The HOPE study93 demonstrated that ACE inhibition with ramipril therapy decreased rates of death and MI in high-risk patients without left ventricular dysfunction or heart failure. This RCT included 9297 patients with a history of CAD, peripheral vascular disease, stroke, or 2 or more cardiovascular risk factors, one of which had to include diabetes mellitus. The patients were followed for 5 years for a primary outcome composite of MI, stroke, or death from cardiovascular causes. Inhibition of ACE significantly decreased MI, stroke, and death from cardiovascular causes separately and as the primary outcome composite (RR, 0.78; P<.001). In addition, death from any cause was significantly reduced, and many clinical events, for example, worsening angina, were also significantly reduced. Inhibition of ACE was beneficial in each of the subgroups in the study and was independent of other medications the patients were taking. Thus, ACE inhibition in high-risk patients without known heart failure or ventricular dysfunction significantly decreased clinical events associated with atherosclerosis and ischemia.99 The decrease in clinical events is supported by the PART-2. Although the trial was not designed or powered to assess clinical end points, it observed trends toward decreased cardiovascular deaths and events (RR, 0.43 and 0.66, respectively). Further support comes from the ACE inhibition revascularization study,100 a 3-year RCT of 159 patients randomized to receive ramipril (5 mg/d) after revascularization by percutaneous transluminal coronary angioplasty or coronary artery bypass graft, which showed a significant decrease in the primary end point of cardiac death, acute MI, or clinical heart failure (RR, 0.58; P = .03). Although this study accepted patients with and without heart failure, the results were consistent across subgroups, including patients with normal ejection fractions. Finally, the PROGRESS (Perindopril Protection Against Recurrent Stroke Study)94 found that ACE inhibition in 6105 patients with a history of cardiovascular accidents or transient ischemic attacks reduced the secondary outcome of cardiac death or acute MI (RR, 0.74; P<.05).