Diabetes mellitus is a strong risk factor for cardiovascular and renal disease.
We investigated whether the angiotensin-converting-enzyme (ACE) inhibitor ramipril
can lower these risks in patients with diabetes.
3577 people with diabetes included in the Heart Outcomes Prevention Evaluation
(HOPE) study, aged 55 years or older, who had a previous cardiovascular event or at least
one other cardiovascular risk factor, no clinical proteinuria, heart failure, or low
ejection fraction, and who were not taking ACE inhibitors, were randomly assigned ramipril
(10 mg/day) or placebo, and vitamin E or placebo, according to a two-by-two factorial
design. The combined primary outcome was myocardial infarction, stroke, or
cardiovascular death. Over nephropathy was a main outcome in a substudy.
The study was stopped 6 months early (after 4.5 years) by the independent data
safely and monitoring board because of a consistent benefit of ramipril compared with
placebo. Ramipril lowered the risk of the combined primary outcome by 25% (95% CI
12-36, p=0.0004), myocardial infarction by 2% (6-36), stroke by 33% (10-50),
cardiovascular death by 37% (21-51), total mortality by 24% (8-37), revascularisation by
17% (2-30), and overt nephropathy by 24% (3-40, p=0.027). After adjustment for the
changes in systolic (2.4 mm Hg) and diastolic (1.0 mm Hg) blood pressures, ramipril still
lowered the risk of the combined primary outcome by 25% (12-36, p=0.0004).
Ramipril was beneficial for cardiovascular events and overt nephropathy in people
with diabetes. The cardiovascular benefit was greater than that attributable to the
decrease in blood pressure. This treatment represents a vasculoprotective and
renoprotective effect for people with diabetes.