Modulation of the Renin-Angiotensin-Aldosterone System in Heart Failure

The renin-angiotensin-aldosterone system (RAAS) is well-established and continues to be pursued as a therapeutic target in the treatment of heart failure, predominantly due to the success of agents that block RAAS in clinical trials of systolic heart failure. The optimal treatment of heart failure patients with preserved ejection fraction (HFpEF), however, remains unclear. Early trials of direct renin inhibitors have suggested that these agents may play a role in HFpEF, but recent clinical trial results have not been encouraging. Preliminary trials of angiotensin-receptor/neprilysin inhibitors look promising. Whether results with these or other drugs will alter current recommendations remains to be seen. In this review, we assess the current understanding of the role of RAAS modulation in heart failure.