Alberto Foà, MD, PhD: Understanding Hypotension, Benefit, and LVEF in PARAGON-HF

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Alberto Foà, MD, PhD, discusses a PARAGON-HF analysis from ACC.24 examining treatment-related hypotension in people with HFmrEF/HFpEF.

Results from PARAGON-HF suggest a higher left ventricular ejection fraction (LVEF) was associated with an increased risk of hypotension and attenuated clinical benefit among patients with heart failure treated with sacubitril/valsartan (Entresto).

The data were presented by Alberto Foà, MD, PhD, a research fellow Brigham and Women’s Hospital, Harvard Medical School, at the American College of Cardiology’s (ACC) 2024 Annual Scientific Session in Atlanta, Georgia.

Hypotension is a frequent adverse event related to sacubitril/valsartan treatment, but data are limited on the predictors of treatment-related hypotension in heart failure with mildly reduced ejection fraction and heart failure. The drug’s benefit has been primarily observed in individuals with LVEF below normal levels.1,2

Hypotension was defined as a systolic blood pressure (SBP) of <100 mmHg and predictors were evaluated using time-updated multivariable Cox models. For analysis, the correlation between treatment, LVEF, the incidence of hypotension, and clinical outcomes was estimated with Poisson regression.1

Among 4,796 participants in PARGON-HF, 637 (13%) experienced hypotension and this was more frequent in those treated with sacubitril/valsartan (16% vs. 11%; P <.001). After documented hypotension, individuals exhibited a higher risk of cardiovascular death and total heart failure hospitalizations (adjusted rate ratio [RR], 1.68; 95% CI, 1.32 - 2.16; P <.001) and all-cause death (adjusted HR, 1.67; 95% CI, 1.32 - 2.11; P <.001).1

Analyses revealed that LVEF strongly modified the association between sacubitril/valsartan and the risk of hypotension (P interaction = .019). Those with LVEF >60% experienced significantly higher treatment-related risk of hypotension and were less likely to benefit from sacubitril/valsartan.1

For more insight into these findings, watch the full interview with Foà at ACC.24.


  1. Foà A, Claggett B, Pabon M, et al. SACUBITRIL/VALSARTAN, TREATMENT-RELATED HYPOTENSION, AND LEFT VENTRICULAR EJECTION FRACTION IN THE PARAGON-HF TRIAL. Presented at: American College of Cardiology (ACC.24) Annual Scientific Session. April 6 – 8, 2024. Atlanta, GA.
  2. Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019;381(17):1609-1620. doi:10.1056/NEJMoa1908655