Internal medicine

Cardiology

Sacubitril, Valsartan

Sacubitril

Valsartan

Heart failure

Population

Medicine

Ejection fraction

Blood pressure

Environmental health

JAMA Cardiology

<h3>Importance</h3> The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population. <h3>Objective</h3> To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms. <h3>Design, Setting, and Participants</h3> A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk. <h3>Intervention</h3> Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy. <h3>Main Outcomes and Measures</h3> The area under the curve (AUC) for the ratio of N-terminal pro–brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy. <h3>Results</h3> Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08;<i>P</i> = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non–life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%];<i>P</i> = .04), there were no observed safety concerns. <h3>Conclusions and Relevance</h3> The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02816736

Effect of Treatment With Sacubitril/Valsartan in Patients With Advanced Heart Failure and Reduced Ejection Fraction