SAN DIEGO — Olmesartan reduced the risk of microalbuminuria by 23% in normoalbuminuric patients with type 2 diabetes and at least one additional cardiovascular disease risk factor, results from a large European trial showed.
The angiotensin receptor blocker (ARB) also yielded unprecedented blood pressure control for this population.
Those are the first key findings from the Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study, presented at the annual meeting of the American Society of Nephrology.
“Despite all of our efforts, we still have problems effectively treating diabetic nephropathy,” said the study's steering committee chair, Dr. Hermann G. Haller of the department of nephrology at Hannover (Germany) Medical School. “The problem for prevention is that we have to diagnose and treat it early. Microalbuminuria is the first sign of the pathogenesis of diabetic nephropathy. It is also an important marker of early development of cardiovascular disease and can indicate microvascular disease.”
The primary end point of the study was occurrence of microalbuminuria based on two or more positive morning spot urine measurements. Secondary end points were cardiovascular events, renal function, and microvascular morbidity.
With support from Daiichi Sankyo, which markets olmesartan, researchers in 19 countries enrolled 4,449 patients aged 18-75 years with well-controlled type 2 diabetes. All patients were normoalbuminuric (a level of 25 mg/g or less for men, 35 mg/g or less for women) and had at least one additional cardiovascular risk factor such as high triglyceride levels or hypertension. None of the participants had received an ACE inhibitor or an ARB within 6 months of participation.
The patients were randomized to olmesartan 40 mg/day or placebo. The urine albumin creatinine ratio was determined every 6 months. Patients were followed for an average of 3.2 years.
At their discretion, study investigators could add calcium channel blockers, diuretics, or beta-blockers to the regimen to help patients achieve the target blood pressure goal of 130/80 mm Hg.
The patients' mean age was 58 years, mean duration of diabetes was 6 years, mean hemoglobin A1c level was 7.6%, and mean body mass index was 31 kg/m
Dr. Haller reported that nearly 80% of patients in the olmesartan group reached the target BP of 130/80 mm Hg at 42 months, compared with 75% of patients in the placebo group. “The percentage of patients reaching the blood pressure goal was very high,” he said.
Over the study period, microalbuminuria occurred in 8% of the patients in the olmesartan group and 10% of the patients on placebo, a statistically significant difference. This translated into a risk reduction of 23% for the olmesartan group, compared with the placebo group.
After 1 year, the first incidence of microalbuminuria occurred in 3% of patients in both groups. For the remainder of the study, fewer patients in the olmesartan group experienced microalbuminuria, compared with the placebo group. “The divergence after 1 year indicates that the specific effects of olmesartan are not due to early hemodynamic changes that would have happened in the first couple of months,” Dr. Haller said in an interview. “We think that olmesartan has a specific, perhaps structural effect on the kidney, either in the glomeruli or in the basal membrane, in the microcirculation.”
When the researchers assessed the BP effect in the olmesartan group corrected for diastolic and systolic BP, the risk reductions did not reach statistical significance (18% vs. 17%, respectively).
No adverse events from olmesartan were observed on renal outcomes, and the incidence of cardiovascular morbidity and mortality affected fewer than 1% of the entire study population. “Most likely the event rate is very low because of the excellent blood pressure control,” Dr. Haller said.
Some cardiovascular events such as a higher incidence of nonfatal stroke and sudden cardiac death were seen in the olmesartan group, compared with the placebo group, but due to the small number of cases, “we have to analyze this further,” Dr. Haller emphasized. An observational follow-up study is underway to further understand the long-term benefits of microalbuminuria prevention.
Dr. Haller is a paid consultant for Daiichi Sankyo and several other pharmaceutical companies, and has received honoraria from various drug companies.
Microalbuminuria is an important marker of diabetic nephropathy, which must be diagnosed and treated early.
Source DR. HALLER