Sacubitril/valsartan reduces incident anaemia and iron therapy utilization in heart failure: The PARAGON-HF trial

Henri Lu; Brian L Claggett; Milton Packer; Marc A Pfeffer; Carolyn S P Lam; Michael R Zile; Akshay S Desai; Pardeep Jhund; Martin Lefkowitz; John J V McMurray; Scott D Solomon; Muthiah Vaduganathan

doi:10.1002/ejhf.3414

Sacubitril/valsartan reduces incident anaemia and iron therapy utilization in heart failure: The PARAGON-HF trial

Eur J Heart Fail. 2024 Sep 1. doi: 10.1002/ejhf.3414. Online ahead of print.

Authors

Affiliations

¹ Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
² Division of Cardiology, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland.
³ Baylor University Medical Center, Baylor Heart and Vascular Institute, Dallas, TX, USA.
⁴ National Heart Centre Singapore, Singapore, Singapore.
⁵ Medical University of South Carolina, Charleston, SC, USA.
⁶ BHF Glasgow Cardiovascular Research Centre, Glasgow, UK.
⁷ Novartis, East Hanover, NJ, USA.

PMID: 39217577
DOI: 10.1002/ejhf.3414

Abstract

Aims: Renin-angiotensin system inhibitors (RASi) have been shown to lower haemoglobin levels, potentially related to reductions in erythropoietin levels and haematopoiesis. We examined whether sacubitril/valsartan might attenuate this effect of RASi alone on incident anaemia in patients with heart failure (HF) with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF).

Methods and results: PARAGON-HF was a global, multicentre randomized clinical trial of sacubitril/valsartan versus the RASi valsartan in patients with HF and left ventricular ejection fraction ≥45%. We evaluated haemoglobin trajectory and risks of incident anaemia and new iron therapy initiation during follow-up. Among 4795 participants, 1111 (23.2%) had anaemia at randomization and 5.6% were treated with iron at baseline. Over a median follow-up of 2.9 years, patients with anaemia were at significantly higher risk for total HF hospitalizations and cardiovascular death, compared with those without anaemia (21.6 vs. 11.5 per 100 patient-years; adjusted rate ratio 1.31; 95% confidence interval [CI] 1.12-1.54; p = 0.001). Sacubitril/valsartan slightly slowed the decline in haemoglobin levels by 0.1 g/dl (95% CI 0.0-0.2 g/dl; p = 0.005). Participants treated with sacubitril/valsartan were at significantly lower risk of developing anaemia (30.3% vs. 37.6%; hazard ratio [HR] 0.76; 95% CI 0.68-0.85; p < 0.001) and starting iron therapy (8.1% vs. 10.0%; HR 0.81; 95% CI 0.67-0.97; p = 0.026). Treatment effects of sacubitril/valsartan versus valsartan on total HF hospitalizations and cardiovascular death were consistent among patients across the haemoglobin spectrum (p_interaction = 0.60).

Conclusions: Among patients with HFmrEF/HFpEF, treatment with sacubitril/valsartan resulted in modestly smaller declines in haemoglobin, lower rates of incident anaemia, and fewer new initiations of iron therapy compared with RASi.

Clinical trial registration: ClinicalTrials.gov ID NCT01920711.

Keywords: Anaemia; Heart failure; Sacubitril/valsartan.

Associated data

ClinicalTrials.gov/NCT01920711

Grants and funding

Novartis