title: Selective alpha 1 inhibition with doxazosin in hypertensive smokers and non-smokers: haemodynamic and metabolic effects.
abstract: Hypertensive cigarette smokers have an especially high risk of coronary heart disease. Doxazosin, which has beneficial effects on haemodynamic factors and lipid metabolism, may be suitable for treating these patients. The haemodynamic and metabolic effects of doxazosin were investigated in a 16-week open, parallel, comparative study of 64 heavy cigarette smokers and 69 non-smokers after a 4-week placebo period. Of the 133 patients who entered, six patients (one smoker and five non-smokers) withdrew due to adverse events. Doxazosin significantly reduced blood pressure without reflex tachycardia in both the smokers and the non-smokers. The therapeutic success rates (reduction in sitting diastolic blood pressure to less than or equal to 90 mmHg and greater than or equal to 5 mmHg reduction, or greater than or equal to 10 mmHg reduction from baseline) were similar for the smokers (93.3%) and the non-smokers (92.5%). Doxazosin significantly decreased total cholesterol and low-density lipoprotein (LDL) cholesterol, but increased high-density lipoprotein (HDL) cholesterol and the HDL:total cholesterol ratio in both smokers and non-smokers. Doxazosin corrected the reduction in HDL cholesterol caused by smoking; compared with baseline, doxazosin increased HDL cholesterol by 19% in hypertensive smokers. The beneficial effects of doxazosin on blood pressure and the lipid profile were apparent in the change in the 10-year probability of developing coronary heart disease as calculated by the Framingham equation; the calculated risk of coronary heart disease decreased by 39% in smokers and by 33% in non-smokers. Plasma fibrinogen and plasminogen activator inhibitor, which independently contribute to atherosclerosis, were significantly reduced by doxazosin in the non-smokers but not in the smokers.
authors.affiliation: Department of Internal Medicine, Ullevaal University Hospital, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Westheim
authors.forename: L N
authors.initials: LN
authors.lastname: Daae
authors.forename: P
authors.initials: P
authors.lastname: Kierulf
authors.forename: B
authors.initials: B
authors.lastname: Brusletto
authors.forename: I
authors.initials: I
authors.lastname: Holme
authors.forename: J O
authors.initials: JO
authors.lastname: Syvertsen
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D017292:Doxazosin; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015849:Plasminogen Inactivators / Q000097:blood*; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D008055:Lipids; D015849:Plasminogen Inactivators; D005340:Fibrinogen; D017292:Doxazosin; D011224:Prazosin