Risk Factors for Intolerance of Inpatient Sacubitril/Valsartan Initiation

Abstract

Background: Sacubitril/valsartan has been shown to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, initiation of sacubitril/valsartan has primarily been studied in stable, ambulatory patients with HFrEF. Objective: The objective of this study was to determine risk factors for intolerance to inpatient sacubitril/valsartan initiation. Methods: This was a retrospective, single-center study from August 1, 2015 through April 30, 2018. Patients were at least 18 years old and were newly initiated on sacubitril/valsartan during their hospitalization. Results: A total of 143 patients met inclusion criteria. Of these patients, 20.3% (n = 29) were intolerant to inpatient initiation of sacubitril/valsartan. The primary reason for intolerance was hypotension (n = 19, 65.5%). Patients with newly diagnosed heart failure were more likely to tolerate the initiation of sacubitril/valsartan (32.5% vs 10.3%; P = 0.03). No differences between groups were identified among other potential predictors for intolerance to sacubitril/valsartan, including systolic blood pressure, acutely decompensated heart failure, or serum creatinine. The most common adverse event was hypotension, which occurred in 26.6% (n = 38) of all patients. Conclusion: The majority of inpatients tolerated sacubitril/valsartan initiation. Larger, prospective, randomized controlled trials would be helpful in further determining ideal candidates for inpatient sacubitril/valsartan initiation.

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.…”

“…A second single-center, retrospective study evaluated hospitalized patients who were newly initiated on sacubitril/valsartan during admission. 14 The primary objective was to determine differences between patients who tolerated and those who discontinued the medication during hospitalization. The authors defined intolerance as being initiated on sacubitril/valsartan but discharged without therapy.…”

“…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.…”