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

Abstract

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.

Keywords:

• Heart failure
• sacubitril/valsartan
• dosing
• outcome
• guidelines
• real world evidence

Disclosure statement

Pieter Martens has received consultancy fees from Novartis, Vifor Pharma, Boehringer Ingelheim, and AstraZeneca. All authors have nothing relevant to disclose relating this manuscript.

Additional information

Funding

Pieter Martens is supported by a doctoral fellowship by the Research Foundation—Flanders (FWO, grant-number: 1127917N). Pieter Martens and Wilfried Mullens are researchers for the Limburg Clinical Research Centre (LCRC) UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk (LSM), Hasselt University, Ziekenhuis Oost-Limburg, and Jessa Hospital.