TAVR for Low-Risk Patients Is Safe, Effective, and Durable Out to 5 Years

Mid-term follow-up after transcatheter aortic valve replacement (TAVR) in low-risk surgical patients continues to show promise in comparison with surgical aortic valve replacement (SAVR).^1,2 In low-risk patients with severe symptomatic aortic stenosis (AS), TAVR is safe, effective, and durable out to 5 years, although there are some important caveats.

The original results of the PARTNER 3 (SAVR vs TAVR with the Edwards balloon-expandable valve [BEV]) and Evolut Low Risk (SAVR vs TAVR with the Medtronic self-expandable valve [SEV]) trials showed remarkable short-term results with TAVR over SAVR in low-risk patients with severe symptomatic AS, prompting the US Food and Drug Administration approval of both valve platforms in this patient population. However, uncertainty about long-term outcomes reduced initial enthusiasm, particularly for low-risk patients with longer expected longevities and fewer competing comorbidities.

The PARTNER 3 trial randomized 1000 patients with severe, symptomatic AS and low surgical risk to either SAVR (n=497) or TAVR (n=503) using the Edwards BEVs. One-year results indicated superiority of TAVR over SAVR, with a 6.6% absolute reduction in the primary composite of death, stroke, or rehospitalization with TAVR. Although the inclusion of rehospitalization has been scrutinized, TAVR was associated with significant reduction in each of the individual end point components.

Now, at 5 years, there is no significant different in the primary composite end point for TAVR versus SAVR (Kaplan-Meier estimates, 22.8% in the TAVR group vs 27.2% in the surgery group; difference, −4.3 percentage points; 95% CI, −9.9 to 1.3; P=.07). There is also no difference in the second primary end point, a hierarchical composite of death, disabling stroke, nondisabling stroke, and the number of rehospitalization days (win ratio, 1.17; 95% CI, 0.90-1.51; P=.25).

Of note, there were numerically more deaths in the TAVR arm (10.0%) than in the SAVR arm (8.2%), though the difference did not meet statistical significance. The Kaplan-Meier curves for all-cause mortality had favored TAVR in the short-term but crossed at approximately 3 years and now seem to continue diverging in favor of SAVR. However, mortality data is muddled by excess loss of follow-up in the SAVR group, and a vital status “sweep” analysis to account for lost follow-up seems to narrow this gap (estimated 5-year mortality, 10.2% with TAVR vs 9.0% with SAVR). The possibility of attrition bias is perhaps supported by the fact that the mortality difference was driven by noncardiovascular causes, which are less heavily adjudicated.

Rates of stroke (Kaplan-Meier estimate, 5.8% in the TAVR group vs 6.4% in the SAVR group) and rehospitalization (13.7% for TAVR vs 17.4% for SAVR) remained numerically, though not significantly, lower with TAVR. Reassuringly, there was no signal to suggest issues with valve durability. There were no significant differences in aortic valve gradients (12.8 mmHg with TAVR vs 11.7 mmHg with SAVR) or bioprosthetic valve failure as defined by the Valve Academic Research Consortium 3 criteria (3.3% with TAVR vs 3.8% with SAVR).

The Evolut Low Risk trial randomized 1468 patients with severe AS and low surgical risk to undergo TAVR with a Medtronic self-expanding valve (n=730) or SAVR (n=684). The 24-month estimated incidence of the primary end point, a composite of death or disabling stroke, was 5.3% with TAVR and 6.7% with surgery, meeting noninferiority. Now, the 4-year follow-up data on 94.7% of TAVR patients and 89.2% of SAVR patients have been reported as a research letter published in the Journal of the American College of Cardiology. At 4-year follow-up, the primary end point of all-cause mortality or disabling stroke had occurred in 10.9% of TAVR patients versus 14.1% of SAVR patients (hazard ratio, 0.74; 95% CI, 0.54-1.00; P=.05).

In contrast to the PARTNER 3 trial, the Kaplan-Meier curves and the absolute difference continue to diverge in favor of TAVR in the Evolut Low Risk trial. Rates of the individual components of the primary end point have remained numerically lower in the TAVR group (mortality, 9.0% vs 12.1%; disabling stroke, 2.9% vs 3.8%). TAVR patients continue to have better valve hemodynamics with lower aortic valve mean gradients (9.8 +/- 5.5 mmHg vs 12.1 +/- 5.4 mmHg; P<.001) and larger effective orifice areas (2.1 +/- 0.6 cm² vs 2.0 +/- 0.6 cm²; P<.001). There was no difference in moderate or greater paravalvular regurgitation. Notably, the TAVR group did have significantly greater new permanent pacemaker implantation rates (24.6% vs 9.9%; P<.001).

The cause for different signals for mid-term mortality with TAVR versus SAVR within the PARTNER 3 and Evolut Low Risk trials is unclear. Comparisons between the 2 trials are fraught with challenges (including different patient cohorts indicated by difference in mortality in the surgical arms) and should not be made. These mid-term data from the 2 trials continue to support the use of TAVR with both BEVs and SEVs in low-risk patients. We can comfortably tell these patients that TAVR safety, efficacy, and durability appear similar to surgery out to 4 to 5 years. However, this timeframe is not yet nearly long enough for younger and lower-risk patients. We all await the 10-year follow-up data with great anticipation.

References

1. Mack MJ, Leon MB, Thourani VH, et al; PARTNER 3 investigators. Transcatheter aortic-valve replacement in low-risk patients at five years. N Engl J Med. 2023. doi:10.1056/NEJMoa2307447
2. Forrest JK, Deeb GM, Yakubov SJ, et al. 4-year outcomes of patients with aortic stenosis in the Evolut. J Am Coll Cardiol. 2023. doi:10.1016/j.jacc.2023.09.813