Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Oct 2013
ReviewRenin-angiotensin-aldosterone system inhibitors in heart failure.
Heart failure (HF) is a very common condition that, despite advances in treatment, carries significant morbidity and mortality. Although there is good evidence for the treatment of HF with reduced ejection fraction (HFrEF), the treatment for HF with preserved ejection fraction (HFpEF) is not well defined. The renin-angiotensin-aldosterone system (RAAS) has been shown to be an effective target in the treatment of HFrEF using angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone blockade, although the evidence in HFpEF is less clear. This review aims to look first at the evidence for these drugs, and second at the newer drugs that act on the RAAS, namely, direct renin inhibitors, neutral endopeptidase inhibitors, vasopeptidase inhibitors, and angiotensin receptor blockers.
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Clin. Pharmacol. Ther. · Oct 2013
First-in-class angiotensin receptor neprilysin inhibitor in heart failure.
Neprilysin inhibitors augment the natriuretic peptide system by preventing the breakdown of atrial natriuretic peptide and B-type natriuretic peptide. LCZ696, an angiotensin receptor neprilysin inhibitor composed of a neprilysin inhibitor prodrug and the angiotensin receptor antagonist valsartan, has proven effective in hypertension, has shown promise in a pilot trial of heart failure with preserved ejection fraction, and is being tested in a large outcomes trial of heart failure with reduced ejection fraction. A preserved ejection fraction outcomes trial is beginning.