Posted on Sept. 3: Sustained prevention of cardiovascular events and diabetes with Ramipril: study
After seven years of follow-up, the HOPE-TOO study has demonstrated a sustained effect of ramipril on the prevention of cardiovascular disease and no preventive effects of vitamin E on either cancer or cardiovascular disease. It did demonstrate no preventive effects of vitamin E on either cancer or cardiovascular disease — a sustained effect of ramipril on the prevention of cardiovascular disease.
HOPE-TOO is a continuation of the HOPE (Heart Outcomes Prevention Evaluation) study begun in 1994. The study looked at the effects of ramipril, an angiotensin-converting-enzyme inhibitor, and vitamin E on the prevention of cardiovascular disease in a high-risk population.
The HOPE-TOO results were presented today (Sept. 3) at the European Society of Cardiology Meeting in Vienna, Austria. The study was conducted by the Population Health Research Institute at McMaster University and Hamilton Health Sciences in Hamilton, Ontario, Canada.
The ramipril arm of the study was stopped six months early in April 1999 due to clear reductions (a 22 per cent risk reduction) in heart attacks, stroke or death due to cardiovascular causes. The vitamin E arm of the study completed the five-year course as scheduled, and while there was no evidence of protection against cardiovascular disease, the data as to whether or not vitamin E would prevent cancer were unclear.
The HOPE-TOO (HOPE-The Ongoing Outcomes) study began in November 1999 and evaluated whether the cardiovascular benefits seen with 4.5 years of treatment with ramipril were sustained and, secondly, whether longer-term treatment with vitamin E was protective against the development of cancer and cardiovascular disease. Of the original 9,541 patients and 267 centres entered in HOPE, 6,786 patients and 174 centres agreed to extended follow-up until September 2002.
There was continued benefit in the prevention of major cardiovascular events for those people originally on ramipril. At the end of the seven-year follow-up there was a 19 per cent risk reduction for those who were originally assigned to the ramipril group. There appeared to be incremental reductions in heart attacks as well as in the development of diabetes. This incremental benefit was observed in spite of the fact that 67 per cent of those in placebo group started taking ramipril in 1999, when the ramipril arm of the study closed.
Jackie Bosch, project manager and assistant clinical professor at McMaster University said, “Not only were the benefits of ramipril sustained, but the benefits in reducing heart attacks and diabetes were further enhanced.”
After seven years of treatment with vitamin E there was no impact on cancer or on cardiovascular disease. However there was a statistically significant 17 per cent increase in the risk of congestive heart failure. Eva Lonn, co-principal investigator and professor of medicine at McMaster University said, “The lack of benefit of vitamin E on cancer and cardiovascular disease, coupled with the increase in heart failure raises concerns about the use of vitamin E.”
Salim Yusuf, co-principal investigator and professor of medicine at McMaster University, said the additional study period was beneficial.
“This extension emphasizes that to understand the full benefits or full harm from various prevention or treatment strategies often requires extended observation of patients for several years after the end of trials. The HOPE-TOO results confirm the sustained value of ramipril and lack of benefit of vitamin E.”
The Population Health Research Institute conducts research internationally in the areas of prevention and treatment of cardiovascular disease and diabetes. It is currently conducting over 15 major studies in 66 countries.
The HOPE and HOPE-TOO studies were supported by grants from the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Ontario, Aventis Pharmaceuticals, the Natural Source Vitamin E Association, Astra-Zeneca, King Pharmaceuticals and NEGMA.
