REN and heart failure: An important aspect of these additional mechanisms of therapeutic benefit from RAS inhibition is that combination of ACE inhibitor, ARB, and/or renin inhibitor therapies may block some of these mechanisms of benefit, thereby explaining the many clinical studies, apart from heart failure (49), that showed no additional benefit from combination of ACE inhibitor, ARB, and renin inhibitor therapies (47, 48, 50–53).