Titration and Tolerability of Sacubitril/Valsartan for Patients With Heart Failure in Clinical Practice

Abstract

Little is known about the dosing and tolerability of sacubitril/valsartan (LCZ696; Entresto, Quebec, Canada) in a nonclinical trial population. This study was conducted to evaluate the use and tolerability of sacubitril/valsartan in patients followed at a multidisciplinary heart failure (HF) clinic. We performed a retrospective chart review of 126 patients with HF, initiated on sacubitril/valsartan, and seen at a specialty HF clinic between August 1, 2015, and August 1, 2017. We defined the target dose of sacubitril/valsartan as 200 mg twice a day. At baseline, median age was 67 years, 77% were men, median ejection fraction was 29%, and 86.5% of patients had symptoms of New York Heart Association class ≥II. Within 6 months of being transitioned onto sacubitril/valsartan therapy, 27.2% achieved the target dose of 200 mg twice a day, 40.8% achieved the target dose of 100 mg twice a day, and 32.0% achieved the target dose of 50 mg twice a day. The main reasons for not achieving target dose within 6 months included slower uptitration of therapy than in the trial (n = 41, 54.7%), a decrease in systolic blood pressure (n = 19, 25.3%), not completing blood work (n = 3, 4%), and patient noncompliance (n = 3, 4%). Overall, achievement of sacubitril/valsartan target doses was modest in a tertiary HF clinic, limited by various factors such as side effects and patients' medication noncompliance. Implementation of patient and clinician support pathways may improve uptake, uptitration, and maintenance of evidence-based doses in clinical practice.

Introduction of sacubitril/valsartan in primary care follow‐up of heart failure: a prospective observational study (THESEUS)

“…The low rate of sac/val target dose achievement is in line with previous reports from CHF outpatient clinics 17,18 . Nevertheless, NYHA classification and well‐being improved for both ‘Achievers' and ‘Non‐Achievers', suggesting that patients had improved well‐being and clinical stability compared with their pretrial experience regardless of sac/val target dose achievement or maintenance.…”

“…The low rate of sac/val target dose achievement is in line with previous reports from CHF outpatient clinics. 17,18 Nevertheless, NYHA classification and well-being improved for both 'Achievers' and 'Non-Achievers', suggesting that patients had improved well-being and clinical stability compared with their pretrial experience regardless of sac/val target dose achievement or maintenance. In addition, when comparing with the 6 months period preceding the trial, less healthcare utilization was observed with sac/val treatment on both 'Achievers' and 'Non-Acievers', which is in accordance with a reduced number of unplanned rehospitalizations found in PARADIGM-HF.…”

Heart failure epidemiology and treatment in primary care: a retrospective cross‐sectional study

“…While sex distribution of these patients was in accordance with previous studies 35,36 and can at least partly be explained by the lower proportion of HFrEF in women, 12,37 age was again considerably increased in this patient group. 35,36 Moreover, we found that sacubitril/valsartan patients more often had diabetes mellitus and a higher weight than the other HF patients. This might be an indication for multimorbid patients having a higher chance of suffering from severe HF, consequently rendering them eligible for sacubitril/valsartan treatment.…”

“…Similarly, the low blood pressure observed for sacubitril/valsartan‐treated patients (115/68 mmHg) could be a combination of the strong blood pressure‐lowering effects of sacubitril/valsartan and the severity of HF leading to sacubitril/valsartan prescription, which is often accompanied by low blood pressure. Lastly, the observed target dose achievement for sacubitril/valsartan (28.6%) was similar to the one observed in a Canadian HF clinic (27.2%) 36 but slightly lower than in a study conducted in Swiss primary care (36.5%) 39 . However, it must be considered that our study was cross‐sectional, meaning that some patients might still be in the process of up‐titration.…”

Improvement in quality of life with sacubitril/ /valsartan in cardiac resynchronization non-responders: The RESINA (RESynchronization plus an Inhibitor of Neprilysin/Angiotensin) registry

“…In the PARADIGM-HF trial [6], 42% had a reduced dose, and in the PIONEER trial [26] only 55% of the patients had the highest dose. In a real-life study by Du et al [27], at the 6month follow-up visit 27% of patients had the highest dose, 41% the mean dose and 32% the lowest dose. In elderly patients, dose reduction or discontinuation of the drug has been associated with hypotension and/or onset of renal failure.…”