TY - JOUR
T1 - Olmesartan for the Delay or Prevention of Microalbuminuria in Type 2 Diabetes
AU - Haller, Hermann
AU - Ito, Sadayoshi
AU - Izzo, Joseph L.
AU - Januszewicz, Andrzej
AU - Katayama, Shigehiro
AU - Menne, Jan
AU - Mimran, Albert
AU - Rabelink, Ton J.
AU - Ritz, Eberhard
AU - Ruilope, Luis M.
AU - Rump, Lars C.
AU - Viberti, Giancarlo
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
M3 - Article
SN - 1533-4406
VL - 364
SP - 907
EP - 917
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 10
ER -