Lancet: Dual angiotensin blockade may harm kidneys

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In people at high vascular risk, the combination of ramipril and telmisartan worsens major renal outcomes overall despite a reduction in proteinuria as a monotherapy, according to the ON-TARGET trial published in the Aug. 19 cardiology special issue of The Lancet.

Johannes FE Mann, MD, from the Ludwig Maximilian University in Munich, Germany, and colleagues sought to investigate the renal effects of ACE inhibitor ramipril (Altace from Wyeth and Monarch Pharmaceuticals), the angiotensin receptor blocker (ARB) telmisartan (Micardis from Boehringer-Ingelheim) and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. The trial ran from 2001 to 2007.

Researchers randomly assigned 25,620 participants to either the ACE, ARB or both. The primary renal outcome was a composite of dialysis, doubling of serum creatinine and death.

The researchers said that 784 patients permanently discontinued randomized therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril and 229 on telmisartan).

Mann and colleagues found that the number of events for the composite primary outcome was similar for telmisartan (1,147 patients) and ramipril (1,150 patients; but was increased with combination therapy (1,233 patients).

The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 patients) and ramipril (174 patients) and more frequent with combination therapy (212), the authors wrote.

Estimated glomerular filtration rate declined least with ramipril compared with telmisartan or combination therapy, according to the investigators. They also found an increase in urinary albumin excretion was less with telmisartan or with combination therapy than with ramipril.

Based on their findings, Mann and colleagues wrote that “even considering acute and chronic renal failure separately, there was no evidence for a renal benefit with combination therapy even though proteinuria was reduced.”

The authors wrote that “although ONTARGET was not specifically powered to detect differences of major renal outcomes, nearly 3,500 primary renal events were recorded.”

However, they also noted that “why clinical renal adverse events were seen more frequently with combination therapy than with ramipril is unclear.”