Physicians' Academy for Cardiovascular Education

ARNI not superior to ARB for advanced HF

News - May 18, 2021

Sacubitril/Valsartan (LCZ696) In Patients With Advanced Heart Failure And Reduced Ejection Fraction: Results Of The LIFE Trial

Presented at ACC.21 by Prof. Douglas Mann, MD (St. Louis, MO, USA)

Introduction and methods

PARADIGM-HF showed that sacubitril/valsartan reduced morbidity and mortality in patients with chronic HFrEF compared to enalapril. However, less than 1% of patients in PARADIGM-HF had NYHA class IV HF. The LIFE trial investigated whether sacubitril/valsartan is superior to valsartan with respect to lowering NT-proBNP levels in patients with advanced HFrEF.

LIFE was a prospective, multicenter, double-blind, active-comparator trial in 335 patients with advanced HF. Key entry criteria included NYHA class IV symptoms in the previous 3 months, receiving GDMT for HF for ≥3 months or intolerant to GDMT, LVEF≤35%, BNP≥250 pg/mL or NT-proBNP≥800 pg/mL, SBP>90 mmHg and at least 1 additional objective finding of advanced HF. Patients were randomized 1:1 to receive either sacubitril/valsartan (n=167) or valsartan (n=168) during a 24-week double-blind treatment period. The primary endpoint was area under the curve (AUC) for the proportional change in NT-proBNP levels from baseline through 24 weeks. The secondary efficacy endpoint was days alive, out of hospital and free from HF events. Secondary tolerability endpoints included drug tolerability, hypotension, worsening renal function and hyperkalemia.

Main results


Sacubitril/valsartan was not superior to valsartan with respect to changing NT-proBNP levels in patients with advanced HF. Sacubitril/valsartan did not improve the secondary endpoint of days alive, out of hospital and free from HF events and did not decrease CV death or HF hospitalization compared to valsartan. There was a higher number of patients experiencing non-life threatening hyperkalemia in sacubitril/valsartan arm compared to the valsartan arm.


The discussant Gurusher Panjrath, MD (Washington, DC, USA) found the results surprising. He thinks that we need more insight about the phenotype of patients with advanced HF in this trial. A close look at the enrolment criteria is necessary to understand who had truly advanced HF vs. who had decompensated HF.

-Our coverage of ACC.21 is based on the information provided during the congress –

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