A Q and A on the Findings of the HOPE Trial
Special commentaries by:
Pierre Larochelle1,
Ellen P. Burgess2,
Ernesto L. Schiffrin3,
Simon Kouz4, and
Michael Adams5
1Assistant Director, Clinical Research Centre,
Centre Hospitalier de l'Université de Montréal-Campus Hôtel-Dieu,
Professor of Pharmacology,
Université de Montréal, Montreal, Quebec.
2Active Staff & Director, Foothills Medical Centre,
Associate Professor of Medicine,
University of Calgary, Calgary, Alberta.
3Director, Multidisciplinary Hypertension Group,
Hypertension & Lipid Clinic and Clinical Research Institute of Montreal, and
Professor of Medicine, Université de Montréal, Montreal, Quebec.
4Chief, Cardiology Service & Director,
Clinical Research Unit in Cardiology,
Centre Hospitalier Régional de Lanaudière, Joliette, Quebec.
5Head, Department of Pharmacology and Toxicology,
Queen's University, Kingston, Ontario.
Did the Results of the HOPE Trial Come as a Surprise?
Dr. Ernesto L. Schiffrin. Not at all. Our research group has been conducting numerous studies on ACE inhibitors for a number of years. In fact, we were among the first to demonstrate the vascular protective effects of these agents. Therefore the results of HOPE come as no surprise, but it is always necessary to confirm in real life what is observed in the laboratory.
Dr. Pierre Larochelle. Those kinds of results were to be expected. It may be the magnitude of the benefits that took many by surprise.
Dr. Ellen Burgess. It has been shown repeatedly that treating hypertension is very beneficial. Also, ACE inhibitors have been shown in an impressive number of studies in post-MI patients, CHF, etc, to reduce morbidity and mortality so it was to be expected that the high-risk patients in the HOPE trial would benefit from ACE inhibitor therapy.
Dr. Simon Kouz. Our hospital was very much involved in the HOPE trial, and the study was designed to confirm what we suspected based on earlier trials with ACE inhibitors.
The results of HOPE are the logical continuation of other completed or ongoing studies using ACE inhibitors. HOPE constitutes the consecration of the unique role of ACE inhibitors in high-risk patients, especially diabetics.
Dr. Michael Adams. I expected these results, but given the fact that patients in the HOPE trial were already receiving treatment with other agents (i.e., ASA, beta-blockers, calcium antagonists, statins, etc.), it was surprising that benefit became evident after only one year.
What is the most significant result from the HOPE trial?
Dr. Ernesto L. Schiffrin. The HOPE trial is the confirmation that blocking the renin-angiotensin-aldosterone (RAA) system in patients at high risk for CVD is associated with a dramatic improvement in the risk of cardiovascular events.
Dr. Pierre Larochelle. It is the first randomized, controlled, study which tried to differentiate the benefits of BP reduction versus the benefits associated with the vascular effect of ACE inhibitors. It was designed to establish whether ACE inhibitors would have a protective vascular effect at non-antihypertensive doses. It was a success in that it demonstrated a protective effect on the cardiac and cerebral vessels; however, there were two factors which make it impossible to draw definitive conclusions: 1) there was a slight antihypertensive effect which may be responsible for part of the observed benefits, and 2) patients with elevated systolic BP benefit more from an ACE inhibitor and may be responsible for a significant portion of the overall benefit. That being said, the whole study population did benefit from ACE inhibitor therapy.
Dr. Ellen Burgess. The results of the HOPE trial are somewhat unclear due to certain methodological problems such as the BP may not have been measured frequently enough. In addition, the mixed population makes it difficult to interpret the results and it would have been interesting to have other parameters monitored such