Objective: Circulating adhesion molecules may have a prognostic significance as markers of endothelial damage. Drugs which inhibit the renin-angiotensin system may be effective in reducing circulating or tissue adhesion molecules, albeit data available are scarce. The aim of the study was to investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor, enalapril and a highly selective angiotensin receptor blocker, candesartan cilexetil, on circulating adhesion molecules in a large sample of patients with non-insulin-dependent diabetes mellitus (NIDDM). The study was comparative, multicenter, randomized and double blind, with two parallel groups.
Patients and methods: NIDDM patients with a diagnosis of mild (grade 1) essential hypertension were included in the study, at the end of a 2-week placebo run-in period. The primary end-point of the study was to evaluate changes of intercellular adhesion molecule-1 (ICAM-1) plasma levels during treatment. The secondary end-points were: changes in vascular cells adhesion molecule-1 (VCAM-1), von Willebrand factor (vWF), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) circulating levels and of urinary albumin excretion rate (AER) as well; 129 patients were randomized: 66 in the candesartan group and 63 in the enalapril group, 118 of them completed the scheduled 24-week treatment period.
Results: Candesartan and enalapril equally reduced circulating level of ICAM-1 and exerted comparable effects on changes of other adhesion molecules and coagulation factors. A similar blood pressure-lowering effect was observed with the two drugs (candesartan: from 148/90 +/- 11/8 to 132/82 +/- 12/7 mmHg, P < 0.01, enalapril: from 148/91 +/- 12/8 to 131/85 +/- 14/6 mmHg, P < 0.01). Candesartan was more effective than enalapril in the reduction of albuminuria (P < 0.05 between treatments), although urinary protein excretion can be considered normal in the majority of patients. The two drugs were comparable in terms of adverse events reported.
Conclusion: Candesartan and enalapril showed similar effects on blood pressure and on circulating adhesion molecules. In this study urinary protein excretion was reduced more by candesartan.