The Pharmaceutical Journal
Vol 270 No 7232 p71
18 January 2003

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The Lancet (www.thelancet.com)

Drug combination more effective in renal disease

Progression of renal disease in patients without diabetes is slowed more effectively by using a combination of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin-II receptor blocker rather than by using each drug alone, according to Japanese researchers.

Dr Naoyuki Nakao, of the Showa University, Fujigaoka, and colleagues wanted to see whether management of progressive non-diabetic renal disease would benefit from complete inhibition of the renin-angiotensin-aldosterone system. They therefore randomised 263 patients to one of three treatments — monotherapy with trandolapril (Gopten/Odrik), monotherapy with losartan (Cozaar) or a combination of these drugs — to test the efficacy of each regimen on renal survival.

After three years the trial was stopped early because of a significant difference in survival seen among the three groups. At this time, 11 per cent of patients in the combination group had reached the primary endpoint of time to doubling of serum creatinine concentration or end-stage renal disease compared with 23 per cent in the angiotensin-II receptor blocker group (hazard ratio 0.40, 95 per cent confidence interval 0.17–0.69, P=0.016) and 23 per cent in the ACE inhibitor group (0.38, 0.18–0.63, P=0.018).

The researchers comment that the most striking difference in the groups was the antiproteinuric effect of combination treatment and suggest that the three-year renal survival rate reported for patients in this group is mainly attributable to this effect (Lancet 2003;361:117).