AMADEO: Telmisartan demonstrates greater reductions in urinary protein levels than losartan

Key Points

In a randomized, controlled trial, telmisartan demonstrated a greater antiproteinuric effect than losartan in hypertensive patients with type 2 diabetes and chronic kidney disease. The drugs demonstrated similar levels of blood pressure control.

Telmisartan is currently approved for the treatment of hypertension but is not indicated for the treatment of proteinuria in patients with diabetes. Losartan is currently approved as a first-line treatment for diabetic nephropathy.

The results of the Efficacy of Telmisartan Compared with Losartan in Reducing Proteinuria in Hypertensive Type 2 Diabetic Patients with Overt Nephropathy (AMADEO) trial were presented at the American Society of Hypertension 22nd Annual Scientific Meeting and Exposition from May 19 to May 22, 2007, in Chicago, Illinois.

"What is newly appreciated is that it's not good enough to just lower blood pressure," Dr Bakris said. "We have to see what's happening to albuminuria. Albumin is an even better predictor of outcomes than proteinuria in terms of both kidney disease and cardiovascular disease."

Several previous trials have demonstrated that in patients with diabetic nephropathy, control of blood pressure with an agent that inhibits the renin-angiotensin system slows progression of renal disease. These trials demonstrated that a >30% reduction in proteinuria at 6 months to 1 year following initiation of treatment was associated with slowed progression of diabetic nephropathy and a reduction in the incidence of cardiovascular events, independent of reductions in blood pressures.

Current National Heart Lung and Blood Institute (NHLBI) guidelines for the treatment of hypertension recommend the use of angiotensin receptor blockers (ARBs) for the treatment of diabetic nephropathy in order to slow the progression of kidney disease.

Patients in the study had diabetes for an average of 14 to 16 years.

"If you were to look at estimated glomerular filtration rate, they had lost about 60% to 65% of their kidney function. This is well-advanced kidney disease that would be considered advanced stage 3 nephropathy," Dr Bakris said.

After 1 year of treatment, patients were followed for an additional 8 weeks to determine the persistent effect of the agents on urinary protein excretion independent of blood pressure reduction.

Blood pressure reductions between the groups were not significantly different; however, despite this lack of a difference, the mean final urinary protein to creatinine ratio was significantly lower among the telmisartan-treated patients than among the losartan-treated patients (0.71 vs 0.80; P=.0284).

In addition, Dr Bakris said that: "A greater percentage of people had sustained persistent antiproteinuric effects following 2 months of telmisartan discontinuation."

There was no significant difference between groups in urinary sodium to creatinine ratio, glomerular filtration rate, serum aldosterone, or high-sensitivity C-reactive protein levels.

Dr Bakris said that the advantage of telmisartan in this study may lie in pharmacologic differences between telmisartan and losartan (ie, telmisartan has a longer duration of action and its magnitude of binding to the angiotensin-1 receptor is greater).

SOURCE

The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure (JNC 7). National Heart Lung and Blood Institute website. 2003. http:// http://www.nhlbi.nih.gov/guidelines/hypertension/index.htm. Accessed June 13, 2007.