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Sacubitril/Valsartan as a Cardiac Radioprotector.

Mihaela Ghita-Pettigrew1, Brianna N Kerr1, Kathryn H Brown1

  • 1The Johnston Cancer Research Centre, Queen's University Belfast, Belfast, United Kingdom.

International Journal of Radiation Oncology, Biology, Physics
|February 18, 2026
PubMed
Summary
This summary is machine-generated.

Sacubitril/valsartan (sac/val) shows promise in protecting the heart from radiation injury (RHI) by improving cardiac function and structure in mice. The drug was well-tolerated in both animal models and patients receiving thoracic radiation therapy.

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Area of Science:

  • Cardiology
  • Radiation Oncology
  • Pharmacology

Background:

  • The role of natriuretic peptides in radiation heart injury (RHI) is under-explored.
  • Preliminary data links RHI to decreased atrial natriuretic peptide (ANP).
  • Sacubitril/valsartan (sac/val) modulates the natriuretic peptide system and improves heart failure outcomes.

Purpose of the Study:

  • To evaluate sacubitril/valsartan (sac/val) as a radioprotective agent against radiation-induced heart injury.
  • To investigate the safety and preliminary efficacy of sac/val in a mouse model of RHI.
  • To explore ANP dynamics and sac/val safety in patients undergoing thoracic radiation therapy.

Main Methods:

  • A partial-heart irradiation mouse model was used, with mice receiving irradiation with or without sac/val.
  • Cardiac function and structure were assessed over 30 weeks using echocardiography and electrocardiography.
  • Plasma ANP levels were measured, and a retrospective clinical series examined ANP dynamics and sac/val safety in patients.

Main Results:

  • Sac/val significantly improved cardiac remodeling, systolic/diastolic function, and electrophysiological parameters in irradiated mice.
  • Functional cardiac protection by sac/val was evident as early as 10 weeks post-irradiation.
  • Sac/val was well-tolerated in animals and patients, with no adverse effects reported. Clinical data indicated dynamic ANP changes during radiation therapy.

Conclusions:

  • Sacubitril/valsartan (sac/val) effectively attenuated structural and functional radiation heart injury in a preclinical model.
  • The drug demonstrated good tolerability when co-administered with radiation in both animal and early clinical investigations.
  • Further research into sac/val's potential as a cardiac radioprotector is warranted, supported by observed ANP dynamics and safety profiles.