ARNI Cuts 30-Day Readmission vs ACE-Inhibitor in Low-EF Heart Failure: PARADIGM-HF

Marlene Busko

July 20, 2016

BOSTON, MA — In a study of patients with heart failure and reduced ejection fraction (HFrEF), those treated with the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan (Entresto, Novartis) were less likely to be hospitalized within 30 days than those treated with the ACE inhibitor enalapril[1].

Dr Akshay S Desai (Brigham and Women's Hospital, Boston, MA) and colleagues reported these findings based on data from the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, in a study published online July 11, 2016 in the Journal of the American College of Cardiology.

"Reducing early readmissions after HF hospitalization represents an opportunity to simultaneously improve patient outcomes and reduce the fiscal burden of HF management for hospitals and payers," they write. The findings provide another reason to use "sacubitril/valsartan in preference to enalapril in patients with chronic, symptomatic HF and reduced ejection fraction."

Although the mechanisms of how neprilysin inhibition may prevent repeat hospitalization for HF remain to be determined, "these data further support the potential benefits of this approach on slowing the clinical progression of patients surviving with HF," according to the researchers.

In an accompanying editorial[2], Drs Robert J Mentz and Emily C O’Brien (Duke Clinical Research Institute, Durham, NC) caution that the findings may not be generalizable to all patients with HF, but for patients "with chronic HF with reduced ejection fraction able to tolerate the relatively high doses of enalapril and then sacubitril/valsartan . . . the posthospitalization period following clinical stabilization may be the ideal time to initiate the therapy" with this ARNI, they agree.

Seeking a Strategy to Lower Readmission for HF

Roughly one in four patients over age 65 who is hospitalized with HF and then discharged will be readmitted within 30 days, according to Desai and colleagues.

To try to improve this, since 2009, the US Centers for Medicare and Medicaid Services have publicly reported hospitals' rates of 30-day readmission for HF, and since 2010, hospitals with high readmission rates have had heavy financial penalties.

Recently, the PARADIGM-HF trial of 8399 patients with HFrEF showed that patients who received sacubitril/valsartan (200 mg twice daily) had a 20% lower rate of the primary composite end point of cardiovascular death or HF hospitalization than patients who received enalapril (10 mg twice daily).

To investigate whether treatment with sacubitril/valsartan might lower 30-day readmission to the hospital compared with enalapril, Desai and colleagues identified 1450 patients in the PARADIGM-HF trial who survived at least one HF hospitalization (675 patients in the sacubitril/valsartan arm and 775 patients in the enalapril arm).

There were 2383 investigator-reported 30-day HF hospitalizations in PARADIGM-HF: 45.2% in patients assigned to sacubitril/valsartan and 54.8% in patients assigned to enalapril.

The rate of 30-day hospital readmission for all causes was lower in the ARNI-treated group vs the enalapril-treated group (17.8% vs 21.0%).

Similarly, the rate of 30-day hospital readmissions for HF was lower in the ARNI-treated group vs the enalapril-treated group (9.7% vs 13.4%).

Risk of 30-Day Hospital Readmission, ARNI- vs Enalapril-Treated Group

Reason for 30-d hospital readmission Odds ratio (95% CI) P
All causes 0.74 (0.56–0.97) 0.031
HF 0.62 (0.45–0.87) 0.006

The findings were similar for 60-day hospital readmission and adjudicated HF readmission.

"Although the study results are encouraging, it is unknown whether similar results would be seen in those with less clinical stability and/or more advanced HF characterized by hypotension and renal dysfunction," Mentz and O'Brien caution, adding that these data do not apply to approximately 50% of the HF population with preserved ejection fraction.

Nevertheless, the findings suggests that "through care delivery that uses comprehensive discharge planning and patient education with appropriate initiation of evidence-based therapies and early postdischarge follow-up, it may be possible to bend the curve on readmission in patients with HF," they write.

PARADIGM HF was funded by Novartis. Desai receives consulting fees from Novartis, Merck, Sanofi, Janssen, Relypsa, and St Jude Medical. Disclosures for the coauthors are listed in the article. Mentz receives research support from the National Institutes of Health, Amgen, and Novartis, and O'Brien receives research support from Novartis.

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