Dive Brief:

• Corvia Medical's atrial shunt therapy has failed to improve cardiovascular disease outcomes in heart failure patients. Edwards Lifesciences secured the exclusive right to acquire Corvia in 2019.
• The pivotal trial randomized 626 patients with symptomatic heart failure to receive Corvia's atrial shunt or a sham procedure. There were no differences between the groups on the primary composite endpoint, which looked at outcomes such as cardiovascular death, or any individual component of the composite endpoint.
• Still, investigators did link the shunt to a beneficial effect on heart failure events in certain prespecified subgroups of patients, such as individuals with normal exercise pulmonary vascular resistance (PVR). The investigators published the results in The Lancet.

Dive Insight:

Edwards helped put Corvia on the map in 2019 when it paid $35 million for the right to buy the business. Corvia received breakthrough device designation from the FDA later that year, positioning it to work closely with the agency as it advanced a treatment aimed at an underserved group of patients with mid-range ejection fraction heart failure.

The shunt, a dime-size device implanted during a minimally invasive procedure, is designed to create a passage between the left and right atria. By allowing the left atrium to decompress, the device could address the elevated pressure that drives heart failure symptoms.

Corvia ran REDUCE LAP-HF II to put that idea to the test. The study enrolled symptomatic heart failure patients who had an ejection fraction of at least 40% and assessed them against a composite primary endpoint that looked at cardiovascular death or non-fatal ischemic stroke at 12 months, the rate of total heart-failure events up to 24 months and change in a patient-reported outcome score at 12 months.

Against the composite endpoint, the shunt was no better than the sham procedure. The shunt also failed to improve on the outcomes achieved by the sham procedure against any of the individual measures that made up the composite endpoint.

With the clinical trial missing its primary endpoint, Corvia looked to analyses of prespecified subgroups of patients for evidence of the efficacy of its shunt. Corvia focused on patients without pacemakers who had normal exercise PVR, indicating the absence of pulmonary vascular disease (PVD).

In that subgroup, recipients of the shunt had 0.12 heart failure events a year, compared with 0.22 events in the control group. The difference between the two results reached statistical significance. Corvia also highlighted a "clinically meaningful" 5.5-point improvement on the patient-reported outcome. Other studies have used a 5-point improvement to classify small significant changes in heart failure status.

Barry Borlaug, a professor and cardiologist at Mayo Clinic, said in a statement that earlier research had shown patients with significant PVD would be "very unlikely" to benefit from an atrial shunt. Still, Borlaug is encouraged by the evidence of efficacy outside of that cohort of patients. 

"While further study is needed, with appropriate patient selection, atrial shunting may be a great option for [heart failure with preserved ejection fraction] patients without any form of PVD," Borlaug said. "In REDUCE LAP-HF II, treated patients with normal pulmonary vasculature confirmed through exercise, had a significantly greater likelihood of clinical benefit than sham control."

The shunt and sham treatment performed comparably on a composite safety endpoint.