Neutral Peptidase Inhibitors

End-stage heart disease has a high mortality. Despite considerable advancement in therapy, the overall prognosis remains dismal. This has spurred the search for newer agents that can effectively attenuate the aberrant physiological changes evident in heart failure. Multiple clinical trials have made it evident that opposing the aberrant neurohormonal stimulation is associated with a better outcome. Thus ACE inhibitors which reduce afterload by reducing the formation of angiotensin II have a better effect on mortality and morbidity than hydralazine, a direct vasodilator. Similarly, certain studies albeit small ones have shown that natriuretic agents which promote diuresis by augmenting the body’s defence against the abnormal neurohormonal milieu evident in heart failure might have a better effect on long-term prognosis than the symptomatically much more effective diuretics. These findings have led to the development of novel agents that not only block the overstimulated renin-angiotensin system but also augment the natriuretic peptide system, the body’s defence against the abnormal neurohormonal milieu that is evident in heart failure. This article reviews the clinical pharmacology of novel agents that augment the natriuretic peptide system in the body.