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

Population at Risk and Study Aims

The aims of the HOPE study were to answer two questions. First, would an ACE inhibitor reduce the risk of coronary heart disease events, death, and stroke in high-risk patients without heart failure? Second, does Vitamin E reduce the risk for these same events? Experimental and clinical evidence existed in support of both of these hypotheses, thereby justifying their study. Ramipril, the ACE inhibitor employed in this study, was originally approved in 1991 for the treatment of hypertension, and has since gained an indication for reducing the risk of death and heart failure among patients who have experienced a myocardial infarction. Of the patients in the HOPE study, 27% were women, 55% were at least 65 years of age, 88% had cardiovascular disease, 47% had hypertension, and 38% had diabetes.

The study was unusual in that the trial interventions were added, in the majority of patients, to other proven medications, which would be expected to reduce the impact of the trial regimen. At baseline, 76% of the subjects were on an antiplatelet agent (primarily aspirin), 45% were on a calcium channel blocker, 40% were on a ß blocker, 15% were on a diuretic, and 30% were on a lipid-lowering agent. During the 4.5 years of the study, the use of all of these agents increased, with the exception of calcium channel blockers, which decreased in use by 5%. Perhaps as a result of these background therapies, the baseline BP was normal -- 139/79 mm Hg -- in the overall population, despite a history of hypertension in almost 50% of the study population.

The reduction in BP attributable to ramipril was modest; the difference was about 3-4 mm Hg systolic and 1-2 mm Hg diastolic between ramipril- and placebo-allocated patients. However, the HOPE study was not designed to be a hypertension trial and the frequency with which BP readings were obtained makes it difficult to interpret the observed BP differences. The ramipril treatment arm of this study differed from other studies in three ways. First, the baseline BP was at or near normal in the study participants; second, the treatment-induced reduction in BP was very modest; and finally, there was extensive use of concomitant antihypertensive, antiplatelet, and lipid-lowering therapies, although these were equally distributed in the ramipril and placebo treatment groups.