RECOVERY: Early Surgery Best in Severe Asymptomatic AS? – Medscape

PHILADELPHIA New randomized trial results show early aortic valve replacement (AVR) resulted in a lower risk for operative mortality or death from cardiovascular causes compared with conservative care in asymptomatic patients with severe aortic valve stenosis.

Secondary analysis also showed a reduced risk for all-cause mortality, the researchers report.

The results, from the Randomized Comparison of Early Surgery versus Conventional Treatment in Very Severe Aortic Stenosis (RECOVERY) trial, were presented here at the American Heart Association (AHA) Scientific Sessions 2019 and were published online November 16 in the New England Journal of Medicine.

"Early surgical aortic valve replacement, as compared with conventional treatment, significantly reduced the risk of operative or cardiovascular mortality and death from any cause among asymptomatic patients with very severe aortic stenosis," Duk-Hyun Kang, MD, PhD, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, South Korea, told theheart.org | Medscape Cardiology.

"Our RECOVERY trial provides the evidence to support preemptive aortic valve replacement for asymptomatic severe aortic stenosis," he said.

Observers here, however, raised questions about the generalizability of these results, since the patients in the trial were relatively young, there was a high incidence of bicuspid aortic valve disease, there were few comorbidities, and operative risk was low, something the researchers also point out in their article.

"Thus, our trial population is quite different from the populations enrolled in TAVR [transcatheter aortic valve replacement] trials, and the results of our trial cannot be directly applied to early TAVR for asymptomatic severe aortic stenosis," the researchers conclude. Similarly, the results may not apply to lower-volume centers or to patients at higher operative risk.

AVR is the only effective therapy for severe aortic stenosis that is symptomatic, the authors write, and "despite limited data from randomized clinical trials, current guidelines recommend aortic-valve replacement because of the dismal nature of this disorder."

For the one third to one half of patients who are asymptomatic at diagnosis, though, the appropriate timing for intervention "remains controversial," they note.

"Based on the consensus opinion that the potential benefit of AVR to prevent sudden death may not be greater than the risk of AVR, watchful waiting is recommended for the vast majority of asymptomatic patients with severe aortic stenosis, with AVR planned once symptoms develop," Kang said.

Recent observational studies have suggested that early surgery is potentially beneficial in comparison with conventional treatment, he said, but these results might have been affected by baseline differences between treatment groups, treatment selection bias, or other unmeasured confounders.

"Only a randomized trial can reduce these limitations inherent to observational studies, and we conducted the first randomized trial to address the question of whether early AVR is preferable to a strategy in which AVR is deferred until symptoms develop," Kang said.

The RECOVERY trial aimed to compare long-term clinical outcomes of early surgical AVR with a conservative care strategy based on current guidelines in asymptomatic patients with severe aortic stenosis, defined as an aortic valve area of 0.75 cm2 with either an aortic jet velocity of 4.5 m/sec or a mean transthoracic gradient of 55 mmHg.

The primary endpoint was a composite of death during or within 30 days after surgery (operative mortality) or death from cardiovascular causes during follow-up. A major secondary endpoint was death from any cause. The mean peak aortic jet velocity was 5.1 0.5 m/sec, and the mean aortic valve area was 0.63 0.09 cm2.

Treatment groups were well balanced. The mean age of the patients was 64.2 9.4 years, and 49% were men. The cause of aortic stenosis was bicuspid aortic valve in 88 patients (61%), degenerative aortic valvular disease in 48 patients (33%), and rheumatic valvular disease in nine patients (6%).

Of the 73 patients assigned to early surgery, 69 underwent surgery (95%) within about 2 months after randomization. There was no operative mortality, Kang reported. "The median follow-up of our trial was 6.3 years, and no patients were lost to follow-up."

In the intention-to-treat analysis, which included all patients, one patient in the early surgery group and 11 patients in the conventional treatment group died from cardiovascular causes, he said. "The hazard ratio was 0.09, the number needed to treat to prevent one cardiovascular death within 4 years was 20 patients," he noted.

For the secondary endpoint of death from any cause, there were five such deaths in the early surgery group and 15 in the conventional treatment group. "The hazard ratio was 0.33, and the number needed to treat to save one life within 4 years was 16 patients," Kang said.

