Physicians' Academy for Cardiovascular Education

Down-titration of diuretics predicts achievement of target dose of ARNI in real-world HFrEF patients

Sacubitril-Valsartan in a routine community population: attention to volume status critical to achieving target dose

Literature - Pharithi RB, Ferre-Vallverdu M, Maisel AS et al., - ESC Heart Fail. 2020. doi: 10.1002/ehf2.12547.

Introduction and methods

The PARADIGM-HF trial demonstrated that sacubitril-valsartan reduced mortality and HF hospitalization in patients with HFrEF [1]. In addition, sacubitril-valsartan was found to be safe and effective when started during acute decompensated HF admission [2]. Sacubitril-valsartan is licensed for use in well-defined circumstances [3,4]. Real-world HFrEF patients are likely to be older, frailer and have an increased burden of comorbidities compared to clinical trial populations [5-7]. Furthermore, the majority of real-world studies on sacubitril-valsartan reported that the target dose was achieved in less than 50% of patients [8-10]. Achievement of the maximum dose influences outcomes [11,12]. There is therefore a need to better understand how real-world patients respond to sacubitril-valsartan with special focus on the tolerability, achieved dose and response patterns.

This single-center, retrospective, observational study examined the effect of sacubitril-valsartan in HFrEF (LVEF ≤35%) patients treated in outpatient clinics. 297 Stable HFrEF patients who were on maximally tolerated doses of ACEi/ARB therapy switched to sacubitril-valsartan. The median age was 70.0 years (61.9,76.2), 75% were male patients, and the median LVEF was 28% (23.7%,33.0%). Median follow-up in patients who tolerated sacubitril-valsartan was 519 days (281-738 days).

The primary endpoints were tolerability of sacubitril-valsartan and achievement of the target dose. Secondary endpoints were I) a reduction in NT-proBNP ≥ 30%, II) an increase in LVEF of ≥ 5% and III) an alteration of diuretic need.

Main results


This single-center, retrospective, observational analysis of stable HFrEF patients who switched from ACEi/ARB therapy to sacubitril-valsartan, showed that sacubitril-valsartan was well tolerated in a routine community population. Target dose was achieved in the majority of the population. Reduction in diuretic dose was the strongest independent predictor of achieving the target dose of sacubitril-valsartan. These findings underline the importance of careful clinical assessment of volume status during the titration period.


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