groups, the sample sizes in the low-risk populations were smaller and the number of primary endpoint events was lower (193 in low-risk trials vs. 615 in high-risk trials). According to Kaul, this suggests an "insufficient quantum of evidence" to recommend TAVR in low-risk patients. Kaul also writes that the trial design for the low-risk cohorts was "less robust." He notes that PARTNER 2, which tested TAVR in an intermediate-risk group, had a primary endpoint of death or disabling stroke vs. a primary endpoint of death, any stroke or rehospitalization for PARTNER 3. In addition, PARTNER 3 had a shorter follow-up time and wider noninferiority margin. In addition, the low-risk trials had different key outcomes despite similar baseline cardiovascular risk, which could "challenge generalizability," Kaul writes.

According to Kaul, the "totality of evidence does not support endorsing TAVR as the preferred therapy" for low-risk patients." The "quantum of evidence" needed to extend TAVR guideline recommendations to these patients should "be based on stringent trial design utilizing unbiased primary endpoints and longer follow-up without modeling outcomes via imputation," he concludes.

"A balance needs to be struck between generating the most robust evidence possible in a reasonable time frame and with realistic funding, all while generating meaningful findings that are likely to impact clinical practice," Michael J. Mack, MD, MACC, and David H. Adams, MD, FACC, write in a Counterpoint. Controversy regarding the outcomes of comparative trials often concern the trial's design, which is often not widely known before a trial begins. It is thus, "imperative that all stakeholders scrutinize the various aspects of trial design and endpoints" early enough to allow investigators an opportunity to reconsider the design, and potentially make changes that would strengthen the study," they conclude.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and VHD, Interventions and Structural Heart Disease

Keywords: Aortic Valve, Risk Factors, Transcatheter Aortic Valve Replacement, Cardiovascular Diseases, United States Food and Drug Administration, Aortic Valve Stenosis, Heart Valve Prosthesis, Stroke, Cardiology, National Cardiovascular Data Registries, STS/ACC TVT Registry

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