Less microalbuminuria but more CV deaths with olmesartan

The angiotensin-receptor blocker (ARB) olmesartan delayed diabetic patients' development of microalbuminuria compared to placebo, a new trial found.

The manufacturer-sponsored, randomized trial assigned more than 4,000 patients with type 2 diabetes to either 40 mg of olmesartan per day or placebo for a median of 3.2 years. Patients also took other antihypertensive drugs (except angiotensin-converting enzyme inhibitors or ARBs) as needed to achieve a target blood pressure of less than 130/80 mm Hg. Overall, the target was achieved in more than 70% of patients. The results were published in the March 10 New England Journal of Medicine.

Blood pressure in the olmesartan group was lower than in the placebo group by 3.1/1.9 mm Hg. The intervention group also fared better on the study's primary outcome—time to microalbuminuria—with a 23% longer time to onset (P=0.01). Intervention patients also had lower overall rates of microalbuminuria (8.2% vs. 9.8%). The greatest benefits were seen in patients who had higher systolic blood pressure at baseline, better control of diabetes, lower renal function and a urinary albumin-to-creatinine ratio of more than 4. Other recent studies support the finding that higher baseline blood pressure is associated with more benefit from an ARB or angiotensin-converting enzyme inhibitor, the authors noted.

Secondary end points of the study included renal and cardiovascular events. The overall rate of these events was low (about 4%), but one concerning finding was the greater number of deaths from cardiovascular causes in the olmesartan group (15 patients vs. 3, P=0.01). The finding could be due to chance, study authors cautioned, but they also noted that a similar finding from another olmesartan trial (ORIENT) has led the FDA to initiate a review of the drug's safety. In the current study, the increase in cardiovascular deaths appeared to be due to differences in patients with preexisting coronary heart disease, and it was strongest among those with the highest or lowest blood pressures, consistent with the “J-curve effect.”

The study's findings provide hope that it is possible to prevent progression to chronic kidney disease in type 2 diabetics, concluded an accompanying commentary. Physicians will likely be divided about what the results mean for use of olmesartan specifically, with some concluding that the benefits outweigh the possible risks of cardiovascular death and others preferring to prescribe one of the other ARBs that have not been associated with this risk, the commentary author wrote.