What is the clinical evidence from this study?

Study design: Observational. Population: Aortic stenosis (n=23847). Intervention: Off-label TAVR vs. On-label TAVR. Primary outcome: 1-year mortality (HR 1.11, 95% CI 0.98-1.25, p=.11).

June 21, 2017

Trends and Outcomes of Off-label Use of Transcatheter Aortic Valve Replacement

Key Result

Off-label use of TAVR was associated with similar adjusted 1-year mortality compared to on-label use (HR 1.11; 95% CI 0.98-1.25; P=0.11), despite higher unadjusted mortality rates.

Study Design

Type

Observational (n=23,847)

Multicenter

Yes

Structured PICO

Does off-label use of TAVR increase mortality compared to on-label use in patients undergoing transcatheter aortic valve replacement?

Population

23,847 patients receiving commercially funded transcatheter aortic valve replacement (TAVR) in the United States across 328 sites, median age 84 years, 49.8% female.

Intervention

Off-label use of TAVR (defined as TAVR in patients with known bicuspid valve, moderate aortic stenosis, severe mitral regurgitation, severe aortic regurgitation, or subaortic stenosis).

Comparator

On-label use of TAVR (for severe aortic stenosis in patients who cannot undergo surgery and for patients at high operative risk).

Outcome

Frequency of off-label TAVR use and the association with in-hospital, 30-day, and 1-year adverse outcomes (mortality).hard clinical

Approximately 9.5% of TAVR procedures in the US are performed for off-label indications, which is associated with higher early mortality but similar adjusted 1-year mortality compared to on-label use.

Main Result

Effect estimate: HR 1.11 (95% CI 0.98-1.25)

Absolute Event Rate: 25.6% vs 22.1%

p-value: p=.11

Abstract

Importance: Transcatheter aortic valve replacement (TAVR) was approved by the US Food and Drug Administration for severe aortic stenosis in patients who cannot undergo surgery and for patients at high operative risk. Use of TAVR for off-label indications has not been previously reported. Objective: To evaluate patterns and adverse outcomes of off-label use of TAVR in US clinical practice. Design, Setting and Participants: Patients receiving commercially funded TAVR in the United States are included in the Transcatheter Valve Therapy Registry. A total of 23 847 patients from 328 sites performing TAVR between November 9, 2011, and September 30, 2014, were assessed for this study. Off-label TAVR was defined as TAVR in patients with known bicuspid valve, moderate aortic stenosis, severe mitral regurgitation, severe aortic regurgitation, or subaortic stenosis. Data were linked with the Centers for Medicare median age, 84 years interquartile range, 78-88 years), off-label TAVR was used in 2272 patients (9.5%). In-hospital mortality was higher among patients receiving off-label TAVR than those receiving on-label TAVR (6.3% vs 4.7%; P < .001), as was 30-day mortality (8.5% vs 6.1%; P < .001) and 1-year mortality (25.6% vs 22.1%; P = .001). Adjusted 30-day mortality was higher in the off-label group (hazard ratio, 1.27; 95% CI, 1.04-1.55; P = .02), while adjusted 1-year mortality was similar in the 2 groups (hazard ratio, 1.11; 95% CI, 0.98-1.25; P = .11). The median rate of off-label TAVR use per hospital was 6.8% (range, 0%-34.7%; interquartile range, 3.4%-12.1%), with hospitals in the highest tertile of off-label use associated with increased 30-day adverse cardiovascular events compared with the lowest tertile. However, this difference was not observed in adjusted 30-day or 1-year outcomes. Conclusions and Relevance: Approximately 1 in 10 patients in the United States have received TAVR for an off-label indication. After adjustment, 1-year mortality was similar in these patients to that in patients who received TAVR for an on-label indication. These results reinforce the need for additional research on the efficacy of off-label TAVR use.

Bookmark

View Full Paper