Effects of up-titration of candesartan versus candesartan plus amlodipine on kidney function in type 2 diabetic patients with albuminuria

Abstract

In the present study, we tested the hypothesis that uptitrating the dose of an angiotensin receptor blocker (ARB) is superior to combined treatment with an ARB and a calcium channel blocker for the same degree of blood pressure (BP) reduction, with respect to urinary albumin excretion in diabetic patients treated with a standard dose of the ARB. Hypertensive patients with type 2 diabetes mellitus and albuminuria (X30 mg g À1 creatinine) were enroled in the study, and were either started on or switched to candesartan (8 mg per day) monotherapy. After a 12-week run-in period, baseline evaluations were performed and patients with BP X130/80 mm Hg were randomly assigned to receive either candesartan (12 mg per day) or candesartan (8 mg per day) plus amlodipine (2.5 mg per day) for a further 12 weeks. The primary endpoint was a reduction in urinary albumin levels. Although there was no significant difference in the BP reduction between the two groups, the reduction in urinary albumin was greater in the up-titrated than the combination therapy group (À40 ± 14% vs À9 ± 38%, respectively; Po0.0001). Thus, up-titration of candesartan more effectively reduces urinary albumin excretion than combined candesartan plus amlodipine in hypertensive patients with diabetes for the same degree of BP reduction.

Are Large Sample Size Studies the Answer to Evaluate Effects of Drug Use in Non–Clinical Trial Settings?

“…On the other hand, a large sample size study without proper design and data analysis, as well as factors for calculation of the propensity score and important cancer risk factors such as body mass index, HbA 1c and lipids, which can be associated with cancer risk in a nonlinear way, 4,5 for adjustment in the conditional logistic regression analysis might result in significant but false associations between drug use and cancer. A small sample size study with adequate design and adjustment for all possible confounding factors may yield nonsignificant but numerically correct results.…”

“…2 The use of blockers of the renin-angiotensin system to treat these conditions, as investigated in the article authored by Chang et al 3 published recently in Journal of Clinical Oncology, has attracted considerable attention as well. Blockade of the production of angiotensin II (AngII) by angiotensin converting enzyme inhibitors or antagonists of the angiotensin type 1 receptor improves the pathology and decreases organ damage in diabetes [4][5][6] and cancer. They conclude that the "underlying mechanism certainly requires further investigation."…”