The Heart Outcomes Prevention Evaluation (HOPE) Study: Limitations and Strengths

Domenic A. Sica, MD; Division of Clinical Pharmacology and Hypertension, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA.

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Mechanisms of Benefit

The results of the HOPE study are highly suggestive of a specific vasculoprotective effect of ramipril above and beyond that anticipated from the modest BP reduction observed in this study. The mechanism for such vasculoprotection is speculative. Undoubtedly, some contribution to the positive outcome derived from a negation of cellular effects of angiotensin II, which include intimal and vascular smooth muscle cell proliferation as well as plaque instability. The relatively rapid benefit afforded patients in the HOPE study suggests an important role for plaque stabilization.[15] This hypothesis is particularly appealing, since recent studies with ramipril suggest that it has a minimal effect on reducing atherosclerosis.[16] Furthermore, the trial on reversing endothelial dysfunction the study[17] previously showed that ACE inhibition with quinapril improved endothelial dysfunction in normotensive patients who were without evidence of severe hyperlipidemia or CHF. Improvement of endothelial function is recognized as a means by which plaques can be stabilized.

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