Safety and Tolerability of Sacubitril/Valsartan Initiation in Inpatient Versus Outpatient Setting: A Retrospective Real World Study.

BACKGROUND

The Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event (TRANSITION) and PIONEER-HF trials have shown that sacubitril/valsartan can be initiated early and safely in patients with heart failure with reduced ejection fraction (HFrEF) shortly after an acute heart failure episode during hospitalisation. However, it is unclear whether the results can be translated to Asian populations. Hence, this real-world study was designed with the aim of comparing the safety and tolerability of sacubitril/valsartan initiation in an inpatient versus outpatient setting.

METHODS

A retrospective review for all patients initiated with sacubitril/valsartan from 1 November 2015 to 30 September 2018 was conducted in a tertiary health care institution in Singapore. Patients with HFrEF and aged ≥21 years were included. Incidence of adverse drug reactions (ADRs) and discontinuation rate of sacubitril/valsartan were compared between initiation of sacubitril/valsartan in inpatient and outpatient settings. Reasons for discontinuation were investigated. Subgroup analysis was performed. Cox regression was used to analyse the primary outcomes.

RESULTS

Of the 1,022 patients who were screened, 840 (289 inpatient group; 551 outpatient group) were included. The inpatient group experienced significantly higher ADRs (34.6% vs 22.7%; adjusted hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.68-3.10; p<0.01) and discontinuation rate (18.0% vs 10.3%; adjusted HR, 2.11; 95% CI, 1.37-3.26; p<0.01) than the outpatient group. The safety outcomes were consistent across all the subgroups.

CONCLUSIONS

Initiation of sacubitril/valsartan in an inpatient group was associated with higher ADRs and discontinuation rate as compared with an outpatient group in an Asian population. However, given that the majority of patients in the inpatient cohort could tolerate sacubitril/valsartan, it would still be feasible to initiate this drug with close monitoring. Further randomised clinical trials in Asian populations are required to confirm this finding.