Multifactorial Intervention and
Cardiovascular Disease in Patients
with Type 2 Diabetes

Patients with diabetes are at substantially increased risk of cardiovascular disease (CVD)—particularly those with multiple modifiable risk factors for late diabetic complications. Those risk factors include hyperglycemia, hypertension, and dyslipidemia. Intensified interventions targeted at single risk factors have demonstrated benefits in terms of both microvascular and macrovascular complications in patients with type 2 diabetes. Thus, guidelines issued by the American Diabetes Association, as well as other national organizations, recommend intensified multifactorial treatment for the management of type 2 diabetes; however, long-term studies on the benefits of this multifactorial approach have been lacking.

The Steno-2 Study, a randomized, open, parallel trial, compares the effect of a targeted, intensified, multifactorial intervention (n=80) with that of conventional treatment (n=80) on risk factors for CVD in patients with type 2 diabetes and microalbuminuria. Conventional treatment by general practitioners was based on the 1988 guidelines of the Danish Medical Association; the multifactorial intervention involved a stepwise implementation of behavior modification and pharmacologic therapy with strict treatment goals, targeting hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, as well as aspirin for secondary prevention of cardiovascular disease. Project teams at the Steno Diabetes Center oversaw the intervention. The primary end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization, and amputation; secondary end points were indicators of microvascular disease (diabetic nephropathy, retinopathy, or neuropathy).

After a mean follow-up of 7.8 years, the intensive-therapy group showed significantly greater declines in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels, and urinary albumin excretion rates compared with the conventional-therapy group. The intensified multifactorial treatment significantly reduced the risk of CVD (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.24–0.73). Cardiovascular events occurred in 24% of patients in the intensive-therapy group and in 44% of patients in the conventional-therapy group. In addition, patients receiving intensified therapy had significantly lower risks of nephropathy (HR, 0.39; 95% CI, 0.17–0.87), retinopathy (HR, 0.42; 0.21–0.86), and autonomic neuropathy (HR, 0.37; 0.18–0.79).

Thus, a long-term, target-driven, multifactorial intensified intervention in patients with type 2 diabetes and microalbuminuria reduced the risk of cardiovascular and microvascular events by approximately 50%. While previous studies demonstrated the benefits of individual components of this approach, this study provides the best evidence to date of the magnitude of the treatment effect that multifactorial interventions can achieve. This study suggests that five patients need to be intensively treated for this length of time to prevent one cardiovascular event. The authors concluded that an approach such as this should be offered to patients with type 2 diabetes and microalbuminuria to reduce the risks for both macrovascular and microvascular complications.

New England Journal of Medicine

Peter Gaede, MD, Pernille Vedel, MD, PhD, Nicolai Larsen MD, PhD, Gunnar V. H. Jensen, MD, PhD, Hans-Henrik Parving, MD, DMSc, Oluf Pedersen, MD, DMSc