BACKGROUND: Observational studies suggest a synergistic effect of hypertension and hyperlipidaemia on the progression of atherosclerosis. The alpha-blocker doxazosin has favourable effects on plasma lipids, insulin resistance and blood pressure, while the diuretic hydrochlorothiazide (HCTZ) principally affects blood pressure and increases insulin resistance. METHODS: A randomised double-blind study over 36 months was performed to compare the effects of doxazosin and HCTZ on fasting lipids and on progression of peripheral atherosclerosis. Eighty males (45 to 70 years) with peripheral atherosclerotic disease and increased cholesterol levels (5.2-8.0 mmol/l) were treated for essential hypertension with either doxazosin (n = 41) or HCTZ (n = 39). Main outcome measures were arterial intima-media thickness (IMT) of the carotid and femoral arteries and fasting lipid parameters. RESULTS: In the doxazosin-treated group, significant changes were observed in the concentration of triglycerides (-13.7%, p < 0.01), HDLc (+25.7%, p < 0.05) and IDLc (-30.1%, P < 0.05). In the HCTZ-treated group no significant changes in plasma lipid levels were observed. On follow-up visits systolic blood pressure in the doxazosin-treated group was 6 mm higher than in the HCTZ group. Nevertheless, the groups treated with doxazosin or HCTZ showed no differential effect on IMT after three years of treatment (p = 0.8). A significant reduction of the IMT of combined carotid and femoral arterial walls was shown in both treatment groups (p < 0.005). CONCLUSIONS: Hypertension treatment with doxazosin or HCTZ resulted in a comparable change in arterial IMT after three years, in spite of differences in effect on plasma lipids. The study emphasises the importance of blood pressure control in patients with peripheral vascular disease and hypercholesterolaemia.

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The Netherlands Journal of Medicine
Erasmus MC: University Medical Center Rotterdam

Hoogerbrugge, N., de Groot, E., de Heide, L. H. M., de Ridder, M., Birkenhäger, J., Stijnen, T., & Jansen, H. (2002). Doxazosin and hydrochlorothiazide equally affect arterial wall thickness in hypertensive males with hypercholesterolaemia (the DAPHNE study) Doxazosin Atherosclerosis Progression Study in Hypertensives in the Netherlands. The Netherlands Journal of Medicine. Retrieved from