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.

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