Clinical Question: Do angiotensin-receptor blockers prevent cardiovascular disease in patients with diabetes?

Setting: Outpatient (any)

Study Design: Randomized controlled trial (double-blinded)

Synopsis: The investigators of this multinational study enrolled 1,715 patients with type 2 diabetes and nephropathy, most of whom had hypertension. Allocation to treatment assignment was concealed. The patients had significant proteinuria, averaging 2.9 g of urinary protein per day. Most of the participants had retinopathy, and approximately 30 percent had preexisting heart disease. More than one half of the patients also were receiving insulin.

The patients were assigned to receive placebo, amlodipine in a dosage of 10 mg per day, or irbesartan in a dosage of 300 mg per day. The blood pressure goal was less than 135/85 mm Hg and was controlled using classes of antihypertensive drugs (except angiotensin-converting enzyme inhibitors) other than those represented by the study drugs. Although most patients were taking several antihypertensive drugs during the study (an average of three, in addition to the study medication), the average blood pressure was 140/77 mm Hg in the treated patients.

Overall, approximately 30 percent of the patients experienced a cardiovascular event during the average 2.6 years of follow-up, and the rates were similar in the treatment and placebo groups. The time to the first cardiovascular event did not differ among the three groups. Some differences were noted in individual outcomes: heart failure occurred more often in patients receiving amlodipine than in patients receiving irbesartan or placebo, yet patients receiving this treatment were less likely to experience a myocardial infarction. The lack of a difference may be explained by the aggressive lowering of blood pressure in all three groups, or that most of the patients were receiving insulin to control their blood glucose.

Bottom Line: Neither the angiotensin-receptor blocker irbesartan nor the calcium channel blocker amlodipine, when added to aggressive antihypertensive therapy in patients with type 2 diabetes, decreases the likelihood of patients experiencing a cardiovascular event. (Level of Evidence: 1c)