Usefulness of a titration algorithm for de novo users of sacubitril/valsartan in a tertiary centre heart failure clinic

Abstract

Background: A reduction in the rate of death and hospitalisations in patients with heart failure (HF) with reduced ejection fraction receiving sacubitril/valsartan compared to enalapril was demonstrated in the PARADIGM-HF study. However, tolerability when initiating and optimising sacubitril/valsartan treatment in real clinical practice is unknown. Methods: We performed a prospective cohort study of clinical and biochemical parameters of the first 100 patients receiving sacubitril/valsartan in a tertiary HF clinic. Patients had titration of the molecule guided by an algorithm developed by pharmacists and cardiologists in the clinic. The objective was to evaluate the proportion of patients reaching the maximal dosage, the time to reach maximal dosage, and the rate of adverse events, as well as the required modification of other HF therapy during the sacubitril/valsartan titration. Results: Forty-six per cent of patients reached the sacubitril/ valsartan maximal dose of 97/103 mg (200 mg) twice daily and 73% received at least 49/51 mg (100 mg) twice daily. Mean titration time was 30 ± 9 days. Symptomatic hypotension, renal dysfunction (increase in creatinine level > 30%) and hyperkalaemia (potassium level > 5.5 mmol/l) occurred in nine, four and 2% of patients, respectively. Background HF pharmacological treatment remained stable during the sacubitril/valsartan titration but daily dosage of furosemide was reduced by 13% (p = 0.0005). Conclusions: This algorithm is a safe and easy-to-use tool in daily clinical practice for the introduction and titration of sacubitril/valsartan. Almost half of the patients reached the maximal dose, with a tolerability profile in line with the original study.

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

“…The clinical importance of these data is that they reinforce the positive observations from the clinical trial data, and the emerging real world data, and indicate that the majority of the cohort of community patients can tolerate the agent and benefit from the compound, in terms of either a reduction in NT‐proBNP or an improvement in LVEF. More importantly, these data support the importance of achieving maximum dose and link this to a reduction in diuretic use, establishing clinical volume assessment as a critical feature in using this agent.…”

“…As observed from the PARADIGM sub-analysis by Jhund PS et al, when the authors assessed the efficacy and safety of sacubitril-valsartan by age, they found that the superiority of sacubitril-valsartan over enalapril persisted across all age groups including the elderly, though the same efficacy gap decreased slightly in the older population. 34 The clinical importance of these data is that they reinforce the positive observations from the clinical trial data, 1,33,35 and the emerging real world data, 14,15,17 and indicate that the majority of the cohort of community patients can tolerate the agent and benefit from the compound, in terms of either a reduction in NT-proBNP or an improvement in LVEF. More importantly, these data support the importance of achieving maximum dose and link this to a reduction in diuretic use, establishing clinical volume assessment as a critical feature in using this agent.…”

“…Some studies have reported rates as low as 17%, and the majority of studies achieved the maximum dose in less than 50% of individuals. 11,15,16 Given that emerging data indicate that the higher doses are associated with superior clinical response, 11,18 close analyses of the impediments to dose titration in the community are warranted in order to provide guidance on how best this agent in this setting. Our data demonstrate that the clinical trial dose of sacubitril-valsartan can be achieved in a significant proportion of the population.…”

“…Notably however, achievement of TD of sacubitril‐valsartan appears to be more of a challenge in the community. Some studies have reported rates as low as 17%, and the majority of studies achieved the maximum dose in less than 50% of individuals . Given that emerging data indicate that the higher doses are associated with superior clinical response, close analyses of the impediments to dose titration in the community are warranted in order to provide guidance on how best this agent in this setting.…”

“…In the main, observations have been in line with what has been reported in the clinical trial data. [10][11][12][13] However, there has been a lower rate of achievement of the target dose (TD), with the majority of studies reaching TD in less than 50% the patients, 14,15 including a large cohort in Germany. 16 To our knowledge, only one study to date had reported success in titration to TD in greater than 50% of the cases.…”