Comparative cross-over study of the effects of lisinopril and doxazosin on insulin, glucose and lipoprotein metabolism and the endogenous fibrinolytic system

Summary Objective: The present study was performed to compare the effects of the alpha-1-blocker doxazosin (4 mg/d) with the ACE-inhibitor lisinopril (10 mg/d) in a cross-over study on plasma levels of metabolic and fibrinolytic parameters. Patients, methods: In 10 male patients with upper body obesity, proven stable coronary artery disease and hypertension, measurements included baseline determination of lipoproteins and fibrinolytic parameters and determinations of glucose and insulin during intravenous glucose tolerance tests after two 12-week treatment periods. Results: Basal insulin levels were significantly decreased by both doxazosin and lisinopril (from 15.5±3.5 μU/ml to 11.6±2 μU/ml, P ≤0.05 and from 16.5±2.8 μU/ml to 11.2±2.4 μU/ml, P ≤0.001; respectively). Lisinopril decreased the area under the insulin-concentration time curve by 31.9% ( P ≤0.007) as compared to 23.6% (n.s.) after doxazosin treatment. HDL-cholesterol was increased by lisinopril from 38±3.5 to 43.5±4.4 mg/dl ( P ≤0.05), t-PA antigen was increased by doxazosin from 8.3±0.7 to 11.4±1.6 ng/ml ( P ≤0.05) and PAI-1 was not affected by either therapy. Conclusion: These potentially favorable effects on insulin and lipid metabolism and the endogenous fibrinolytic system might contribute to a higher efficacy of antihypertensive treatment in patients with coronary artery disease and accompanying metabolic cardiovascular risk factors.