Transcatheter Aortic-Valve Replacement in Low-Risk Patients. Reply.
Michael J. Mack M.D.
Mack, M. J. and M. B. Leon (2019). “Transcatheter Aortic-Valve Replacement in Low-Risk Patients. Reply.” New England Journal of Medicine 381(7): 684-685.
Kaul’s major concern is that there were fewer primary end-point events in the Placement of Aortic Transcatheter Valves (PARTNER) 3 trial than in earlier trials. He states that the inclusion of rehospitalization in the composite primary end point led it to become the main driver for the superiority of TAVR and also introduced a bias against surgery owing to the number of concomitant procedures performed in the surgical group. In PARTNER 3, the primary end point was specifically chosen to account for the lower event rate expected in low-risk patients and was powered on the basis of anticipated event rates from previous PARTNER trials. The sample size assumed a composite end-point event rate of 16.6% in the surgery group and 14.6% in the TAVR group. In fact, the primary event rates were 15.1% and 8.5%, respectively, and all components of the composite end point directionally favored TAVR. Rehospitalization was included because we believe it is a meaningful adverse outcome in low-risk patients, and it has been used as the sole primary end point in other recent trials. The higher rate of concomitant procedures in surgery (26.4% vs. 7.9%), mentioned both by Kaul and by Perella and Anwar, is a reflection of real-world surgical practice. The heart team at each site concluded before randomization that either approach, surgery or TAVR, would yield the best possible outcome. Since those patients who had a concomitant procedure did not have a higher rate of primary end-point events, there was no bias against surgery. Data available at the 10-year follow-up should give further insight into the risks and benefits of each approach, especially among patients who underwent concomitant coronary revascularization. Baldetti et al. noted a higher incidence of new-onset LBBB among patients who underwent TAVR, which suggests the possibility of the unfavorable prognostic effect of mechanical dyssynchrony. We agree and have recently published an analysis of patients in the earlier, higher-risk trials that shows worse left ventricular systolic function and more adverse clinical outcomes in patients with new LBBB. Precisely for these reasons, all patients will be followed with clinical, echocardiographic, and electrocardiographic assessment annually for 10 years. Finally, Savas et al. express concern that the higher rate of mild paravalvular leak with TAVR may lead to increased late mortality, citing data from a PARTNER trial involving high-risk patients. Although we share their concern, subsequent analyses of intermediate-risk patients have not shown an increase in mortality with mild paravalvular regurgitation.4 Nonetheless, all patients will be carefully followed for 10 years to address this concern. (Authors’ response to several commentaries on their previously published studies: Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med 2019;380:1695-1705 and Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med 2016;374:1609-1620.)