Sacubitril/valsartan vs. angiotensin receptor inhibition in heart failure: a real-world study in Taiwan

Abstract

Aims: This study aimed to compare the efficacy of angiotensin receptor-neprilysin inhibitor (ARNI) therapy with angiotensin receptor blocker (ARB) therapy for cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction.

Methods and results: Data were obtained from the Chang Gung Research Database. The cohort entry date of the ARB group was assigned as that of the ARNI group to avoid immortal time bias. Additionally, 1:1 propensity score matching based on age, sex, and baseline left ventricular ejection fraction was conducted. The expectation-maximization imputation method with inverse probability of treatment weighting was used to compare outcomes between the two groups. The primary outcome was a composite of cardiovascular death and hospitalization for worsening HF. Patients who received ARNI therapy had a significantly lower risk of the primary composite outcome occurring than patients who received ARBs (hazard ratio, 0.74; 95% confidence interval, 0.57-0.96). The reduction of hospitalization for worsening HF contributed most to the primary outcome benefits. In addition to the primary outcome, the ARNI group had a significantly lower risk of non-fatal myocardial infarction. The improvement of ejection fraction was not significantly different between the groups. The medication doses of ARNI were lower than in clinical trials.

Conclusions: In patients with HF with reduced ejection fraction, sacubitril/valsartan was superior to ARB therapy in reducing the occurrence of the primary outcome endpoint of hospitalization for worsening HF and cardiovascular death.

Keywords: Angiotensin receptor blockers; Heart failure; Sacubitril/valsartan (LCZ696).

FIGURE 1

Flow chart for patient inclusion. Patients with heart failure with reduced ejection fraction and prescribed with angiotensin receptor–neprilysin inhibitors (ARNIs) or angiotensin receptor blockers (ARBs, including valsartan, losartan, and candesartan) were included. After the assignment of the cohort entry date and matching by sex, age, and left ventricular ejection fraction (LVEF), 539 patients were included in each group. Patients without follow‐up data were excluded, and the remaining patients with complete follow‐up data were included in the clinical outcome analyses. Among the patients, only 331 ARNI users and 315 ARB users had echocardiographic follow‐up at 12 months and were included in the analyses of the echocardiographic results.

FIGURE 2

Inverse probability of treatment weighting‐adjusted cumulative event rate of the primary composite endpoint (heart failure hospitalization or cardiovascular death) during the 1 year follow‐up between the angiotensin receptor–neprilysin inhibitor (ARNI) group and the angiotensin receptor blocker (ARB) group in the expectation–maximization‐imputed cohort. The ARNI group had a lower risk of a negative outcome than did the ARB group. CI, confidence interval.

FIGURE 3

Unadjusted cumulative event rate of primary composite endpoints during the 1 year follow‐up in the 431 angiotensin receptor–neprilysin inhibitor (ARNI) users stratified by the ability to tolerate higher doses (≥200 mg/day). The patients who could not tolerate higher doses (<200 mg/day) of ARNI therapy had a slightly less favourable primary composite endpoint outcome. CI, confidence interval.