File(s) under permanent embargo

Reason: Permanent publisher embargo

Effect of Transcatheter Aortic Valve Implantation vs Surgical Aortic Valve Replacement on All-Cause Mortality in Patients With Aortic Stenosis: A Randomized Clinical Trial.

journal contribution
posted on 21.06.2022, 09:59 authored by UK TAVI Trial Investigators, William D Toff, David Hildick-Smith, Jan Kovac, Michael J Mullen, Olaf Wendler, Anita Mansouri, Ines Rombach, Keith R Abrams, Simon P Conroy, Marcus D Flather, Alastair M Gray, Philip MacCarthy, Mark J Monaghan, Bernard Prendergast, Simon Ray, Christopher P Young, David C Crossman, John GF Cleland, Mark A de Belder, Peter F Ludman, Stephen Jones, Cameron G Densem, Steven Tsui, Manoj Kuduvalli, Joseph D Mills, Adrian P Banning, Rana Sayeed, Ragheb Hasan, Douglas GW Fraser, Uday Trivedi, Simon W Davies, Alison Duncan, Nick Curzen, Sunil K Ohri, Christopher J Malkin, Pankaj Kaul, Douglas F Muir, W Andrew Owens, Neal G Uren, Renzo Pessotto, Simon Kennon, Wael I Awad, Saib S Khogali, Maciej Matuszewski, Richard J Edwards, Bandigowdanapalya C Ramesh, Miles Dalby, Shahzad G Raja, Giovanni Mariscalco, Clinton Lloyd, Ian D Cox, Simon R Redwood, Mark G Gunning, Paul D Ridley

Importance

Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear.

Objective

To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk.

Design, setting, and participants

In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019.

Interventions

TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455).

Main outcomes and measures

The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation.

Results

Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75]).

Conclusions and relevance

Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year.

Trial registration

isrctn.com Identifier: ISRCTN57819173.

Funding

The study was funded by the National Institute for Health Research Health Technology Assessment Programme (project reference 09/55/63). Additional support was provided by the National Institute for Health Research Clinical Research Network. Excess treatment costs were paid by the NHS England in England, by the National Institute for Social Care and Health Research in Wales, and by the Chief Scientist Office and NHS Research Scotland in Scotland. The transcatheter aortic valves and surgical valves were procured through standard National Health Service commissioning processes. The research governance sponsor for the study was the University of Leicester.

History

Citation

JAMA. 2022;327(19):1875-1887. doi:10.1001/jama.2022.5776

Author affiliation

Department of Cardiovascular Sciences, University of Leicester

Version

AM (Accepted Manuscript)

Published in

JAMA

Volume

327

Issue

19

Pagination

1875 - 1887

Publisher

American Medical Association (AMA)

issn

0098-7484

eissn

1538-3598

Acceptance date

28/03/2022

Copyright date

2022

Spatial coverage

United States

Language

eng