A new treatment for heart failure (HF) combining angiotensin 2 type 1 receptor blockade with inhibition of the widespread membrane-bound enzyme, neprilysin (NEP), seems likely to take treatment of chronic heart failure (CHF) a major step forward. Neurohormonal pathways are central to the evolution and progression of HF irrespective of the exact initial triggering cardiac injury or overload, and our current evidence-based treatments for this condition depend upon antagonism of the renin-angiotensin-aldosterone (RAAS) and sympathetic nervous (SNS) systems through prescription of angiotensin converting enzyme inhibitors (ACEIs), angiotensin 2 type 1 receptor blockers (ARBs), mineralocorticoid antagonists (MRAs) and blockers of beta-adrenoceptors (beta blockers). Properly deployed, these therapies reduce 1-year mortality to less than half than that suffered by patients with HF in the pre-1980s era. However, despite this clear impact upon the outcome of this deadly syndrome, 5-year mortality in CHF remains greater than 50%. This poor outlook plus the continuing high prevalence of HF mandates an ongoing search for more effective treatments.
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