ACE and heart failure: The recent PARADIGM-HF multicenter randomized controlled trial [116] tested a drug that is a combination of the ARB valsartan and the neprilysin inhibitor sacubitril on 8399 patients with heart failure and a reduced LVEF, reporting a reduction of 20% in death from cardiovascular causes or hospitalization for heart failure as compared with the ACE inhibitor enalapril alone at maximum dosage (p < 0.001).