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Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators.

Lancet. 2000 Jan 22;355(9200):253-9

Article Abstract:

BACKGROUND: 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. METHODS: 3577 people with diabetes included in the Heart Outcomes Prevention Evaluation 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. Overt nephropathy was a main outcome in a substudy. FINDINGS: The study was stopped 6 months early (after 4.5 years) by the independent data safety 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 22% (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). INTERPRETATION: 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.

WHAT IS THE EVIDENCE THAT ANGIOTENSIN INHIBITION PROTECTS THE KIDNEY IN DIABETES?

By: Anonymous - Wed 4/25/2007 PM

From the MICRO HOPE sub-study published in the Lancet, January 22, 2000 there is evidence that Ramipril protects people with diabetes from developing nephropathy. The Heart Outcomes Prevention Evaluation (HOPE) study was a large study to see if the addition of Ramipril 10mg per day to people at high risk of developing a cardiovascular event was beneficial in reducing the incidence of myocardial infarctions, strokes and cardiovascular deaths. The Microalbuminuria Cardiovascular and Renal Outcomes (MICRO) was a substudy of the HOPE patients with diabetes to see the result of Ramipril on overt nephropathy. And these were all people without clinical proteinuria. The results of the MICRO HOPE substudy showed a significant benefit by Ramipril in protecting the kidney and this protective effect appeared to be distinct from the blood pressure lowering effect of Ramipril.

* The RENAAL study published in the New England Journal of Medicine, September 20, 2001 showed the value of Losartan in protecting the kidney of diabetic patients. In this study, patients with type 2 diabetes and evidence of early nephropathy (defined as urine albumin : urine creatinine ratio of 300 or more or elevated serum creatinine) were treated with either Losartan (50 or 100mg per day) or placebo for over 3 years. All of them received appropriate other treatments for hypertension and diabetes. The results showed that Losartan had a significant reno-protective effect.

* The BENEDICT study published in the New England Journal of Medicine, November 4, 2004 studied whether treatment with the ACE inhibitor Trandolapril was useful in preventing microalbuminuria in patients with Type 2 diabetes and hypertension. Trandolapril was compared to Verapamil alone and to the combination of Trandolapril plus Verapamil. The results showed that Trandolapril was useful in protecting the kidney of those with diabetes and hypertension.

* The IDNT study published in the New England Journal of Medicine, September 20, 2001 showed that Irbesartan 300mg per day, offered significant renal protection to patients with hypertension, type 2 diabetes and overt nephropathy. The use of Irbesartan in such patients slowed the doubling of serum creatinine and reduced the speed of progression to end stage renal failure.

Another study called the IRMA study published in the same Journal showed that Irbesartan (150mg or 300mg per day) protected the kidneys of patients with hypertension, type 2 diabetes and incipient nephropathy. Irbesartan in these patients reduced the rate of progression from incipient nephropathy to overt nephropathy.

Early proteinuric diabetic nephropathy increases some chemicals which in turn increases systemic and renal oxidative/nitrosative stress. An ACEI or an ARB prevents these changes and prevents the development of proteinuria, independent of blood pressure or blood sugar. This finding indicates a pathogenic role for AT1 receptors in the development of oxidative damage in the kidneys during early DM. however this was performed on rats with Diabetes. the article is Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: Effects of ACEI and ARB.

Source: http://psgjournalclub.blogspot.com/2007/04/wh...

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