Real-world comparative effectiveness of sacubitril/valsartan versus RAS inhibition alone in patients with de novo heart failure

Aims: Large-scale, real-world data on early initiation of sacubitril/valsartan in patients newly diagnosed (de novo) with HF with reduced ejection fraction (HFrEF) are limited. We examined the effectiveness of sacubitril/valsartan versus angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) on all-cause and cause-specific hospitalizations among patients with de novo HFrEF from the Optum® dataset in the United States. Methods: This retrospective cohort study included adult patients with de novo HFrEF (diagnosed ≤30 days) with left ventricular ejection fraction (LVEF) ≤40% who were first prescribed with sacubitril/valsartan or ACEi/ARB from 1 January 2016 to 31 March 2020. The primary endpoint (all-cause hospitalization) and secondary endpoints were analysed in propensity score-matched cohorts. Results: A cohort of 3290 patients with de novo HFrEF who were prescribed with sacubitril/valsartan and a propensity-matched cohort of 6580 patients who were prescribed with ACEi/ARB were analysed. Overall, the mean (SD) age of patients was 63 (14) years, 34% were women, and baseline characteristics were balanced across treatment groups. Hypertension (67%), diabetes (33%) and chronic kidney disease (28%) were highly prevalent comorbidities. Patients in the sacubitril/valsartan cohort when compared with the ACEi/ARB cohort had lower annual rates of all-cause hospitalizations [incidence rate ratio (IRR): 0.81, 95% confidence interval (CI): 0.75–0.89, P < 0.001], cardiovascular (CV) hospitalizations (IRR: 0.80, 95% CI: 0.73–0.87, P < 0.001) and HF hospitalizations (IRR: 0.86, 95% CI: 0.78–0.95, P = 0.002). Conclusions: Among patients with de novo HFrEF, sacubitril/valsartan (compared with that of ACEi/ARB) was associated with fewer all-cause, CV and HF hospitalizations. These findings are consistent with clinical trial evidence suggesting potential benefits of early initiation of sacubitril/valsartan in patients with HFrEF, including those soon after diagnosis.