Developing effective therapies for heart failure (HF) is challenging. Despite several clear successes in the development and delivery of pharmacotherapies for ambulatory patients with HF and reduced ejection fraction (HFrEF), efforts to modulate adverse neurohormonal activation beyond the renin-angiotensin-aldosterone system and the sympathetic nervous system generally have failed to improve outcomes further and have met with safety concerns including low blood pressure or changes in end-organ function. Recently, neprilysin inhibition in conjunction with angiotensin receptor blockade has been shown to improve outcomes. There is however no therapy approved specifically for HF with preserved EF (HFpEF) or for worsening chronic HF resulting in hospitalizations (WCHF; including acutely decompensated HF). Many patients with chronic HFrEF have poor outcomes despite receiving guideline-recommended therapies. Although preliminary results from some phase 2 trials have been promising, many subsequent phase 3 trials have been neutral or negative, highlighting a disconnect in the translational process between basic science discovery, early drug development, and definitive clinical testing in pivotal trials.
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(Circulation: Heart Failure.2016; 9: e002727) © 2016 by American Heart Association, Inc.)