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

Abstract

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.

Figure 1.. Patient Selection, Allocation, and Flow in the UK Transcatheter Aortic Valve Implantation (UK TAVI) Trial for Aortic Stenosis

^aPatients were invited to participate after multidisciplinary team review and confirmation of eligibility. Participating sites maintained monthly screening logs of patients recommended for consideration for enrollment; however, some logs were missing, with an estimated overall shortfall of 22% (based on the number of patients randomized but not included in the screening logs). This would imply that the actual number of patients reviewed by the multidisciplinary team and invited to participate was in the region of 1740 rather than the stated figure of 1357, which was derived directly from the screening logs. Data regarding overall national TAVI and surgery activity during the relevant period are available from the relevant national audits.^{,, b}Randomization used minimization, including an 80% probabilistic element with stratification for the randomization site, age group (70-79 years vs ≥80 years), and the presence of coronary artery disease considered by the multidisciplinary team to require revascularization if the patient was randomized to receive surgery. ^cThree additional participants were treated as randomized but excluded from the per-protocol analysis (2 were treated >1 year after randomization and 1 withdrew from all follow-up).

Figure 2.. Time-to-Event Curves for the Primary Outcome and Major Secondary Outcomes

Kaplan-Meier survival analysis at 1 year after randomization. All patients were followed up to the time of an event, withdrawal from the study, or 1 year after randomization. The hazard ratios are specific to the 1-year outcomes. The P values were derived from a Cox proportional hazards model, which was adjusted for randomization minimization factors and used robust SEs to account for clustering of outcomes by randomization site. Cause of death (cardiovascular vs noncardiovascular) and stroke events were adjudicated by the end points and events committee, with reference to outcome definitions based on criteria from the Valve Academic Research Consortium-2 consensus document (eMethods 5 in Supplement 2). TAVI indicates transcatheter aortic valve implantation.