Impact of systolic blood pressure on the safety and tolerability of initiating and up‐titrating sacubitril/valsartan in patients with heart failure and reduced ejection fraction: insights from the TITRATION study

Abstract

The majority of patients (>80%) with SBP of ≥100 mmHg achieved and maintained the target dose of sacubitril/valsartan if the treatment was titrated gradually. These findings suggest that low SBP should not prevent clinicians from considering the initiation of sacubitril/valsartan.

Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study

“…In a post-hoc analysis of TITRATION, > 80% of patients with SBP ≥ 100 mmHg achieved and maintained the target dose of sacubitril/valsartan if the treatment was titrated gradually. 22 We observed that ACEI/ARB-naïve patients were similar to patients on an ACEI or ARB able to initiate, up-titrate and maintain sacubitril/valsartan. These findings address a key question that had remained unanswered in the PARADIGM-HF study.…”

“…Similar to ACEI or ARB management, slow up‐titration to target dose in the highly vulnerable post‐ADHF phase is recommended. In a post‐hoc analysis of TITRATION, > 80% of patients with SBP ≥ 100 mmHg achieved and maintained the target dose of sacubitril/valsartan if the treatment was titrated gradually . We observed that ACEI/ARB‐naïve patients were similar to patients on an ACEI or ARB able to initiate, up‐titrate and maintain sacubitril/valsartan.…”

Sacubitril/valsartan eligibility and outcomes in the ESC‐EORP‐HFA Heart Failure Long‐Term Registry: bridging between European Medicines Agency/Food and Drug Administration label, the PARADIGM‐HF trial, ESC guidelines, and real world

“…Furthermore, there was a greater risk of symptomatic hypotension in the LCZ696 arm than in the enalapril arm . Although LCZ696 dose titration to the target dose seemed to be feasible in the majority (> 80%) of patients with systolic blood pressure > 100 mmHg enrolled in another randomized study, more than 90% of the study participants had tolerated an ACEi/ARB prior to screening, whereas an open‐label 5‐day run‐in phase of LCZ696 50 mg twice daily was also included. Another randomized trial assessing the feasibility and safety of pre‐discharge vs. post‐discharge initiation of LCZ696 in HFrEF patients hospitalized for HF decompensation was recently presented .…”

August 2019 at a glance: arrhythmogenic cardiomyopathy, biomarkers of inflammation, insulin treatment, initiation of sacubitril/valsartan, and pharmacy‐based intervention to increase medication adherence

“…Unmet needs regard implementation of this drug. Hypotension, above all if symptomatic, remains a major limitation, and a strategy of slow dose titration may allow better tolerability and adherence to treatment . In‐hospital initiation may also allow treatment implementation.…”

“…Hypotension, above all if symptomatic, remains a major limitation, and a strategy of slow dose titration may allow better tolerability and adherence to treatment. 16 In-hospital initiation may also allow treatment implementation. Sacubitril/valsartan initiation in an in-hospital setting vs. an outpatient setting, such as in PARADIGM-HF, was compared in the Comparison of Pre-and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event (TRANSITION) study.…”