Ankeet Bhatt, MD, MBA: Sacubitril/Valsartan vs ACEi/ARB in de novo HFmrEF/HFpEF

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A retrospective analysis of EHR data from ACC.24 provides insight into the effects of ARNI relative to ACEi/ARB in patients with newly diagnosed heart failure and an LVEF greater than 40%.

A comparative effectiveness analysis of data from the Optum Electronic Health Record dataset provides insight into the benefit of sacubitril/valsartan (Entresto) relative to angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in patients with newly diagnosed heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF).

“What we know from the way the FDA has labeled this in recent guidelines is that this therapy is efficacious over ACE or ARB, particularly in patients who have an [ejection fraction] ‘below normal’. Where I think we have had a reasonable data gap is on patients who are newly diagnosed with heart failure,” explained study investigator Ankeet Bhatt, MD, MBA,a research scientist at Kaiser Permanente Northern California and associate physician at Kaiser San Francisco Medical Center. “So, I think this provides us some reassurance that the benefits observed in most of the clinical trial populations can actually extend potentially to patients with de novo heart failure with mildly reduced and or preserved ejection fraction”

Presented at the American College of Cardiology 2024 (ACC.24) Annual Scientific Session, the retrospective, propensity-matched cohort study was designed with the intent of leveraging the database to determine the effects of sacubitril/valsartan, an angiotensin receptor/neprilysin inhibitor, relative to ACE inhibitors or ARB on all-cause hospitalization rates among patients with de novo heart failure and an ejection fraction greater than 40%.

From the database, investigators identified 458 patients meeting these criteria receiving sacubitril/valsartan who were matched in a 2:1 ratio to 916 patients receiving ACE inhibitors or ARB. This cohort had a mean age of 65.5 (Standard Deviation, 13.95) years, 62% were male, and 80% were Caucasian. The mean follow-up was 391 days in the sacubitril/valsartan group and 553 days in the ACE inhibitor or ARB cohort. Investigators pointed out 65% and 57% of the cohort had hypertension and ischemic heart disease, respectively.

Upon analysis, results indicated the annual rate of all-cause hospitalization was 0.79 hospitalizations per person-year in the sacubitril/valsartan group compared to 1.24 hospitalizations per person-year in the ACE inhibitor or ARB group (incidence rate ratio [IRR], 0.73, 95% confidence interval [CI], 0.59-0.92; P = .006). Further analysis indicated patients in the sacubitril/valsartan group had a rate of hospitalizations of 0.65 hospitalizations per person-year in the sacubitril/valsartan cohort compared to 1.01 hospitalizations per person-year among the ACE inhibitor or ARB cohort (IRR, 0.70, 95% CI, 0.55–0.88; P = .002).

For more insight into the study and how it informs clinical decision-making, check out our interview with Bhatt from ACC.24.

Relevant disclosures for Bhatt: Sanofi-Aventis.


Bhatt AS, Vaduganathan M, Jena BP, et al. Comparative effectiveness of sacubitril/valsartan versus angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in patients with de novo heart failure with mildly reduced and preserved ejection fraction. Eur J Heart Fail. Published online April 7, 2024. doi:10.1002/ejhf.3233