Early surgical aortic valve replacement (SAVR) was associated with a lower composite rate of adverse events in comparison with a more conservative treatment strategy for patients with severe, mainly degenerative aortic stenosis (AS) and normal left ventricular (LV) function, according to new trial results.
Marko Banovic, MD, PhD, lead investigator of the AVATAR trial and an associate professor of cardiology at the University Clinical Center of Serbia and the University of Belgrade Medical School in Serbia, presented these results Saturday at the American Heart Association Scientific Sessions 2021 virtual meeting. The results were simultaneously published online in Circulation.
The decision to operate on an asymptomatic patient with severe AS and normal LV function still has no consensus. Observational findings showing increased mortality and morbidity have challenged the strategy of “watchful waiting,” Banovic said.
He added that the RECOVERY randomized trial suggested that early valve surgery conferred a benefit in critical AS and in patients with a high prevalence of bicuspid etiology.
The AVATAR trial was initiated to evaluate the safety and efficacy of early SAVR in asymptomatic patients with severe aortic stenosis and normal LV function. Severe AS was defined as valve area ≤1 cm2 with aortic jet velocity >4 m/s or a mean transaortic gradient ≥40 mmHg, the investigators reported in the manuscript.
AVATAR is a physician-initiated, prospective, multicenter, randomized, open-label, parallel-group trial that was performed at nine medical centers in 7 European countries. The study randomized 157 patients to elective SAVR or conservative treatment (watchful waiting with guideline-directed management).
The trial included adults 18 years or older with severe AS, without symptoms (which was confirmed by exercise testing), and a Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score <8%. Main exclusion criteria were symptoms confirmed by exercise, LV ejection fraction <50% at rest, very severe (critical) AS (aortic jet velocity >5.5 m/s), need for aortic or other valve surgery, previous cardiac surgery, and major comorbidities or life expectancy <3 years.
The primary endpoint was a composite of all-cause mortality and major adverse cardiac events (MACE; comprising acute myocardial infarction, stroke and unplanned heart failure hospitalization requiring intravenous diuretics or inotropes). Secondary endpoints included components of the primary endpoint.
A total of 197 patients were assessed for eligibility between June 2015 and September 2020, of whom 40 were excluded (26 did not meet inclusion criteria, and 14 declined to participate). Of the 157 patients who were randomized, 79 were assigned to conservative treatment and 78 to early surgery. All of the conservative-arm patients were included in the intention-to-treat (ITT) and additional analysis, but six patients in the early surgery arm did not receive the allocated intervention, leaving all 78 in the ITT analysis and 72 in the additional analysis.
At baseline, the patients had an average age of 67 years, 57% were men, and their median STS-PROM score was 1.7%. AS was caused by degenerative valvular disease in 133 patients (84.7%), bicuspid aortic valve in 22 patients (14.0%) and rheumatic valvular disease in two patients (1.3%).
Of the 72 patients who underwent SAVR, 53% received a mechanical valve and 47% a bioprosthetic valve. The median time from randomization to surgery in the early surgery group was 55 days (interquartile range [IQR]: 36-79 days). In the conservative group, 25 patients underwent surgery, and 40% of them received a mechanical valve. The median time from randomization to surgery in the conservative group was 400 days (IQR: 191-619 days).
Banovic and co-authors reported that enrollment was lower than expected but the prespecified number of events (at least 35) was reached in October 2020 because of longer follow-up. On Nov. 1, 2020, the Data Safety Monitoring Board advised that the trial stop enrolling patients because of this.
Median follow-up was 28 months in the early surgery group and 35 months in the conservative group. The study recorded a total of 39 events, 13 (16.6%) in the early surgery group and 26 (32.9%) in the conservative treatment arm. A primary ITT analysis showed that the early surgery group had a significantly lower incidence of the primary composite endpoint than the conservative treatment group (15.2% vs. 34.7%; hazard ratio [HR]: 0.46; 95% confidence interval [CI]: 0.23-0.90; p=0.02).
Banovic said during his presentation that the benefit for early surgery started to appear at about 11 months post-procedure, and this benefit was sustained, or in some cases widened, through 4-year follow-up, according to a Kaplan-Meier estimate.
Turning to secondary endpoints, the early surgery group had a significantly lower incidence of the composite of all-cause mortality and heart failure hospitalization (HR: 0.40; 95% CI: 0.19-0.84; log-rank p = 0.013).
Banovic said during the presentation that it appeared the difference in the primary composite endpoint was driven by all-cause mortality (early surgery n=9 vs. conservative n=16) and heart failure hospitalization (early surgery n=1 vs. conservative n=7). A Kaplan-Meier estimate of the composite of all-cause mortality and heart failure hospitalization did show a significantly lower rate in the early SAVR arm (HR: 0.40; 95% CI, 0.19-0.84; log-rank p=0.013).
The other endpoints, including intraoperative mortality, repeated MACE, thromboembolic complication and major bleeding) showed no significant difference between the groups.
Banovic summarized by saying that the largest randomized trial in low-risk, asymptomatic patients with severe AS and normal LV function showed that early surgery was associated with a lower incidence of the primary composite endpoint as compared to conservative treatment.
He added that intraoperative mortality in the early surgery group (1.4%) was in line with the anticipated mortality for elective isolated SAVR.
“The findings advocate for early surgery once aortic stenosis becomes significant, regardless of symptoms,” Banovic said.