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on February 19, 2007

Hypertension. 2007
Published online before print February 19, 2007, doi: 10.1161/01.HYP.0000259805.18468.8c
A more recent version of this article appeared on April 1, 2007
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Submitted on September 8, 2006
Revised on September 29, 2006

Effect of Spironolactone on Blood Pressure in Subjects With Resistant Hypertension

Neil Chapman*; Joanna Dobson; Sarah Wilson; Björn Dahlöf; Peter S. Sever; Hans Wedel; Neil R. Poulter; on behalf of the Anglo-Scandinavian Cardiac Outcomes Trial Investigators

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

* To whom correspondence should be addressed. E-mail: neil.chapman{at}st-marys.nhs.uk.

Abstract--Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication. We evaluated the effect among 1411 participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm who received spironolactone mainly as a fourth-line antihypertensive agent for uncontrolled blood pressure and who had valid BP measurements before and during spironolactone treatment. Among those who received spironolactone, the mean age was 63 years (SD: ±8 years), 77% were men, and 40% had diabetes. Spironolactone was initiated a median of 3.2 years (interquartile range: 2.0 to 4.4 years) after randomization and added to a mean of 2.9 (SD: ±0.9) other antihypertensive drugs. The median duration of spironolactone treatment was 1.3 years (interquartile range: 0.6 to 2.6 years). The median dose of spironolactone was 25 mg (interquartile range: 25 to 50 mg) at both the start and end of the observation period. During spironolactone therapy, mean blood pressure fell from 156.9/85.3 mm Hg (SD: ±18.0/11.5 mm Hg) by 21.9/9.5 mm Hg (95% CI: 20.8 to 23.0/9.0 to 10.1 mm Hg; P<0.001); the BP reduction was largely unaffected by age, sex, smoking, and diabetic status. Spironolactone was generally well tolerated; 6% of participants discontinued the drug because of adverse effects. The most frequent adverse events were gynecomastia or breast discomfort and biochemical abnormalities (principally hyperkaliemia), which were recorded as adverse events in 6% and 2% of participants, respectively. In conclusion, spironolactone effectively lowers blood pressure in patients with hypertension uncontrolled by a mean of {approx}3 other drugs. Although nonrandomized and not placebo controlled, these data support the use of spironolactone in uncontrolled hypertension.


Key words: blood pressure • hypertension • clinical trial • antihypertensive agents • aldosterone antagonists • spironolactone


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