CHICAGO — Telmisartan provides greater reduction in proteinuria than losartan does after 1 year of treatment in patients with hypertension and diabetic nephropathy, Dr. George Bakris said at the annual meeting of the American Society of Hypertension.
This difference can't be attributed to differences in blood pressure control, because blood pressure reductions were comparable in patients taking either angiotension II receptor blocker (ARB), Dr. Bakris, lead investigator of the AMADEO study, said during a press briefing.
After stopping the drugs for 2 months, as per protocol, about twice as many patients on telmisartan were reported to have experienced a slightly greater antiproteinuric effect, compared with those on losartan. This is important to both the Food and Drug Administration and clinicians, because it suggests that telmisartan has done something independent of controlling blood pressure to change the natural history or biology of the disease, said Dr. Bakris.
“The differences between these ARBs in terms of receptor binding, lipophilicity, and duration of action may be responsible for the differences in the effects that you see,” said Dr. Bakris, professor of medicine and director of the hypertension unit at the University of Chicago. “These data suggest that at similar levels of blood pressure control, the longer-acting, higher-binding telmisartan may confer relatively greater protection against the development of ESRD [end-stage renal disease], though that hypothesis must be tested prospectively.”
Dr. Bakris and associates randomized 860 patients with type 2 diabetes mellitus, hypertension (defined as blood pressure greater than 130/80 mm Hg), and overt nephropathy to either telmisartan 40 mg or losartan 50 mg for 2 weeks, and then titrated to 80 mg and 100 mg, respectively. If blood pressure was not controlled, concomitant antihypertensives were allowed, except ARBs, angiotensin-converting enzyme inhibitors, and direct vasodilators.
At admission, the average systolic/diastolic blood pressure was 143/80 mm Hg in both groups; mean urinary protein:creatinine ratio was 1,971 mg/gCr in the telmisartan group vs. 2,010.5 mg/gCr in the losartan group; and the mean serum creatinine was 1.54 mg/dL in the telmisartan group vs. 1.55 mg/dL in the losartan group. In all, 827 patients were available for analysis.
After 1 year of treatment, the mean change in morning spot urinary protein:creatinine—the study's primary end point—was 0.71 for telmisartan and 0.80 for losartan. This translated to a 29% reduction from baseline for telmisartan and a 20% reduction for losartan. Systolic and diastolic BP reductions were not significant between groups (−4.8/−3.2 mm Hg vs. −2.7/–2.9 mm Hg, respectively).
Among secondary end points, telmisartan produced superior reductions in urinary albumin:creatinine and prolonged the time to first cardiovascular event. There were no significant differences between the drugs in urinary sodium:creatinine, glomerular filtration rate, serum aldosterone, or high-sensitivity C-reactive protein. Adverse events were not different between groups.
Dr. Bakris disclosed that he is a consultant and speaker for Boehringer Ingelheim, which sponsored the study, and he has received research support from the firm.
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