Effect of doxazosin gastrointestinal therapeutic system as third-line antihypertensive therapy on blood pressure and lipids in the Anglo-Scandinavian Cardiac Outcomes Trial

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 - alpha-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.