Alpha‐1 Adrenoceptor Blockade with Doxazosin in Hypertension: Effects on Blood Pressure and Lipoproteins

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Abstract
The effects of doxazosin, a long‐acting alpha‐1 adrenoreceptor blocking drug, were observed upon blood pressure and serum lipoproteins. Thirty patients with supine diastolic blood pressure between 90 and 114 mm Hg during single‐blind placebo therapy were randomized to double‐blind treatment with either doxazosin or further placebo in a parallel‐design protocol. Starting at one mg, dosage was doubled every 2 weeks during a 10‐week treatment period to a maximum dose of 16 mg once daily. Blood was sampled in the fasting state before and during double‐blind therapy for measurement of total cholesterol and triglycerides, cholesterol in the lipoprotein fractions, and apolipoproteins A and B. At the end of 10 weeks of titration, systolic and diastolic blood pressure were each reduced by 14 mm Hg in the standing position when measured 24 hours following the previous dose. Supine pressure was lowered by 6 mm Hg systolic and by 5 mm Hg diastolic at the same time point. Measured hourly for 12 hours following the ingestion of doxazosin, blood pressure was lowered maximally at 4–5 hours when an additional decline of 14/6 mm Hg (systolic/diastolic) was observed in the standing position and 13/6 in the supine posture. Postural dizziness, the most frequent symptomatic complaint, was reported in 4 patients during doxazosin treatment. After brief interruption of treatment in one and dosage adjustment in another, titration was continued in all four and no patient was withdrawn because of side effects. Concerning lipoproteins, the ratio of total cholesterol to HDL cholesterol and of LDL to HDL cholesterol both improved during treatment with doxazosin. Although these changes did not differ from those in the placebo group, the findings indicate that both blood pressure and lipoprotein concentrations respond favorably during treatment with doxazosin. This favorable combination of effects on CHD risk factors is matched by few other classes of antihypertensive drugs. In this way doxazosin offers a distinct advantage as first‐line therapy of hypertension.