PARADIGM-HF study observed clinical outcomes
after treatment by new
drug LCZ696 or
enalapril in patients with systolic chronic
heart failure. It was randomized double-blind trial with
LCZ696 (200 mg twice a day) and
enalapril (10 mg twice a day). 8442 patients were enrolled with NYHA class II or III and left ventricular ejection fiction of 40% or less. Study drugs were added to other recommended medication. The trial was prematurely terminated after median follow-up of 27 months. The primary endpoint of the study was a combination of cardiovascular mortality and the first hospitalization for
heart failure.
LCZ696 drug, an inhibitor of
angiotensin receptor and
neprilysin (Arnie), has led to a reduction in the primary composite target by 20% (p <0.001). The treatment has decreased cardiovascular mortality by 20%, p <0.001 and hospitalization for worsening
heart failure by 21%, p <0.001.
LCZ696 has also decreased total mortality by 16%, p <0.001. The use of
LCZ696 has been accompanied by frequent symptomatic
hypotension and
hypotension with a decrease in systolic blood pressure below 90 mm Hg, however,
LCZ696 was less often associated with an increase in serum
creatinine and serum
potassium than
enalapril. In addition,
cough has occurred less frequently after
LCZ696 than after
enalapril. Discontinuation of
therapy occurred in 746 patients (17.8%) treated with
LCZ696 and in 833 patients (19.8%) treated with
enalapril (19.8%) (p = 0.02). PARADIGM-HF study has also shown superiority of
LCZ696 compared to
ACE inhibitors in stable outpatients with chronic
systolic heart failure NYHA stages II and III. Therefore,
LCZ696 is more effective than
ACE inhibitors (and
angiotensin receptor blockers). Moreover, it is well tolerated.
LCZ696 seems to replace the
ACE inhibitors in mentioned patients. The authors also discuss the results of the first randomized study PARAMOUNT investigating
LCZ696 efficacy in patients with chronic
heart failure and good left ventricular ejection fraction.