Entresto builds clinical evidence for 'heart failure with ejection fraction rate exceeding 40%’
Novartis' angiotensin receptor-neprilysin inhibitor (ARNI) heart failure treatment Entresto (sacubitril/valsartan) has reduced hospitalization rates in patients with newly diagnosed (de novo) heart failure with mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF).
Novartis Korea said Thursday that such an analysis was presented at the American College of Cardiology (ACC)’s 73rd Annual Scientific Session & Expo, which was held from April 6 to 8.
The study was a retrospective comparative analysis of 82,664 patients with newly diagnosed HFmrEF and HFpEF who received a new prescription for Entresto or an ACE inhibitor/ARB from Jan. 1, 2016, to March 31, 2020, using data from Optum's electronic health record (EHR).
The analysis of 458 patients prescribed Entresto and 916 patients prescribed ACE inhibitors/ARBs showed a reduction in all-cause and cardiovascular hospitalizations in the Entresto group.
The all-cause hospitalization rate was 0.79 hospitalizations/person-year in the Entresto arm compared to 1.24 hospitalizations/person-year in the ACE inhibitor/ARB arm (incidence rate ratio: 0.73, 95 percent confidence interval: 0.59-0.92; p=0.006).
The cardiovascular hospitalization rate was 0.65 hospitalizations/person-year in the Entresto arm compared to 1.1 hospitalizations/person-year in the ACE inhibitor/ARB arm (incidence rate ratio: 0.70, 95 percent confidence interval: 0.55-0.88; p=0.002).
The results were consistent across key subgroups, including older patients and those with comorbidities, with a median follow-up of 391 days in the Entresto arm and 553 days in the ACE inhibitor/ARB arm.
Two subgroup analyses from the Phase 3 Entresto trial in HFpEF (PARAGLIDE-HF) were also presented at the meeting.
The two analyses confirmed positive changes in time-mean NT-proBNP from baseline in inpatient and outpatient, newly diagnosed, and chronic heart failure populations, showing consistent disease improvement regardless of treatment site or disease severity.
In the first analysis of PARAGLIDE-HF study participants with worsening heart failure within 30 days, separated into inpatients and outpatients, Entresto demonstrated improvements in NT-proBNP levels, a key biomarker reflecting heart function abnormalities, compared to valsartan.
NT-proBNP levels in the Entresto arm were reduced by 14 percent (95 percent CI -5 percent to 30 percent, p=0.14) in inpatients (324 patients, 70 percent in the Entresto arm and 162 in the valsartan arm) and 13 percent (95 percent CI -9 percent to 30 percent, p=0.22) in outpatients (142 patients, 30 percent in the Entresto arm and 71 in the valsartan arm).
Analyzing time-averaged NT-proBNP changes at the fourth and eighth weeks, stratifying patients with newly diagnosed versus chronic heart failure, confirmed the benefit of Entresto vs. valsartan (new diagnosis: Entresto 0.61 vs. valsartan 0.75/ chronic: Entresto 0.61 vs. valsartan 0.75).
"The reduced hospitalization rate and improved outcomes demonstrated by Entresto are very encouraging given the nature of HFmrEF and HFpEF patients with repeated hospitalizations," said Professor Shim Chi-young of the Department of Cardiology at Severance Hospital, also an academic director at the Korea Society of Heart Failure. “We expect Entresto's position as a recommended first-line treatment for HF with reduced left ventricular ejection fraction (HFrEF) to be further strengthened in patients with lower-than-normal heart rates."
Entresto received expanded health insurance coverage in Korea in 2022 as a first-line treatment for inpatients with acute heart failure, with an additional indication for chronic heart failure patients with lower than normal left ventricular contractile function (NYHA class II-IV). In 2023, coverage was expanded to first-line therapy for treating patients with chronic heart failure with a left ventricular ejection fraction of 40 percent or less.
"Novartis Korea will continue to do its utmost to address the unmet need for treatment of heart failure patients with ejection fraction rate exceeding 40 percent in Korea, as well as heart failure with reduced left ventricular ejection fraction, and to make Entresto more accessible," said Cho Yeon-jin, executive vice president of Cardiovascular Business Division at Novartis Korea.