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

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.

References:

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