Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes

BACKGROUND: Microalbuminuria is an early predictor of diabetic nephropathy and
premature cardiovascular disease. We investigated whether treatment with an
angiotensin-receptor blocker (ARB) would delay or prevent the occurrence of
microalbuminuria in patients with type 2 diabetes and normoalbuminuria. METHODS:
In a randomized, double-blind, multicenter, controlled trial, we assigned 4447
patients with type 2 diabetes to receive olmesartan (at a dose of 40 mg once
daily) or placebo for a median of 3.2 years. Additional antihypertensive drugs
(except angiotensin-converting-enzyme inhibitors or ARBs) were used as needed to
lower blood pressure to less than 130/80 mm Hg. The primary outcome was the time
to the first onset of microalbuminuria. The times to the onset of renal and
cardiovascular events were analyzed as secondary end points. RESULTS: The target
blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the patients taking
olmesartan and 71% taking placebo; blood pressure measured in the clinic was
lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group.
Microalbuminuria developed in 8.2% of the patients in the olmesartan group (178
of 2160 patients who could be evaluated) and 9.8% in the placebo group (210 of
2139); the time to the onset of microalbuminuria was increased by 23% with
olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence
interval, 0.63 to 0.94; P=0.01). The serum creatinine level doubled in 1% of the
patients in each group. Slightly fewer patients in the olmesartan group than in
the placebo group had nonfatal cardiovascular events--81 of 2232 patients (3.6%)
as compared with 91 of 2215 patients (4.1%) (P=0.37)--but a greater number had
fatal cardiovascular events--15 patients (0.7%) as compared with 3 patients
(0.1%) (P=0.01), a difference that was attributable in part to a higher rate of
death from cardiovascular causes in the olmesartan group than in the placebo
group among patients with preexisting coronary heart disease (11 of 564 patients
[2.0%] vs. 1 of 540 [0.2%], P=0.02). CONCLUSIONS: Olmesartan was associated with
a delayed onset of microalbuminuria, even though blood-pressure control in both
groups was excellent according to current standards. The higher rate of fatal
cardiovascular events with olmesartan among patients with preexisting coronary
heart disease is of concern. (Funded by Daiichi Sankyo; ClinicalTrials.gov
number, NCT00185159.).