Sacubitril/Valsartan Associates With Favorable 1-Year Outcomes in HFrEF

Sacubitril/valsartan therapy improves clinical outcomes at 12 months in patients with heart failure with reduced ejection fraction, regardless of age group.

Among patients with heart failure with reduced ejection fraction (HFrEF), sacubitril/valsartan improves prognostic biomarkers and health status at 12 months, regardless of age group. These findings were published in JACC: Heart Failure.

The PROVE-HF (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes; Identifier: NCT02887183) study was a 52-week, multicenter, open-label, single-arm study. Patients (N=794) with HFrEF initiated sacubitril/valsartan and titrated to a target dose of 97/103 mg twice daily. For this post-hoc analysis, 1-year outcomes were evaluated.

The study population comprised 28.5% women who were had a mean age of 65.1±12.4 years. Stratified by age, 369 patients were aged younger than 65 years, 237 were aged 65 to 74 years, and 188 were aged 75 years or older. More of the older patients were White, had more comorbidities, lower body mass index, and fewer were previously hospitalized for HF compared with younger patients.

The target sacubitril/valsartan dose was achieved by 65% of patients. Stratified by age, more of the youngest (60.9%) and intermediate aged (65%) cohorts achieved the target dose compared with the oldest cohort (55.3%; P =.003). The most common reasons for failure to reach the target dose were unrelated tolerability (19.8%), other (8.1%), and symptomatic hypotension (5.0%).

Sac/Val was well tolerated and resulted in significant improvements in prognostic biomarkers and measures of cardiac remodeling and health status from baseline to month 12 across age categories.

After sacubitril/valsartan initiation, N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T, and soluble suppressor of tumorigenicity-2 levels decreased significantly.

Stratified by age group, NT-proBNP was reduced less among the oldest group (geometric mean [GM], -30.5%) compared with the intermediate aged (GM, -40.2%) or youngest (GM, -45.6%) cohorts (P =.02). Similarly, the improvement in Kansas City Cardiomyopathy Questionnaire-23 scores following sacubitril/valsartan initiation was more subtle among the oldest group (mean, +6.0 points) compared with the intermediate aged (mean, +11.4 points) or youngest (mean, +11.8 points) cohorts (P =.03).

The improvements in most reverse cardiac remodeling signatures were similar among the age groups, with a 9.2% to 9.8% increase in left ventricular (LV) ejection fraction, 12.0 to 12.9 ml/m2 decrease in LV end-diastolic volume index, 15.2 to15.7 ml/m2 decrease in LV end-systolic volume index, and 7.1 to 7.9 ml/m2 decrease in left atrial volume index. For E/e’, the youngest group improved from 12.9 at baseline to 10.6 at 12 months, the intermediate aged group improved from 13.5 to 12.5, and the oldest group improved from 14.1 to 13.5. At 12 months, the youngest group had significantly lower E/e’ than the oldest group (P <.001).

The safety profile did not differ significantly on the basis of age, with 15.7% to 18.6% of patients reporting dizziness, 16.9% to 19.1% hypotension, 10% to17.7% hyperkalemia, 9% to 13.6% worsening renal function, and 0.5% to 0.8% angioedema.

The major limitation of this study is the lack of a comparator cohort.

“Sac/Val [sacubitril/valsartan] was well tolerated and resulted in significant improvements in prognostic biomarkers and measures of cardiac remodeling and health status from baseline to month 12 across age categories,” the study authors wrote.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Murphy SP, Ward JH, Piña IL, et al. Age differences in effects of sacubitril/valsartan on cardiac remodeling, biomarkers and health status. J Am Coll Cardiol HF. Published online September 07, 2022. doi:10.1016/j.jchf.2022.07.001