• Diabetes Mellitus
• Renal Disease
• Diabetes & Endocrinology Clinical Trials
• Hypertensive Disease
• Diabetes & Kidney Disease

Preventing the progression of normal albumin excretion to microalbuminuria should be a goal in the management of patients with type 2 diabetes mellitus (T2DM), since microalbuminuria is an early sign of diabetic nephropathy and elevated cardiovascular (CV) risk. The Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention (ROADMAP; NCT00185159) study investigated whether early administration of an angiotensin receptor blocker (ARB) to diabetic patients with normal albumin excretion could delay or prevent the first occurrence of microalbuminuria and whether it could affect the incidence of CV and renal events.

This multinational European trial randomly assigned 4447 patients (aged 18 to 75 years) with T2DM and at least one additional CV risk factor and normoalbuminuria to olmesartan 40 mg (n=2232) or placebo (n=2215). Patients could also receive other antihypertensive medication that did not act on the renin-angiotensin system but could not have been treated with an angiotensin-converting enzyme inhibitor or ARB in the previous 6 months. The groups were well matched at baseline for gender, age (58 years), body mass index (31 kg/m²), glycated hemoglobin (7.65% to 7.66%), duration of diabetes (6.1 to 6.2 years), estimated glomerular filtration rate (85 mL/min/1.73 m²), serum creatinine (77 mmol/L), and systolic (136 to 137 mm Hg) and diastolic (80 to 81 mm Hg) blood pressure (SBP and DBP, respectively).

The median albumin-to-creatinine ratio was higher (4.00 mg/g; 95% CI, 1.0 to 46.8) for the olmesartan group versus the placebo group (3.00 mg/g; 95% CI, 1.0 to 35.0), and the olmesartan group had higher serum triglyceride levels at baseline (2.13 ± 1.70 mmol/L) than the placebo group (2.03 ± 1.28 mmol/L).

Hermann Haller, MD, University of Hannover Medical School, Hannover, Germany, presented data from ROADMAP. Over the 48 months of the study, the olmesartan group achieved a reduction of sitting SBP/DBP of 3.0/1.9 mm Hg compared with the control group. Similarly, more patients in the olmesartan arm reached the blood pressure goal of <130/80 mm Hg than in the placebo arm (78.2% vs 71.3% of patients, respectively). Interestingly, fewer olmesartan patients were at goal at baseline (28%) compared with the placebo group (30%).

At 48 months, more patients in the placebo group had reached the primary endpoint of time to first occurrence of microalbuminuria compared with those who received olmesartan. Olmesartan use was associated with a 23% reduction in risk of reaching this endpoint (HR, 0.770; 95% CI, 0.630 to 0.941; p=0.0104).

Olmesartan was associated with a 19% risk reduction, even after the time to first occurrence of microalbuminuria was corrected for the last mean blood pressure differences (SBP-corrected HR, 0.814; p=0.0451; DBP-corrected HR, 0.810; p=0.0398). However, when the values were corrected for the areas under the blood pressure curves from baseline to last assessment, there was no significant difference between the groups (SBP-corrected HR, 0.834; p=0.0789; DBP-corrected HR, 0.823; p=0.0596).

Olmesartan did not prove to be different from placebo in terms of preventing CV morbidity and mortality, all CV morbidity, or transient ischemic attack and atrial fibrillation. In a post hoc analysis, olmesartan was shown to reduce the risk of cardiac morbidity by 36% (HR,0.64; p=0.03).

Prof. Haller reported that there were 15 deaths in the olmesartan arm compared with 3 in the placebo arm. However, the increased mortality was seen only among patients who had preexisting CV disease (n=1104; p=0.02 between olmesartan and placebo). Furthermore, among such patients, the quartiles with the lowest SBP before the event or the greatest reduction in SBP had the highest CV mortality (eg, in the quartile with SBP <122.3 mm Hg, there was about a 2.5-fold increased incidence of events vs the next highest quartile; SBP 122.3 mm Hg to <126.4 mm Hg).

In summary, olmesartan was associated with a 23% risk reduction and delayed the occurrence of microalbuminuria, with the majority of the effect being independent of blood pressure. Olmesartan was highly efficacious in controlling blood pressure, with nearly 80% of patients reaching goal at 48 months. Prof Haller cautioned that blood pressure reduction below 120/70 mm Hg is not recommended for patients with T2DM and known coronary heart disease.

• © 2010 MD Conference Express