Update on ACEIs: Britannia Stadium 4.3.02

Several trials have shown that in some patients subgroups (e.g., in diabetic patients with proteinuria and in patients with left ventricular dysfunction/failure) ACEI have beneficial effects that are over and above those expected from their blood pressure lowering effect. Post-hoc analysis of trials of ACEI in patients with heart failure has shown an unexpected reduction in the occurrence of myocardial infarction (MI) even though BP in this population was low. These findings lead to the design of HOPE (Heart Outcomes Prevention Evaluation Study).

HOPE was a large, simple, randomized trial of Ramipril 10 mg od and vitamin E in patients (55 yr. of age or older) at high risk for cardiovascular events. The trial recruited patients with no LV dysfunction but::

80% had coronary artery disease 50% post MI

43% had peripheral vascular disease

11% had a stroke

38% had diabetes

47% had hypertension (treated and baseline BP was 139/79 mmHg)

66% had high cholesterol

High use of proven drugs :47% CCB,40% bB, 25% diuretics, 30-40% statins,78% aspirin

Treatment with Ramipril caused a modest reduction in BP (- 3.3/1.4 mmHg) which was associated with a risk reduction in MI, stroke, heart failure and all-cause death by 20,32,23 and 16% respectively. There was also an unexpected 34% reduction in the risk of developing diabetes and a 24% reduction in nephropathy. These benefits were consistently observed in a very broad range of high-risk patients (e.g., independent of age, sex or presence of diabetes) and in addition to other effective therapies. Treatment with Vit E made no difference.

These important findings have been obtained in patients with high risk for CHD and in diabetic patients, however, in patients with hypertension and lower CHD risk ACEI do not seem to confer extra protection when compared with conventional treatment, suggesting that when hypertension is the main risk factor, a large BP lowering effect may be the most important event as far as CHD prevention is concerned.

Is this a class effect? The results of the previous meta-analysis of trials of ACEI in heart failure suggests that this is the case, however, a recent study of the effect of ACEI inpatients with high risk of cerebrovascular disease (PROGRESS) showed a protective effect of Perindopril only when it was given in association with the diuretic Indapamide. In HOPE the relative risk reduction was the same in the presence or absence of diuretic or beta-blocker therapy.Handouts

Who should be given Ramipril (starting at 2.5 mg od titrated up to the maintenance dose of 10 mg od)? All patients with a history of coronary artery disease, stroke, peripheral vascular disease or diabetes plus at least another hjnmjcardiovascular risk factor (hypertension, high cholesterol, low HDL, smoking or microalbuminuria).

Doctor Barbara Casadei, Honorary Consultant in C.V. Medicine,

John Radcliffe Hospital, Oxford.