“In the moneyed world of big Pharma the biggest news this year has the been the licensing of a new combination therapy to treat cardiac failure. Novartis the company behind the development of this combination therapy are ecstatic. Their drug, Entresto, is a first in class medicine, or more importantly a combination therapy, (an ARNI, Angiotensin Receptor Neprilysin Inhibitor) that reduces the strain on the failing heart. In summary, compared to the old standard drug enalapril, it: (1) reduced the risk of death from cardiovascular causes by 20%, (2) heart failure hospitalisations by 21% and the risk of all-cause mortality by 16%. Believe me when I say these results are the biggest development in the treatment of cardiac failure since the 1980’s. Why did it take so long to get here? Simple, it required research, new biology, a change in the treatment paradigm, a bold group of investigators, risk and deep pockets.”
BACKGROUND: Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients.
METHODS AND RESULTS: We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril.
CONCLUSIONS: Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition.