LIFE (sacubitril/valsartan)
Trial question
What is the effect of sacubitril/valsartan in patients with chronic advanced HFrEF?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
27.0% female
73.0% male
N = 335
335 patients (90 female, 245 male).
Inclusion criteria: patients with chronic advanced HFrEF.
Key exclusion criteria: currently taking sacubitril/valsartan; hypersensitivity or intolerance to sacubitril/valsartan; eGFR < 20 mL/min/1.73 m²; symptomatic hypotension or SBP < 90 mmHg; serum potassium > 5.5 mmol/L; severe liver dysfunction.
Interventions
N=167 sacubitril/valsartan (target dose 200 mg BID in addition to recommended therapy).
N=168 valsartan (target dose 160 mg BID in addition to recommended therapy).
Primary outcome
Median N-terminal pro-brain natriuretic peptide area under curve through 24 weeks of therapy
1.08
1.19
1.2
0.9
0.6
0.3
0.0
Sacubitril/valsartan
Valsartan
No significant
difference ↔
No significant difference in median NT-proBNP AUC through 24 weeks of therapy (1.08 vs. 1.19; RR 0.95, 95% CI 0.84 to 1.08).
Secondary outcomes
No significant difference in median days alive, out of hospital, and free from HF events (147 days vs. 157 days; AD -11.2 days, 95% CI -26.4 to 4).
No significant difference in CV death or HF hospitalization (29% vs. 22%; HR 1.32, 95% CI 0.86 to 2.03).
No significant difference in all-cause mortality (8% vs. 5%; HR 1.63, 95% CI 0.68 to 3.94).
Safety outcomes
No significant difference in symptomatic hypotension or worsening kidney function.
Significant difference in hyperkalemia (17% vs. 9%).
Conclusion
In patients with chronic advanced HFrEF, sacubitril/valsartan was not superior to valsartan with respect to median NT-proBNP AUC through 24 weeks of therapy.
Reference
Douglas L Mann, Michael M Givertz, Justin M Vader et al. Effect of Treatment With Sacubitril / Valsartan in Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. JAMA Cardiol. 2022 Jan 1;7(1):17-25.
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