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

Benefit Beyond Blood Pressure Reduction

The reduction in event rates, particularly for myocardial infarction, was much greater than would be expected from such a modest fall in BP as was observed in the ramipril treatment limb of this study. The often-quoted meta-analysis of BP lowering trials using older agents would suggest a reduction in stroke of 38% and in myocardial infarction of only 16% when diastolic BP is reduced by 4-5 mm Hg over a period of 4-5 years.[11] HOPE achieved this reduction in event rates with a fraction of this diastolic BP reduction. It has been argued that the high-risk populations in the HOPE study might, by reason of additional risk factors, have a steeper risk gradient for specific change in BP values. The risk reduction in the ramipril group, however, was much greater than would have been inferred from the BP risk gradient seen in the placebo arm of the HOPE study. Further evidence to support a major non-BP effect of ramipril is provided by a multiple regression analysis of the diabetics in the HOPE study, which showed a relative reduction in risk even after allowing for the effect of the reduction in BP.[12]

When the benefits of ramipril were related to quartile of baseline BP, greater risk reduction was shown in patients with higher baseline systolic BP (unpublished data).[24]