Evaluating the safety and tolerability of inpatient sacubitril/valsartan initiation in a community hospital

Abstract

Background: Sacubitril/valsartan has been incorporated into guidelines based on the results of the PARADIGM-HF trial, which demonstrated reduced mortality in stable patients with heart failure with reduced ejection fraction (HFrEF). Sacubitril/valsartan is recommended in addition to other HF therapies in place of an angiotensin-converting-enzyme inhibitor or angiotensin-receptor-blocker. Objectives: To evaluate the safety and tolerability of sacubitril/valsartan initiation in a community hospital. Design/methods: This single-center, retrospective review evaluated patients that received ≥24 hours of sacubitril/valsartan therapy August 2015-March 2018. The primary outcome included the incidence of hypotensive events during hospitalization. Secondary outcomes included: incidence of inpatient acute kidney injury (AKI) and hyperkalemia, rates of inpatient discontinuation, and change in ejection fraction (EF) ≥30 days after initiation. Results: Of the 59 patients included, 21 (35.6%) experienced a hypotensive event. A total of 6 patients (10.2%) discontinued therapy while inpatient, which was more likely in patients that developed AKI (n = 3; p = 0.005) or those who experienced a hypotensive event (n = 5; p = 0.018). There was a significant difference in mean EF from baseline to ≥ 30 days postinitiation (24.8% vs. 33.2%; p = 0.018). Conclusion: Careful patient selection and monitoring for hypotension, AKI, and hyperkalemia can help increase successful outcomes and improve patient safety.

Inpatient Initiation of Sacubitril/Valsartan

“…3,10 Retrospective Data Inpatient initiation of sacubitril/valsartan has been described in 3 retrospective analyses of real-world data (Table 1). [13][14][15] Peppin et al 13 conducted a single-center retrospective review assessing the safety and tolerability of inpatient sacubitril/ valsartan initiation by determining adverse event (hypotension, acute kidney injury [AKI], and hyperkalemia) and drug discontinuation rates during hospitalization. The cohort included 59 patients, and the mean age was 69.4 years; 38 (64.4%) patients were male, 53 (89.8%) were Caucasian, and 41 (69.5%) were NYHA class II or III.…”

“…These 3 studies suggest that tolerability of sacubitril/ valsartan initiated in a real-world setting is similar to that in a randomized controlled setting because drug discontinuation rate was reported as 10.2% to 20.3%, which is in line with the discontinuation rate in the randomized trials PARADIGM-HF (17.8%), PIONEER-HF (19.6%), and TRANSITION (12.9%). 3,10,[12][13][14][15] However, it is important to note that these are small retrospective studies, which may not have accurately captured all adverse events and reasons for discontinuation. These data support careful monitoring of blood pressure and renal function as well as cost assessment of sacubitril/valsartan because these factors may affect patient tolerability and adherence.…”

“…4,10,17 Inpatient initiation has been described in the literature and appears to have a similar rate of adverse events to outpatient initiation, regardless of admitting diagnosis. [13][14][15] The most commonly reported adverse effect is hypotension, which can be most closely monitored in an inpatient setting. Other important considerations that can be closely assessed while hospitalized are renal function and patient affordability.…”

“…It is worth noting the relatively high continuation rate (~75% to 90%) postdischarge among patients who tolerate sacubitril/valsartan in an inpatient setting. 10,[13][14][15] Therefore, the close monitoring that occurs during hospitalization creates an ideal opportunity for sacubitril/valsartan initiation.…”

“…10 It is important to note that, in the summarized studies, lower doses were frequently initiated in hospitalized patients, including starting at half of the lowest-dose tablet (12/13 mg twice daily). 10,[13][14][15] In these studies, hypotensive events were still reported in up to 35.6% of patients, so it may be appropriate to start at low doses and titrate cautiously, taking patient-specific factors such as renal function and concomitant medications into account. 13 Because the tablets can be halved, initiating 12/13 mg twice daily is possible and could improve initial tolerance.…”