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.

In This Article


The Heart Outcomes Prevention Evaluation (HOPE) study was a landmark study employing the angiotensin-converting enzyme (ACE) inhibitor ramipril in a patient population predestined for vascular events. This study found that a 10-mg dose of ramipril in comparison with placebo significantly reduced, by 22%, the incidence of death, myocardial infarction, stroke, and death from cardiovascular causes. This improvement in outcome could not be completely explained by the degree to which blood pressure was reduced with ramipril. This strongly suggests a mechanism for the beneficial effects of ramipril unrelated to blood pressure and presumably related to interruption of the renin-angiotensin axis at the tissue level. At the same time in the same population, Vitamin E in a dose of 400 IU had no identifiable effect of significance. Whether the observed findings in the HOPE study are a "class effect" for all ACE inhibitors remains to be determined. Ramipril is the first ACE inhibitor shown to prevent ischemic events in high-risk patients without left ventricular dysfunction. Until results become available from other ACE inhibitor trials currently underway, which involve populations similar to those included in the HOPE study, it is premature to assume that the benefits of ramipril in the HOPE trial are a class effect.

The concept of inhibiting the renin-angiotensin system (RAS) to treat hypertension was first implemented in the early 1980s with the availability of angiotensin-converting enzyme (ACE) inhibitors. Shortly thereafter, the importance of RAS inhibition was extended to the management of congestive heart failure (CHF) and subsequently consolidated in several landmark studies, including the Studies of Left Ventricular Dysfunction (SOLVD)[1,2] and the Vasodilator Heart Failure Trial II (V-HeFT II).[3] Other studies in the post-myocardial infarction population, including the Survival and Ventricular Enlargement (SAVE) trial,[4] the Acute Infarction Ramipril Efficacy (AIRE) trial,[5] and the Trandolapril Cardiac Evaluation (TRACE) study,[6] revealed an important role for ACE inhibitors in decreasing morbidity and mortality in this highly at-risk population. Over the last decade, considerable evidence has now been amassed in support of the concept that the RAS is a risk factor for vascular disease, independent of other cardiovascular risk factors. These studies, both experimental and clinical, suggest that patients at risk for end events can benefit from inhibition of the RAS system, as might be accomplished with ACE inhibitor therapy.