An atrial shunt device did not improve health status or reduce the total rate of heart failure (HF) events in patients with HF and ejection fraction of 40% or greater, according to study findings published in the Lancet.
These findings were the primary efficacy and safety results from the phase 3, randomized, double-blind, sham-controlled REDUCE LAP-HF II trial (Clinicaltrials.gov identifier: NCT03088033). Trial participants were aged 40 years or older, with symptomatic HF and an ejection fraction of 40% or greater. Eligible participants also had evidence of pulmonary capillary wedge pressure during exercise of 25 mm Hg or higher and exceeding right atrial pressure by 5 mm Hg or more. The patients were randomly assigned 1:1 to receive the shunt device or a sham procedure.
The primary efficacy endpoint was a hierarchical composite of cardiovascular death or nonfatal ischemic stroke up to 12 months after randomization; rate of total HF events up to 24 months postrandomization, assessed when the last randomized patient completed 12 months of follow-up; and change in Kansas City Cardiomyopathy Questionnaire overall summary score from baseline to 12 months.
A total of 1072 participants were enrolled from May 25, 2017, to July 24, 2020, of whom 626 were assigned to receive the atrial shunt device (median age, 73 years; 64% female; 90% White) or sham procedure (median age, 72 years; 59% female; 91% White).
The primary efficacy endpoint (win ratio 1.0 [95% CI, 0.8-1.2]; P = .85) was not different in the 2 groups, and no differences were observed between the groups for the individual components of the primary endpoint.
A differential effect of shunt device treatment was found in the following subgroups based on prespecified subgroup analyses: sex (pinteraction =.02), right atrial volume index (Pinteraction =.012), and pulmonary artery systolic pressure at 20W exercise (Pinteraction=.002).
No differences were found between the 2 groups regarding the composite safety endpoint, although patients who received shunt placement were more likely to have a major cardiac event (cardiac death, myocardial infarction, cardiac tamponade, or emergency cardiac surgery) in the 12 months after the index procedure vs those who had the sham procedure (4% vs 1%, respectively; P =.025).
The researchers noted that the peak exercise pulmonary vascular resistance (PVR) subgroup analyses were done post hoc and should be considered exploratory. Also, patients with major risk factors for increased mortality in HF and preserved ejection fraction and HF and mildly reduced ejection fraction were excluded, which could have led to the lower than expected mortality rate.
“Placement of an atrial shunt device did not result in a reduction in total rate of [HF] events or improvement in health status,” wrote the investigators. “However, treatment efficacy differed by presence or absence of pulmonary vascular disease unmasked by exercise; patients with no evidence of pulmonary vascular disease during exercise appeared to benefit from the device whereas patients with elevated PVR during exercise had worse outcomes.”
Disclosure: The study was funded by Corvia Medical. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Shah SJ, Borlaug BA, Chung ES, et al. Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial. Lancet. Published online February 1, 2022. doi: 10.1016/S0140-6736(22)00016-2