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

Class Effect

The rationale of the HOPE study was based on the known actions of angiotensin II and the counteractions of ACE inhibitors, as well as on the meta-analyses of the SOLVD and SAVE trials.[1,2,4,18] Accordingly, the benefits of ramipril in the HOPE study are likely to depict a class effect for ACE inhibition. However, acceptance of the concept of a class effect requires denial of the fact that ACE inhibitors are structurally and physicochemically distinct. As much as the concept of a class effect for ACE inhibitors has been espoused, it has proven difficult to identify dose equivalence for the various positive effects of ACE inhibitors.[19,20]

For example, true dose equivalence for BP control has never been determined among the various ACE inhibitors. The impression that equivalent doses are readily identifiable in the hypertensive patient is merely an outgrowth of the unique dose response relationships of ACE inhibitors. These agents have a steep dose response at low doses, and thereafter, when given in higher doses, a relatively flat dose response curve.[21] This dose-response pattern lends itself readily to the concept of class effect. The prospect of a class effect is more dubious when CHF is considered for treatment with ACE inhibitors. The dosages of ACE inhibitors in CHF and the typically altered pharmacokinetics of these drugs in the CHF patient make it highly doubtful that a dose could be identified to allow one ACE inhibitor to ever truly be interchangeable with another.[22]

Where, then, does the concept of a class effect fall for tissue protection and, in particular, how does it relate to the HOPE study? Although at this time the answer to this question is unclear, it is likely that the physicochemical features of ramipril make it distinctive from a tissue protection viewpoint. However, if the HOPE results are ultimately proven to be derived from the BP changes observed in this study, there is little to distinguish ramipril from the nine other ACE inhibitors currently marketed in the United States.[23]