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Alerts > The Angiotensin-Converting Enzyme Inhibi...
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The Angiotensin-Converting Enzyme Inhibitor Ramipril Is Found to Prevent Cardiovascular Events in Diabetes Patients
Diabetes is a major risk factor for cardiovascular events, with diabetes patients two to four times more likely to die of cardiovascular causes than those without the disease. In patients with high cardiovascular risk, recent findings have suggested that the inhibitor ramipril prevents cardiovascular events.
The Heart Outcomes Prevention Evaluation (HOPE) study was designed to confirm these findings generally in high-risk patients and specifically in diabetes patients. A total of 3,577 diabetes patients were randomized to 10 mg of ramipril or placebo.
After 4.5 years of follow-up, ramipril reduced the risk of the primary cardiovascular outcome of myocardial infarction or stroke, or death from cardiovascular causes, by 25% (P=0.0004), with the survival curves for the treatment and placebo arms beginning to diverge at about 6 months. Ramipril also reduced the individual risks for each of the three components of the primary outcome, with a 37% risk reduction in cardiovascular death, a 22% risk reduction in myocardial infarction, and a 33% risk reduction in stroke.
To address the possibility that the effect of ramipril was due to its well-known blood pressure–lowering effect, the researchers controlled for change in blood pressure during the study and found that ramipril still reduced the risk of the primary outcome by 25%.
HOPE also examined the effect of ramipril on diabetic nephropathy. Screening for was conducted at baseline, at the 1-year mark, and at study end by measuring the urine albumin:creatinine ratio, which was, in turn, confirmed by timed urine collection. Ramipril was found to significantly reduce the risk of (as defined by an albumin-creatinine ratio >36 mg/mmol) by 22% (P=0.045), and overt nephropathy, laser therapy for diabetic retinal disease, or dialysis by 15% (P=0.05).
The only adverse effect of ramipril was a 5% absolute excess of cough in the treatment arm relative to the placebo arm. The researchers concluded that inhibition with ramipril represents a new and preventive therapy for diabetes patients, and that the preventive effects of ramipril for macrovascular disease are independent of changes in blood pressure.
The study subjects were asked whether they had diabetes at the start of the study and at the time of follow-up. Starting from the very beginning of the study and continuing until the end, there was a consistent and maintained reduction in the new diagnosis of diabetes in the treatment arm relative to the placebo arm. To the researchers, this finding suggests that rampiril may prevent diabetes from occurring in the first place. A paper is being prepared which examines this prospect in greater detail.
Gerstein HC. Diabetes and the HOPE study: implications for and disease. Int J Clin Pract Suppl. 2001;117:8-12.
The above summary is adapted from the cited reference.
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