Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study

Abstract

Aims/hypothesis: The renal and cardiovascular protective effects of angiotensin receptor blocker (ARB) remain controversial in type 2 diabetic patients treated with a contemporary regimen including an angiotensin converting enzyme inhibitor (ACEI).

Methods: We examined the effects of olmesartan, an ARB, on primary composite outcome of doubling of serum creatinine, endstage renal disease and death in type 2 diabetic patients with overt nephropathy. Secondary outcome included composite cardiovascular outcomes, changes in renal function and proteinuria. Randomisation and allocation to trial group were carried out by a central computer system. Participants, caregivers, the people carrying out examinations and people assessing the outcomes were blinded to group assignment.

Results: Five hundred and seventy-seven (377 Japanese, 200 Chinese) patients treated with antihypertensive therapy (73.5% [n = 424] received concomitant ACEI), were given either once-daily olmesartan (10-40 mg) (n = 288) or placebo (n = 289) over 3.2 ± 0.6 years (mean±SD). In the olmesartan group, 116 developed the primary outcome (41.1%) compared with 129 (45.4%) in the placebo group (HR 0.97, 95% CI 0.75, 1.24; p = 0.791). Olmesartan significantly decreased blood pressure, proteinuria and rate of change of reciprocal serum creatinine. Cardiovascular death was higher in the olmesartan group than the placebo group (ten vs three cases), whereas major adverse cardiovascular events (cardiovascular death plus non-fatal stroke and myocardial infarction) and all-cause death were similar between the two groups (major adverse cardiovascular events 18 vs 21 cases, all-cause deaths; 19 vs 20 cases). Hyperkalaemia was more frequent in the olmesartan group than the placebo group (9.2% vs 5.3%).

Conclusions/interpretation: Olmesartan was well tolerated but did not improve renal outcome on top of ACEI.

Trial registration: ClinicalTrials.gov NCT00141453.

Fig. 1

Kaplan–Meier analysis of the time to primary composite renal endpoint in type 2 diabetic patients with overt proteinuria and renal insufficiency. Solid line, olmesartan; dashed line, placebo

Fig. 2

Kaplan–Meier analysis of the time to secondary composite cardiovascular endpoint in type 2 diabetic patients with overt proteinuria and renal insufficiency. Solid line, olmesartan; dashed line, placebo

Fig. 3

Changes in proteinuria expressed as percentage change of urinary protein/creatinine ratio from baseline during treatment with olmesartan or placebo in type 2 diabetic patients with overt proteinuria and renal insufficiency. Solid line, black circles, olmesartan; dashed line, white circles, placebo. p = 0.005

Fig. 4

Cumulative frequency distribution of yearly rate of change of 1/SCr. The two arrows refer to the median values in the placebo or olmesartan groups. Black circles, olmesartan; white circles, placebo