Neprilysin Inhibition as a PARADIGM Shift in Heart Failure Therapy.

Heart failure is a growing global public health problem. With the aging population, increased risk factors for heart failure development, and better survival after myocardial infarction, the prevalence is only expected to increase in the coming years. Although existing therapies have improved the clinical course of heart failure patients, new approaches are urgently needed to enhance quality of life and reduce morbidity and mortality. However, there has been little progress in the treatment of chronic heart failure in the past decade with only two new drugs approved by the US FDA over this time. Better understanding of the neurohormonal axis of heart failure has lead to the development of LCZ696, a first-in-class novel agent that acts as an angiotensin receptor blocker and neprilysin inhibitor. In the PARADIGM-HF study, LCZ696 was superior to an angiotensin-converting enzyme inhibitor in reducing mortality and HF hospitalizations and improving quality of life across a broad spectrum of symptomatic patients with heart failure with reduced ejection fraction. While evaluation of long-term effects is still needed, the completed trials on LCZ696 demonstrate that the drug is generally well-tolerated with a safe side effect profile. LCZ696 should be strongly considered as a favorable alternative to angiotensin converting enzyme inhibitors and angiotensin receptor blockers in appropriate heart failure patients.