Reviwer : Dr. Muhammet Dural

Name of the Study : LCZ696 in Advanced Heart Failure - LIFE

Published in Congress : ACC 2021

Full Text Link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286640/pdf/main.pdf

Background : It may not always be possible to apply guideline-directed therapy optimally in patients with advanced symptomatic low ejection fraction heart failure (HFrEF). In these patients, symptomatic hypotension and/or deterioration in renal function may develop earlier, which may lead to discontinuation or dose reduction of some drugs. In PARADIGM-HF study, sacubitril/valsartan (S/V) was shown to provide a significant reduction in mortality and hospitalization compared to enalapril. However, only <1% of patients in this study had NYHA class 4 symptoms.

Objective :  In LIFE study, it was aimed to evaluate the efficacy and safety of S/V in patients with advanced HFrEF by comparing them with patients receiving valsartan.

Method : Patients who were NYHA class 4 symptomatic for the past three months, had received guideline-directed therapy for ≥3 months and/or were intolerant to treatment, had a left ventricular ejection fraction of ≤35%, and had a B-type natriuretic peptide (BNP) ≥250 pg/ml or N-terminal pro-BNP (NT-proBNP) ≥800 pg/ml were enrolled to the study. Patients were randomized 1:1 fashion to either S/V (n = 167) and valsartan (n = 168).

Results : The rate of change in NT-proBNP, which was the primary endpoint of the study, was similar in the S/V and valsartan groups (p = 0.45). In addition, there was no significant difference between the two groups in cardiovascular death and hospitalization for heart failure (p = 0.20).

Conclusion : S/V did not provide significant reductions in NT-proBNP and clinical outcomes in patients with advanced symptomatic HFrEF.

Interpretation : S/V has been shown to provide significant improvement in clinical outcomes in patients with HFrEF. However, there was insufficient data in patients with advanced HFrEF. In LIFE trial, patients with advanced HFrEF were included in the study. S/V does not appear to be superior to valsartan in this patient group. Therefore, when starting S/V in these patients, additional comorbidities and hemodynamic parameters of the patient should be examined in detail and treatment should be individualized as much as possible.