Angiotensin Receptor Neprilysin Inhibitor for the Treatment of Cardiovascular Diseases: A New Approach

A new revolution has begun in the management of chronic heart failure with reduced ejection fraction (CHFrEF). The new blockbuster angiotensin receptor neprilysin inhibitor (ARNI/LCZ696) has evoked a new concept of multisystem neurohormonal modulation, and indeed, this has shown an additional decrease in cardiovascular (CV) mortality on top of all standard evidence-based drugs for the treatment of CHFrEF, i.e., angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), beta blockers, and mineralocorticoid receptor antagonists (MRAs) coupled with diuretics. LCZ696 has two drugs, ARB valsartan and neprilysin inhibitor sacubitril, fused in a molecular complex. The combination provides a dual strategy of combating neurohormonal activation in heart failure (HF), i.e., by blocking harmful effect of renin-angiotensinaldosterone system by valsartan and simultaneously increasing the activation of vasoactive peptides by inhibiting neprilysin. It was evaluated in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, which produced a statistically significant dramatic reduction of 20% in the primary end point of a composite of death from CV cause and hospitalization for HF. The combination is well tolerated, and side effects are minimal. LCZ696 has been approved for clinical use and has been endorsed by the European Society of Cardiology and American College of Cardiology/American Heart Association/ Heart Failure Society of America 2016 guidelines. What is very exciting is that it has emerged as a replacement therapy for class I A drug (ACE/ARB) rather than as a mere add-on therapy, which is the usual story with any new drug. The drug is likely to be available in India in the near future.