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(Circulation. 2008;118:42-48.)
© 2008 American Heart Association, Inc.

Hypertension

Effect of Doxazosin Gastrointestinal Therapeutic System as Third-Line Antihypertensive Therapy on Blood Pressure and Lipids in the Anglo-Scandinavian Cardiac Outcomes Trial

Neil Chapman, FRCP; Choon Lan Chang, PhD; Björn Dahlöf, MD, PhD; Peter S. Sever, FRCP; Hans Wedel, PhD; Neil R. Poulter, FRCP, on behalf of the ASCOT Investigators

From the Imperial College (N.C., C.L.C., P.S.S., N.R.P.), London, United Kingdom; Sahlgrenska University Hospital (B.D.), Göteborg, Sweden; and Nordic School of Public Health (H.W.), Göteborg, Sweden.

Correspondence to Dr N. Chapman, International Centre for Circulatory Health, Imperial College London, 59 N Wharf Rd, London W2 1PG, United Kingdom. E-mail neil.chapman{at}imperial.nhs.uk

Received September 3, 2007; accepted April 18, 2008.

Background— The role of doxazosin in treatment of hypertension remains controversial.

Methods and Results— We evaluated the effects on blood pressure (BP) and biochemical parameters of doxazosin GITS (gastrointestinal therapeutic system) as a third-line antihypertensive agent among 10 069 participants in the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm (ASCOT-BPLA) whose BP remained above 140/90 mm Hg (130/80 mm Hg in those with diabetes mellitus). Among those who received doxazosin, mean age was 63 years (SD 9 years), 79% were male, and 32% had diabetes. Doxazosin was initiated a median of 8 months (interquartile range 3 to 24 months) after randomization and was added to a mean of 2.0 (SD 0.3) other antihypertensive drugs; the mean starting and final doses were 4.1 (SD 0.6) and 7.0 (SD 3.1) mg, respectively. During a median of 12 months (interquartile range 4 to 31 months) of uninterrupted doxazosin treatment, during which other antihypertensive treatments remained unchanged, mean BP fell 11.7/6.9 mm Hg (SD 18.8/9.6 mm Hg, P<0.0001) from 158.7/89.2 mm Hg (SD 18.3/10.6 mm Hg). After the addition of doxazosin, 29.7% of participants achieved target BP. There was no apparent excess of heart failure among doxazosin users. There were associated modest favorable effects on plasma lipid profiles, but a small rise in fasting plasma glucose was observed. Doxazosin was generally well tolerated, with 7.5% of participants discontinuing the drug because of adverse events, most frequently dizziness, fatigue, headache, and edema.

Conclusions— -Blockers are no longer recommended as add-on therapy in some hypertension guidelines. However, although they are nonrandomized and were not placebo-controlled, the present findings suggest that doxazosin is a safe and effective third-line antihypertensive agent.

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Circulation 2008 118: 1-2. [Extract] [Full Text]