In HFrEF,
PARADIGM-HF: ENTRESTO® reduced 15-day heart failure readmissions vs enalapril
ENTRESTO demonstrated fewer 15-day heart failure readmissions in a post hoc analysis1
15-day heart failure readmissions
15-day heart failure readmissions
30-day heart failure readmissions
PARADIGM-HF: Readmission was defined as the second hospitalization within 30 days of the first hospitalization after initiation of study drug.1
†Vs enalapril.
‡Among patients hospitalized at least once for heart failure, patient characteristics were similar at baseline between treatment groups.
This was a post hoc analysis of heart failure readmissions following investigator-reported heart failure hospitalizations; investigator-reported events are vulnerable to misclassification
Patients were randomized to ENTRESTO or enalapril prior to index hospitalization; the apparent differences in readmission rate could be attributed to differences in the patients
The primary unit of subsequent analysis was hospitalizations rather than patients
15-day readmissions for heart failure is not a routinely examined time point in quality and clinical assessments, and such early time points may not reflect causality
8-week heart failure readmissions: prespecified exploratory end point
§PIONEER-HF: Readmission was defined as the first hospitalization after inpatient initiation of study drug.5
This was a prespecified exploratory end point; the study was powered for changes in NT-proBNP
Results should be interpreted with caution due to the short time frame and infrequency of events
¶Cardiac failure congestive and acute kidney injury were per investigator discretion on the Case Report Form.
For key safety outcomes, the ENTRESTO group and the enalapril group were generally comparable with regard to rates of worsening renal function, hyperkalemia, symptomatic hypotension, or angioedema5
Adverse event profile was comparable to that in the PARADIGM-HF trial3,5
No new safety signals were observed3,5
Safety data were collected for only 8 weeks, therefore adverse events that take longer to transpire may not have appeared in this study. Safety information should be interpreted in the context of prior trials with longer duration5
*In PARAGON-HF, defined as LVEF ≥45% with structural heart disease (LAE or LVH); median LVEF was 57%. LVEF is a variable measure and the normal range can vary.3
BOXED WARNING: FETAL TOXICITY
ENTRESTO is contraindicated in patients with hypersensitivity to any component...
ENTRESTO is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal.
LVEF is a variable measure, so use clinical judgment in deciding whom to treat.
Definitions
ACEi, angiotensin-converting enzyme inhibitor; ADHF, acute decompensated heart failure; ARB, angiotensin II receptor blocker; ARR, absolute risk reduction; BP, blood pressure; CI, confidence interval; HR, hazard ratio; IV, intravenous; KM, Kaplan–Meier; LVEF, left ventricular ejection fraction; NNT, number needed to treat; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; RRR, relative risk reduction.
References
1. Data on file. PARADIGM-HF and all-cause readmission analysis. Novartis Pharmaceuticals Corp; August 1, 2019.
2. Desai AS, Claggett BL, Packer M, et al; for the PARADIGM-HF Investigators. Influence of sacubitril/valsartan (LCZ696) on 30-day readmission after heart failure hospitalization. J Am Coll Cardiol. 2016;68(3):241-248.
3. ENTRESTO [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.
4. McMurray JJV, Packer M, Desai AS, et al; for the PARADIGM-HF Investigators and Committees. Angiotensin–neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. doi:10.1056/NEJMoa1409077
5. Velazquez EJ, Morrow DA, DeVore AD, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure [published correction appears in N Engl J Med. 2019;380(11):1090]. N Engl J Med. 2019;380(6):539-548. doi:10.1056/NEJMoa1812851