RECOVERY

Purpose: To compare the long-term clinical outcomes of early surgery to conventional treatment in asymptomatic patients with severe AS.

Trial Design: N=145 patients with severe AS randomized to early surgery or to guideline recommended conservative care. Multicenter, randomized 1:1, prospective, open-label. Follow-up 4 years after last patient enrolled. Mean age 64 years.

Composite Primary Endpoint: Operative mortality and CV death during follow-up.

Results: Lower composite of operative and CV death during follow-up, as well lower all-cause mortality in the early aortic valve surgery patients compared to the conventional treatment group.

Recommended:

• RECOVERY Abstract
• Duk-Hyun Kang's presentation slides (PDF)
• Published inNEJM: Early Surgery or Conservative Care for Asymptomatic Aortic Stenosis

Comparisons are early AVR versus conventional treatment

Primary Endpoint:

• Operative mortality or cardiovascular death: 1 (1.4%) vs 11 (15.3 %) [HR 0.12 (95% CI 0.02 – 0.72) p=0.02]

Secondary Outcomes:

• All-cause mortality:
  5 (6.8%) vs 15 (20.8%) [ 0.33 (95% CI 0.12 – 0.90); p=0.03]
• Clinical thromboembolic events (stroke + myocardial infarction):
  1 (1.4%) vs 4 (5.6%) [ 0.30 (95% CI 0.04 – 2.31); p=0.25]
• Repeat aortic valve surgery:
  0 (0) vs 2 (2.8%) [ 0.19 ( 95% CI 0.10 – 8.00); p=0.39]
• Hospitalization for heart failure:
  0(0) vs 8 (11.1%) [ 0.05 (95% CI 0.00 – 1.05); p=0.054]

Safety Endpoint: Not reported

Impression
Early surgical AVR (vs. conservative management) significantly reduced the rates of operative or cardiovascular death, and death from any cause in asymptomatic patients with very severe AS.

Related Science

• Otto, Catherine M., et al. "Prospective study of asymptomatic valvular aortic stenosis: clinical, echocardiographic, and exercise predictors of outcome." Circulation 95.9 (1997): 2262-2270.
• Monin, Jean-Luc, et al. "Risk score for predicting outcome in patients with asymptomatic aortic stenosis." Circulation 120.1 (2009): 69-75.
• Gada, Hemal, et al. "Quality-of-life implications of immediate surgery and watchful waiting in asymptomatic aortic stenosis: a decision-analytic model." Circulation: Cardiovascular Quality and Outcomes 4.5 (2011): 541-548.

Trial Design

• Multicenter, randomized, parallel-group, open-label trial, phase 3
• N=145
  • Early Surgery (N=73)
  • Conventional Treatment (N=72)
• Setting: Not reported
• Enrollment: July 2010 – April 2015
• Median follow-up: 6.2 years
• Analysis: Intention-to-treat

Trial Population

• Inclusion criteria:
  • Age 20 to 80 years
  • Asymptomatic patients with severe AS assessed by means of transthoracic echocardiography (AV area of 0.75 cm2 or less fulfilling one of the following criteria: a peak aortic jet velocity of 4.5 m/s or more, or a mean transaortic gradient of 50 mmHg or more)

• Exclusion criteria:
  • Patients with severe aortic stenosis and symptoms including exertional dyspnea, syncope, presyncope or angina
  • Left ventricular ejection fraction < 50%
  • Moderate or severe aortic regurgitation
  • Significant mitral valve disease or previous cardiac surgery.
  • Patients with non-specific symptoms and a positive exercise test
  • Age > 80 years
  • Poor medical condition, such as presence of malignancy

• Baseline characteristics:
  • Demographics: Mean age 64.2±9.4 years and 49.0% were men.
  • Etiology of AS: Bicuspid in 88 patients (60.7%), degenerative in 48 (33.1%), and rheumatic in 9 (6.2%).
  • Co-morbidities: Prevalence of Coronary artery disease between Early AVR vs conventional treatment arm was 6.9% vs 1.7 % p=0.22
  • Echocardiographic parameters: The peak aortic jet velocity averaged 5.1±0.5 m/sec; the mean transaortic pressure gradient was 63.5±13.5 mmHg; and the mean AV area was 0.63±0.09 cm2.

Aortic stenosis (AS) is the most common valve disease leading to surgery in developed countries, with a growing prevalence due to the aging population. While one-third to a half of patients with severe AS are asymptomatic at the time of diagnosis, there has been no proof that AVR improves outcome in asymptomatic patients with severe AS and optimal timing of intervention for these patients remains controversial (1). The two sets of consensus guidelines for the performance of early surgery on the basis of severity of AS are different, reflecting controversy. According to the 2014 AHA/ACC guidelines, it is reasonable to consider elective AVR in asymptomatic patients with very severe AS (aortic velocity =5.0 m/s) rather than waiting for symptom onset, whereas the 2017 ESC guidelines recommend watchful waiting in asymptomatic patients without very severe AS (aortic velocity >5.5 m/s), because early surgery is unlikely to be beneficial (2, 3). However, the evidence base for these recommendations is insufficient and the current conservative strategy has never been compared with early AVR in a randomized trial, which is needed to resolve this continuing clinical conundrum.

Interventions

• Patients randomized 1:1 to early aortic valve replacement (within 2 months of randomization) or matching conventional treatment according to current guidelines
• Adjudication of all outcome events performed by an independent clinical endpoints committee unaware of trial group assignments and lipid levels
• An independent data and safety monitoring committee oversaw the study and performed two pre-specified interim efficacy reviews

Outcomes/Endpoints
Comparisons are early AVR versus conventional treatment

Primary Outcome:

• Operative mortality or cardiovascular death

Secondary Endpoint:

• All-cause mortality
• Clinical thromboembolic events (stroke + myocardial infarction)
• Repeat aortic valve surgery
• Hospitalization for heart failure

Sponsor(s)/Collaborator(s): Asan Medical Center, Korea Institute of Medicine

TAVR, aortic stenosis, direct oral anticoagulants, dual antiplatelet, stroke, myocardial infarction, bleeding, thrombosis, embolism, echocardiography, surgery, survival

Aortic valve replacement; Transcatheter aortic valve replacement; Severe aortic stenosis; TAVR UNLOAD trial