Sacubitril/valsartan lowers pulmonary artery pressures at 30 days in HFrEF
In a cohort of patients with HF with reduced ejection fraction, those who received sacubitril/valsartan demonstrated decreased pulmonary artery pressures at 30 days compared with those who did not receive it, researchers reported.
“These data provide mechanistic support for an early effect of angiotensin receptor neprilysin inhibitors (ARNIs) on cardiac remodeling and clinical outcomes in HFrEF, and suggest a novel paradigm for investigating the hemodynamic effects of other pharmacologic agents in clinical practice,” Akshay S. Desai, MD, MPH, medical director of the Cardiomyopathy and Heart Failure Program at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, told Healio.
Desai said randomized controlled trials of ARNIs compared with ACE inhibitors in HF have highlighted favorable changes in cardiac remodeling and important reductions in HF-associated morbidity and mortality. “Early reductions in natriuretic peptides and atrial and ventricular volumes following initiation of neprilysin inhibition suggest a possible impact of neprilysin inhibition on intracardiac filling pressures,” he said. “Longitudinal access to ambulatory pulmonary artery pressure (PAP) data in the CardioMEMS PAS Post-Approval Study presented a unique opportunity to test this hypothesis.”
The post-approval study included 1,200 patients with chronic HF, NYHA class III symptoms and prior HF hospitalization who received an implantable PAP sensor for ambulatory hemodynamic monitoring (CardioMEMS, Abbott). Researchers assessed 30-day changes in PAP in patients newly initiated on sacubitril/valsartan (Entresto, Novartis) at a median of 168 days after device implantation.
The comparator group was composed of patients with HFrEF who were eligible but not initiated on sacubitril/valsartan within a matched 30-day period.
Overall, 96 patients received ARNI and 406 were in the comparator arm. Mean PAP before starting sacubitril/valsartan was 32.8 ± 10.5 mm Hg, which dropped to 29.9 ± 9.4 mm Hg at 30 days (P < .001). Patients with baseline mean PAP less than 30 mm Hg experienced no significant change in mean PAP (P = .14), whereas those with a baseline mean PAP of at least 30 mm Hg demonstrated a reduction (4.2 mm Hg; 95% CI, 5.7 to 2.6; P < .0001).
In other 30-day data, PAP reduction was greater for those in the sacubitril/valsartan arm, and no difference between groups was observed in the frequency of changes in other CV medicines.
The reason for sacubitril/valsartan reducing PAP so soon after initiation, Desai told Healio, starts with neprilysin breaking down a number of vasoactive peptides, including the biologically active natriuretic peptides ANP and BNP. “Accordingly, inhibition of neprilysin with sacubitril/valsartan may enhance circulating levels of these peptides which reduce systemic vascular resistance, increase venous capacitance and enhance natriuresis, with attendant reductions in intracardiac filling pressures,” he said.
For more information:
Akshay S. Desai, MD, MPH, can be reached at adesai@bwh.harvard.edu; Twitter: @akshaydesaimd.
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