REDUCE LAP-HF II RCT: Corvia Medical, Inc, a company dedicated to transforming the treatment of heart failure (HF), today announced results from its REDUCE LAP-HF II randomized clinical trial, investigating the safety and efficacy of the Corvia® Atrial Shunt in heart failure patients with preserved (HFpEF) or mildly reduced (HFmrEF) ejection fraction.
While the overall outcome of the trial was neutral, the data suggests patients with normal exercise pulmonary vascular resistance (PVR) and without a pacemaker, represent a responder group that derives significant clinical benefit, making atrial shunting the first implantable therapy to demonstrate effectiveness in HFpEF.
Results were presented today at the Technology and Heart Failure Therapeutics (THT) 2022 conference and primary results were published online in The Lancet. Publication of the responder group analysis is pending.
“In this first-of-its-kind device trial for a complex and heterogenous type of heart failure, we have identified a large potential responder population with meaningful clinical benefit. The ability to predict responders and non-responders is ground-breaking and has significantly advanced our understanding of the role of atrial shunting in HFpEF,” said Sanjiv Shah, MD, Professor of Medicine, Director of Research for the Bluhm Cardiovascular Institute, and Director of the HFpEF Program at Northwestern University Feinberg School of Medicine and co-principal investigator of the REDUCE LAP-HF II trial.
The REDUCE LAP-HF II RCT is the world’s first phase III trial to evaluate an atrial shunt in heart failure patients to reduce HF symptoms, decrease HF-related hospitalizations and improve quality of life through a reduction in left atrial pressure (LAP). A total of 626 patients were randomized at 89 centers across the US, Canada, Europe, Australia, and Japan.
Patients with normal exercise PVR, indicating the absence of pulmonary vascular disease (PVD), and without a pacemaker, derived significant clinical benefit, including a reduction in heart failure events compared to sham (0.12 vs. 0.22 events per patient-year, p=0.007) and a significant and clinically meaningful difference in health status improvement over sham (+5.5 points) as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score.1
“Prior to this study, we knew patients with significant PVD would be very unlikely to benefit from atrial shunt treatment. However, we didn’t fully appreciate the critical role that invasive exercise phenotyping may have in uncovering the degree of PVD that allows patients to benefit from atrial shunting,” added Barry Borlaug, MD, Professor of Medicine and Director of Circulatory Failure Research at Mayo Clinic.
He notes, “While further study is needed, with appropriate patient selection, atrial shunting may be a great option for HFpEF patients without any form of PVD. 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, with a lower HF event rate and a significant and clinically meaningful KCCQ improvement.”
More than 26 million people in the world have heart failure,2 and over half of those have HFpEF,3 which has been described as the largest unmet clinical need in cardiovascular medicine. “These data have important implications not only for the Corvia Atrial Shunt, but for ongoing and future trials utilizing atrial shunt devices and procedures to treat heart failure,” stated Martin Leon, MD, Professor of Medicine and Director of Interventional Cardiovascular Care at Columbia University Irving Medical Center and co-principal investigator of the REDUCE LAP-HF II trial.
“We are proud that REDUCE LAP-HF II has led us to a major clinical breakthrough in HFpEF and we are working closely with our clinical advisors and regulators to expand access to this novel therapy,” said Jan Komtebedde, Senior Vice President and Chief Medical Officer of Corvia Medical. Added George Fazio, CEO of Corvia Medical, “For the past 12 years, Corvia Medical has been dedicated to bringing atrial shunting to the millions of heart failure patients who might benefit, and we are now one giant step closer to making our mission a reality.”
- REDUCE LAP-HF II 12-Month Primary Endpoint Report Addendum, Baim Institute 2022-01-18.
- Savarese G, Lund LH. Global Public Health Burden of Heart Failure. Card Fail Rev. 2017;3(1):7-11.
- Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006;355:251-259.