Table. RECOVERY: Primary and Secondary Outcomes by Intervention

The cumulative incidence of the primary endpoint, operative mortality or cardiovascular death, calculated by Kaplan-Meier analysis, was 1% at both 4 and 8 years in the early surgery group, vs 6% at 4 years, and 25.5% at 8 years in the conventional treatment group (P = .003).

The cumulative incidence of death from any cause was also lower in the early surgery group than in the conventional treatment group: 4% vs 10% at 4 years in the early surgery group vs conventional care, and 10% vs 32% at 8 years, Kang said.

Athena Poppas, MD, vice president of the American College of Cardiology (ACC) and professor of medicine at the Warren Alpert Medical School, Brown University, in Providence, Rhode Island, called the findings "very interesting and provocative, in that they had a high rate in the conservative group of sudden death, and that's certainly alarming. And these were clearly severe aortic stenosis by echo and not low-flow, low-gradient AS, which is another category."

In an older population, the surgical mortality would be higher and the morbidity would be higher, Poppas told theheart.org | Medscape Cardiology, "and so I don't think we can apply those findings to that group."

But the findings could be applied, for example, to the bicuspid valve group, for whom operative mortality should be very low, she said. "They had no operative deaths sort of confirming that it was a very healthy population. So I think it answered an important question for a narrow population of patients," she added, but how the findings should apply to older patients is still unclear.

In his remarks as invited discussant, Robert O. Bonow, MD, Northwestern University Feinberg School of Medicine in Chicago, Illinois, also touched on the generalizability of the results, particularly with respect to those patients in the TAVR trials.

"So the question would be, would these excellent results obtained in this single trial be transportable to the United States in large centers where sometimes the operative mortality is not zero and we do indeed have the risks of stroke as we follow our patients?" Bonow said.

Current AHA/ACC guidelines give a class IIa recommendation to aortic valve replacement for very severe aortic stenosis with a Vmax>5.5 m/sec, he noted.

"Does the current data move the playing field? Does it move the ball? Should we be talking about moving our threshold down to 4.5, or maybe increasing the class IIa [indications] up to class I?" he asked.

"I think we need to wait to see more data to support these excellent results from Dr Kang, but in the meantime, for those of us who see patients, one could argue again that the majority of these patients do come to a surgical endpoint within a very short period of time, so from a clinical management point of view, I think we see already the data suggesting we could move the ball forward, and now we have these excellent outcome data from Korea as well," Bonow said.

Similar points are made in an accompanying NEJM editorial by Patrizio Lancellotti, MD, PhD, University of Lige Hospital, Interdisciplinary Cluster for Applied Genoproteomics Cardiovascular Sciences, Centre Hospitalier Universitaire Sart-Tilman, Belgium, and Mani A. Vannan, MB, BS, Piedmont Heart Institute, Marcus Heart Valve Center, Atlanta, Georgia. They also point out that the population was younger, with fewer comorbidities and more bicuspid valves than was seen in current TAVR trials, and note that many of the patients in the trial would have met current IIa criteria for intervention.

"So although the trial by Kang et al has certainly emphasized the challenge of ascertaining valve-related symptoms in the real world, direct extension of these results to patients with asymptomatic severe aortic stenosis cannot be made at this time," Lancellotti and Vannan write.

They suggest waiting on results of ongoing trials of early TAVR in patients with asymptomatic severe aortic stenosis "for further guidance." Those trials include Aortic Valve Replacement versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis (AVATAR), Early Valve Replacement Guided by Biomarkers of LV Decompensation in Asymptomatic Patients with Severe AS (EVOLVED), Early Surgery for Patients with Asymptomatic Aortic Stenosis (ESTIMATE), and Evaluation of Transcatheter Aortic Valve Replacement Compared to Surveillance for Patients with Asymptomatic Severe Aortic Stenosis (EARLY TAVR).

The study was funded by the Korean Institute of Medicine. Kang reports receiving grants from the Korean Institute of Medicine during the conduct of the study. Lancellotti has disclosed no relevant financial relationships. Vannan reports reciving grants and nonfinancial support from Siemens and grants from Abbott, Medtronic, and Lantheus outside the submitted work. Bonow reports no relevant financial relationships.

N Engl J Med. Published online November 16, 2019. Abstract, Editorial

American Heart Association (AHA) Scientific Sessions 2019: Presented November 16, 2019.

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RECOVERY: Early Surgery Best in Severe Asymptomatic AS? - Medscape