Physicians' Academy for Cardiovascular Education

ARNI appears to positively modify course of disease in HFrEF

News - Nov. 17, 2014

The PARADIGM-HF study showed that the new agent LCZ696 was superior to the ACE-inhibitor enalapril in patients with heart failure with reduced ejection fraction (HFrEF) in lowering important endpoints including reducing risk of cardiovascular (CV) death and hospitalisation for HF. LCX696 is an ARNI (Angiotensine Receptor Neprilysin Inhibitor), which is an agent that had a dual protective effect on the heart, by stimulating natiruretic peptides and inhibiting the RAAS-system.
PARADIGM-HF is a randomised, double-blind, phase III study that compares the efficacy and safety of LCZ696 with the ACE-inhibitor enalapril, in over 8000 patients with HFrEF. Patients received LCZ696 or enalapril in addition to the best available medical treatment. New analyses of the PARADIGM-HF trial were now presented at the AHA congress.

Main results

  • As compared with enalapril, LCZ696 lowered the risk of sudden death with 20%.
  • LCZ696 also reduced first and subsequent admissions for HFrEF with 21% and 23% respectively, as compared to treatment with enalapril.
  • LCZ696 reduced hospital admission for CV reasons or any reason by 16%.
  • Patients treated with LCZ696 needed intensive home treatment less often (-16% vs. enalapril).
  • 30% fewer visits to the emergendy department as a result of quickly worsening of symptoms were seen after treatment with LCZ696, as compared with enalapril.
  • Patients stayed in the hospital equally long in both treatment groups, but patients on LCZ696 stayed less often on the intensive care (-18%) and needed IV drugs to stimulate heart pump function less often (-31%) than patients on enalapril.
  • Both patients and doctors felt that patients were doing better when treated with LCX696.


These results suggest that the ARNI LCZ696 can modify the course of disease of HFrEF. It appears that more is possible than just reducing the risk of dying or hospital admission. Experiences with LCZ696 teach that cardiac biomarkers such as NT-proBNP and troponin are lower than after treatment with enalapril, indicating that less cardiac stress and subsequent damage is done.
These results were published in Circulation during AHA 2014 :
Packer M, McMurray JJV, Desai AS, et al. Angiotensin-Neprilysin Inhibition and Clinical Progression in Surviving Patients with Heart Failure. Circulation. 2014


Press release Novartis 17 November 2014

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