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Angiotensin receptor neprilysin inhibitors: LCZ696 could change course of heart failure for patients

New data on investigational medicine, LCZ696, for patients with heart failure with reduced ejection fraction ( HFrEF ) have shown it has the potential to change the course of the disease for patients.
In August 2014, topline results from the landmark PARADIGM-HF study showing LCZ696 was superior to ACE inhibitor Enalapril on key endpoints, including significantly reducing the risk of cardiovascular death or heart failure hospitalization were presented.

The new analyses, presented for the first time at the American Heart Association Scientific Sessions 2014, have shown that versus Enalapril, LCZ696 significantly: reduced the risk of dying suddenly by 20%, in HFrEF patients 45% of cardiovascular deaths and 36% of all cause deaths are sudden; reduced first and subsequent HFrEF hospitalizations by 21% and 23% respectively; reduced hospitalizations for a cardiovascular reason or for any reason both by 16%; reduced the need for more intense treatment at home by 16%; reduced emergency room visits because of rapid symptom worsening by 30%.

When hospitalized, LCZ696 and Enalapril patients remained under care for approximately the same time, but those on LCZ696 had 18% fewer stays in intensive care and were 31% less likely to need IV drugs to help their heart pump.
Patients' reports of how well they felt and doctors' assessments of disease severity were also significantly better with LCZ696 than Enalapril.

Analysis of cardiac biomarkers ( NTpro-BNP and troponin ), substances that indicate the progression of cardiac disease and risk, showed levels were consistently lower with LCZ696 than Enalapril, reflecting reduced heart stress and subsequent damage.

LCZ696, an ARNI ( Angiotensin Receptor Neprilysin Inhibitor ), acts to enhance the protective neurohormonal systems of the heart ( NP system ) while simultaneously suppressing the harmful system ( the RAAS ).
Currently available medicines for HFrEF only block the harmful effects and mortality remains very high with up to 50% of patients dying within 5 years of a diagnosis of heart failure.

PARADIGM-HF is a randomized, double-blind, phase III study that evaluated the efficacy and safety profile of LCZ696 versus Enalapril ( an ACE inhibitor ) in 8,442 patients with HFrEF.
The baseline characteristics showed the patients enrolled were typical HFrEF patients with NYHA Class II-IV heart failure.
PARADIGM-HF was specifically designed to see if LCZ696 could decrease cardiovascular mortality by at least 15% versus Enalapril.
Patients received LCZ696 or Enalapril in addition to current best treatment regimen.
The primary endpoint was a composite of time to first occurrence of either cardiovascular death or heart failure hospitalization, and it is the largest heart failure study ever done. ( Xagena )

Source: Novartis, 2014