Determinants of maximal dose titration of sacubitril/valsartan in clinical practice

Background: Little information is available about the tolerability of uptitration to the maximal dose of sacubitril/valsartan and the predictors and clinical correlates of achieving such a dose. Methods: All consecutive heart failure patients with reduced ejection fraction (HFrEF) who received sacubitril/valsartan for a class-IB indication in a tertiary heart failure clinic were retrospectively analysed. Predictors of maximal uptitration including associated changes in clinical parameters were assessed in patients with at least 1 follow-up. Results: A total of 401 HFrEF-patients received sacubitril/valsartan. Uptitration was possible in 41% and up to 32% of patients tolerated the maximal dose of sacubitril/valsartan. Younger age (HR = 0.862; CI = 0.751-0.989), higher systolic-blood-pressure (HR = 1.077; CI = 1.014-1.137), lower serum creatinine (HR = 0.064; CI = 0.005-0.822), and higher previous dose of renin-angiotensin-system-inhibitors (RASi [HR = 1.065; CI = 1.016-1.115]) independently predicted a higher odds of tolerating a maximal dose of sacubitril/valsartan. Patients who were seen more frequently in a structured heart failure clinic were also more likely to receive a maximal dose (p = .038). Patient assigned to the maximal dose, were more often able to reduce their loop diuretic dose (p = .001) and more often had an increase in serum creatinine (p = .011), without a higher risk for hyperkalemia (p = .524). An improvement in New York Heart Association class and the rate of heart failure hospitalisations was observed in all patients, independent of the sacubitril/valsartan dose. Conclusion: Uptitration to the maximal dose of sacubitril/valsartan is possible in up to 32% of real-world HFrEF-patients in our cohort, which relates to both patient characteristics' as well as heart failure care-related factors.