PREVENTION OF MICROALBUMINURIA IN TYPE 2 DIABETES (ROADMAP TRIAL): 6A.02

Abstract

Background: Microalbuminuria is an early sign of diabetic nephropathy and increased cardiovascular risk. We investigated whether early treatment with an angiotensin receptor blocker (ARB) in diabetic subjects with normal albumin excretion delays the occurrence of microalbuminuria and concomitantly recorded cardiovascular and renal events. Methods: We studied 4,447 patients with type 2 diabetes and at least one additional cardiovascular risk factor in a randomized, double-blind, multicentre, controlled, and event-driven (onset of microalbuminuria) trial. They received either 40 mg olmesartan or placebo once daily for a median duration of 3.2 years. In both groups, additional antihypertensive drug treatment (except ACE inhibitors or ARBs) was used to reach the target blood pressure of <130/80 mmHg. Results: Baseline eGFR, blood pressure and cardiovascular disease (CVD) risk profiles were comparable in both groups. Nearly 80% of the subjects in the olmesartan group and 71% in the placebo group achieved target blood pressure at month 48. Kaplan-Meier analysis showed a cumulative incidence of microalbuminuria of 8.2% (n = 178) with olmesartan and 9.8% (n = 210) with placebo which represents a risk reduction of 23% (HR: 0.77; 95.1% CI: 0.63 to 0.94; p = 0.01) in favour of subjects receiving olmesartan. At study end eGFR was lower in the olmesartan-treated subjects (80.1 vs. 83.7 mL/min/1.73 m2, p < 0.001). In both groups 23 subjects had a doubling of the baseline serum creatinine. Overall cardiovascular morbidity and mortality rate was low and similar between groups with cardiovascular morbidity events in 81 (3.6%) and 91 (4.1%) patients, and total mortality in 26 (1.2%) and 15 (1.7%) on olmesartan and placebo, respectively (p > 0.1). Cardiovascular mortality however was higher (15 (0.7%) vs. 3 (0.1%); p = 0.01) in the olmesartan group, possibly due to hypotensive episodes in subjects with pre-existing CVD. Conclusions: In subjects with type 2 diabetes and excellent blood pressure control early treatment with the ARB olmesartan showed a significant risk reduction regarding the ‘time to onset of microalbuminuria’.