• Research Review
• Journal Review

Title: Multifactorial Intervention and Cardiovascular Disease in Patients with Type 2 Diabetes

Authors: Peter Gæde, Pernille Vedel, et al.

Reviewer: Carlos Mendoza Montano Ph.D. APRECOR, Guatemala

Reference: N Engl J Med (2003); 348:383-393

Problem addressed: Multiple modifiable risk factors for late complications in patients with type 2 diabetes, including hyperglycemia, hypertension, and dyslipidemia, increase the risk of a poor outcome. Randomized trials that investigated the effect of intensified intervention involving a single risk factor in patients with type 2 diabetes demonstrated benefits in terms of both macrovascular and microvascular complications in kidneys, eyes, and nerves. On the basis of the results of these trials, recent guidelines from the American Diabetes Association and other national guidelines recommend an intensified multifactorial treatment approach, although the effect of this approach has not been confirmed in long-term studies.

Purpose of study: To evaluate the effect on cardiovascular disease of an intensified, targeted, multifactorial intervention comprising behavior modification and polypharmacologic therapy aimed at several modifiable risk factors in patients with type 2 diabetes and microalbuminuria

Location of the study: Denmark.

Study design: The primary end point of this trial was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization, and amputation. Eighty patients were randomly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment, with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin. The intensive treatment included a dietary intervention which aimed a total daily intake of fat that was less than 30 percent of the daily energy intake and an intake of saturated fatty acids that was less than 10 percent of the daily energy intake. Light-to-moderate exercise for at least 30 minutes three to five times weekly was recommended, and all smoking patients and their spouses were invited to participate in smoking-cessation courses. All patients were prescribed an angiotensin-converting-enzyme (ACE) inhibitor or, if such a drug was contraindicated, an angiotensin II-receptor antagonist irrespective of the blood pressure level. They also received a daily vitamin-mineral supplement containing vitamin C, vitamin E, folic acid, and chrome picolinate. Initially, 150 mg of aspirin per day was given as secondary prevention to patients with a history of ischemic cardiovascular disease, and after October 1999, all patients received aspirin

Results: The mean age of the patients was 55.1 years, and the mean follow-up was 7.8 years. The decline in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels measured after an overnight fast, and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group. Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease (hazard ratio, 0.47; 95 percent confidence interval, 0.24 to 0.73), nephropathy (hazard ratio, 0.39; 95 percent confidence interval, 0.17 to 0.87), retinopathy (hazard ratio, 0.42; 95 percent confidence interval, 0.21 to 0.86), and autonomic neuropathy (hazard ratio, 0.37; 95 percent confidence interval, 0.18 to 0.79).

Comments: This study clearly demonstrates that a multifactorial strategy reduces the risk of cardiovascular disease among patients with type 2 diabetes. As the authors acknowledge, the design of their study did not allow them to identify which intervention or combination of interventions was responsible for the benefits, or to what extent. Certainly, there is good justification for aggressive treatment of elevated lipid levels and blood pressure in diabetic patients with these risk factors and for the use of aspirin in those with cardiovascular disease or other cardiovascular risk factors. But is there evidence to support the other interventions? Despite the benefits of a multifactorial strategy, making it routine practice is not easy. Interventions similar to those implemented in this study are currently recommended but are underused for several reasons. They require education and time on the part of physicians. In addition, patients must be willing to follow a schedule of regular office visits and blood tests and often to take multiple medications. Although it is difficult to achieve the targets in the real world, the results of this trial suggest the possibility of grate benefits if the targets can be met. In conclusion, for patients who already have diabetes or in whom it will develop, the advantages of a multifactorial approach to the reduction of cardiovascular risk are clear. The challenge is to ensure that this approach is widely adopted.

Citations:

1.Gu K, Cowie CC, Harris MI. Diabetes and decline in heart disease mortality in US adults. JAMA 1999; 281: 1291-1297.
2.Gæde P, Vedel P, Parving HH, Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Lancet 1999;353:617-622