Issue 141 Item 3 Study Verifies 50% Reduction in CVD and Microvascular Events wi

Patients given an ACE inhibitor or angiotensin II-receptor antagonist, regardless of blood pressure, a aspirin 150 mg q.d. and a vitamin-mineral supplement that included chrome picolinate. Long-term intensified interventions focused on multiple risk factors in patients with type 2 diabetes and microalbuminuria can reduce cardiovascular and microvascular events by about half over an 8-year period, Danish physicians report in The New England Journal of Medicine for January 30.

Dr. Oluf Pedersen of Aarhus University and associates point out that recent guidelines from the American Diabetes Association and other national guidelines recommend intensified multifactorial treatment for type 2 diabetes. However, "the effect of this approach has not been confirmed in long-term studies," they write.

In the Steno-2 Study, the investigators enrolled 160 diabetic patients with persistent microalbuminuria. Eighty patients were randomly assigned to conventional treatment, 73 of whom completed the study that ended in December 2001. The other 80 were assigned to the intensive treatment arm of the study, and 67 of these subjects completed the trial.

In the intensive treatment arm, all patients were given an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin II-receptor antagonist, regardless of blood pressure, as well as aspirin 150 mg q.d. and a vitamin-mineral supplement that included chrome picolinate. Patients were advised to consume less than 30% of calories as fat, and less than 10% as saturated fat. Light-to-moderate exercise for a minimum of 30 minutes per day, three to five times as week, along with smoking cessation, were also recommended.

In the intensive treatment arm, pharmacologic treatment was added as necessary to maintain blood pressure below 140/85 before 2000 and 130/80 thereafter. Target total cholesterol was <190 and <175 mg/dL before and after 2000, respectively, and target triglycerides levels were <150mg/dL. Pharmaceutical interventions were initiated in the control subjects after higher values were reached.

After a mean follow-up of 7.8 years, the two groups did not differ significantly in changes in body mass index, smoking cessation, or total energy intake. Nor did serum HDL cholesterol levels, urinary sodium excretion and glomerular filtration differ significantly.

However, measures of hyperglycemia, hypertension, lipid profiles, and urinary albumin excretion had all decreased significantly more in the intensive treatment group than in the control arm. Fat intake was also significantly decreased in the intensive treatment group.

There were 85 cardiovascular events during follow-up in the conventional treatment group versus 33 among the intensive-therapy group. The hazard ratio among the intensive treatment group for cardiovascular disease was 0.47; for nephropathy, 0.39; retinopathy, 0.42; and autonomic neuropathy, 0.37, compared with the conventional therapy group.

"The continued divergence in the rates of the primary end point suggests that therapy for even longer periods may result in an even better prognosis," Dr. Pedersen’s team writes.

In a Journal editorial, Dr. Caren G. Solomon recommends treatment with ACE inhibitors for diabetics who have at least one other cardiovascular risk factor, even in the absence of hypertension and microalbuminuria. "A reasonable conclusion is that targeting associated risk factors is much more likely to be cardioprotective than controlling the glucose level," she maintains. N Engl J Med 2003;348:383-393,457-459