Mechanisms of cardiovascular risk reduction with ramipril: insights from HOPE and HOPE substudies

Angiotensin converting enzyme (ACE) inhibitors decrease angiotensin formation, prevent breakdown of bradykinin, and may also act on other peptides of the renin-angiotensin system. Thus, these agents have many effects that can potentially protect the coronary and peripheral vascularature. Which of these “theoretical” mechanisms account for the clinical benefit observed in The Heart Outcomes Prevention Evaluation (HOPE) trial? While the answer to this question is complex and cannot be fully answered, several potential mechanisms have been explored within HOPE and its substudies. These studies demonstrate that ramipril has potent effects on atherosclerosis progression and plaque stabilization as well as on myocardial structure and function. Ramipril also improves glucose metabolism. These effects are dose-dependent but largely blood pressure independent.