Clinical outcomes according to the average daily dose of sacubitril/valsartan: a nationwide longitudinal cohort study.

Abstract

Aims: A minority of patients with heart failure (HF) are prescribed the maximal dose of the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan. We investigated the effectiveness of submaximal doses of sacubitril/valsartan in a real-world cohort.

Methods and results: Patients with HF with reduced ejection fraction prescribed sacubitril/valsartan for ≥ 180 days between 2016 and 2020 were included from a nationwide database, and categorized into tertiles based on the average daily sacubitril/valsartan dosage. Baseline characteristics were balanced using inverse probability of treatment weighting with propensity scores. The primary outcome was a composite of HF hospitalization and all-cause mortality. The study included 3,953 patients (age 62.6 ± 12.4 years, 73.0% men). Patients on lower sacubitril/valsartan doses were older, more likely to be women, and had more comorbidities, with lower blood pressure, reduced kidney function, and lower body mass index; however, baseline characteristics were well balanced across the groups after weighting. During a mean follow-up of 2.0 ± 0.7 years, there were 808 events (20.4%). The risk of the primary outcome in the middle (HR 0.93, 95% CI 0.78-1.10) and the highest dosage tertiles (HR 0.88, 95% CI 0.74-1.06) did not significantly differ compared with the lowest dosage tertile (p-value = 0.384). Regarding individual outcomes, there was no significant difference in HF hospitalization; however, there was a trend toward lower mortality with higher sacubitril/valsartan dose (p-value = 0.047).

Conclusions: No significant difference was observed in the composite risk of HF hospitalization and all-cause mortality across different sacubitril/valsartan dosage groups. This suggests that the benefits of sacubitril/valsartan treatment may not necessarily be dose-dependent.