Heart failure

Edwards-backed Corvia fails pivotal heart failure trial, but clings to subgroup efficacy signal

Diving Brief:

  • Atrial shunt therapy from Corvia Medical failed to improve cardiovascular disease outcomes in patients with heart failure. Edwards Lifesciences Secure the exclusive right to acquire Corvia in 2019.
  • The pivotal trial randomized 626 patients with symptomatic heart failure to receive the Corvia atrial shunt or a sham procedure. There were no differences between the groups on the primary composite endpoint, which examined outcomes such as cardiovascular deaths, or any individual component of the composite endpoint.
  • Yet researchers have linked shunting to a beneficial effect on heart failure events in certain predefined patient subgroups, such as those with pulmonary vascular resistance (PVR) to normal exercise. Investigators published the results in The Lancet.

Overview of the dive:

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

The shunt, a penny-sized device implanted in 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 treat the high pressure that causes the symptoms of heart failure.

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

Compared to the composite endpoint, the shunt was no better than the sham procedure. The shunt also did not improve the results obtained by the sham procedure compared to any of the individual measures that made up the composite endpoint.

With the clinical trial missing its primary endpoint, Corvia turned to analyzes of predefined patient subgroups to prove the effectiveness of its shunt. Corvia focused on patients without pacemakers who had PVR on normal exercise, indicating the absence of pulmonary vascular disease (PVD).

In this subgroup, shunt recipients had 0.12 heart failure events per year, compared to 0.22 events in the control group. The difference between the two results reached statistical significance. Corvia also demonstrated a “clinically meaningful” improvement of 5.5 points in patient-reported outcomes. Other studies used a 5-point improvement in grading small significant changes in heart failure status.

Barry Borlaug, a professor and cardiologist at the Mayo Clinic, said in a statement that previous research had shown that 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 this patient cohort.

“Although further studies are needed, with appropriate patient selection, atrial shunt may be an excellent option for [heart failure with preserved ejection fraction] patients without any form of PVD,” Borlaug said. “In REDUCE LAP-HF II, treated patients with exercise-confirmed normal pulmonary vasculature had a significantly higher likelihood of clinical benefit than the sham control.

Shunt and sham treatment were performed comparably on a composite safety endpoint.