Anyone with a history of vascular disease — coronary, cerebral or peripheral — should be treated with the ACE inhibitor ramipril. This was the recommendation made by presenters of the Heart Outcomes Prevention Evaluation (HOPE) study on August 31 at the 21st Congress of the European Society of Cardiology in Barcelona, Spain.
To a packed auditorium, Professor Peter Sleight (co-chairman of the HOPE study and emeritus professor of cardiovascular medicine at Oxford university) presented data showing that, in patients aged 55 and over with a history of vascular disease, a daily dose of ramipril for four years reduced the risk of cardiovascular death, stroke or myocardial infarction by 22 per cent. Myocardial infarction was reduced by 20 per cent, stroke by 32 per cent, and diabetes by 31 per cent. The benefits were seen across all patient groups, regardless of age, sex or blood pressure. They occurred within three to four months of the start of treatment and increased throughout the study with no signs of a plateau in effect.
“The implications of the study are quite staggering. Not only is vascular disease very common but we have shown we can prevent an enormous amount of future disability, strokes, infarctions and surgery,” concluded Professor Sleight. “It has been a very exciting trial to belong to and, at my age, to be involved in something like this has been remarkable,” he added. The trial, set up to investigate the benefits of ACE inhibitor therapy seen in earlier heart failure studies and other studies, was sponsored by the Canadian Medical Research Council and Heart and Stroke Foundation, with commercial funding from companies including Hoechst Marion Roussel and Astra Zeneca.
Established to investigate the effect of ramipril and vitamin E on vascular morbidity and mortality over six years, HOPE was conducted in 267 centres in 19 countries under the chairmanship of Professor Sleight and Professor Salim Yusuf, from McMaster university, Canada. The trial was stopped early, in March this year, on the instruction of the data and safety monitoring board.
Over 9,500 high risk patients were randomised to ramipril (up to 10mg/day) or placebo and a similar number to vitamin E or placebo. While highly significant benefits were seen with ramipril, no changes in vascular risk were seen with vitamin E treatment. However, this arm of the study is continuing to investigate the long-term effects of therapy.
The study organisers are attributing the benefits of ramipril treatment to the plaque stabilising rather than the blood pressure lowering effects of the drug. This is because blood pressure at baseline was well controlled, often with antihypertensive therapy, with a mean level of 139/79mmHg, and only a small further decline was seen by the end of the trial. The study organisers have not dismissed a potential role for vitamin E and suggest that, since this is likely to have a preventive rather than a stabilising effect on plaques, any benefits may take longer to accumulate.
“Vitamin E is not dead. We are disappointed with the results but it is possible that the three or four years of the study was too short to show an effect and this is why we are continuing with this part of the study,” said Professor Sleight.
Until the beneficial effect of ramipril could be shown to be a class effect, he advised doctors to prescribe ramipril to their high risk vascular patients rather than other ACE inhibitors. Professor Yusuf pointed out that, since the price of ramipril came in the mid range of ACE inhibitor therapy, cost should not be an issue. — from Jenny Bryan.