Megadosage Candesartan Beneficial
Renal disease patients who have persistent proteinuria despite treatment with the highest approved dosage of the angiotensin receptor blocker candesartan may benefit from higher dosages, a Canadian study finds.
A team led by Ellen Burgess, MD, of the University of Calgary in Alberta, studied 269 patients with persistent proteinuria (1 g/day or greater) despite seven weeks of treatment with the highest dosage of candesartan (16 mg/day) approved in Canada.
The researchers randomly assigned patients to receive 16, 64, or 128 mg/day of candesartan for 30 weeks. Subjects had a median serum creatinine level of 1.47 mg/dL and median urinary protein excretion of 2.66 g/day. Fifty-four percent had diabetic nephropathy.
Compared with the 16 mg/day group, the 128 mg/day recipients had a mean 33% decrease in proteinuria, Dr. Burgess and colleagues reported in the Journal of the American Society of Nephrology (2009;20:893-900). The three treatment arms had similar reductions in BP. Elevated potassium levels led to the early withdrawal of 11 patients, but the investigators observed no dosage-related increases in adverse events.
The most frequent adverse events were peripheral edema, headache, fatigue, and nasopharyngitis, the investigators reported. The rate of peripheral edema appeared to decline as the candesartan dosage increased. It occurred in 22.2%, 18.9%, and 12.4% of patients in the 16, 64, and 128 mg/day groups, respectively.