Effect of Spironolactone on Blood Pressure in Subjects With Resistant Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 49; no. 4; pp. 839 - 845
• Main Authors: Chapman, Neil, Dobson, Joanna, Wilson, Sarah, Dahlöf, Björn, Sever, Peter S., Wedel, Hans, Poulter, Neil R.
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.04.2007
• Subjects: Aged; Aldosterone Antagonists/adverse effects/therapeutic use; Antihypertensive Agents - therapeutic use; Blood Pressure - drug effects; Breast - drug effects; Drug Resistance; Female; Gynecomastia - chemically induced; Humans; Hyperkalemia - chemically induced; Hypertension - drug therapy; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Mineralocorticoid Receptor Antagonists - adverse effects; Mineralocorticoid Receptor Antagonists - therapeutic use; Pain - chemically induced; Retreatment; Spironolactone - adverse effects; Spironolactone - therapeutic use; Spironolactone/adverse effects/therapeutic use; Treatment Outcome
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/01.HYP.0000259805.18468.8c

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 range2.0 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 range0.6 to 2.6 years). The median dose of spironolactone was 25 mg (interquartile range25 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% CI20.8 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 ≈3 other drugs. Although nonrandomized and not placebo controlled, these data support the use of spironolactone in uncontrolled hypertension.