title: Effect of spironolactone on blood pressure in subjects with resistant hypertension.
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 approximately 3 other drugs. Although nonrandomized and not placebo controlled, these data support the use of spironolactone in uncontrolled hypertension.
authors.affiliation: International Centre for Circulatory Health, Imperial College London, 59 North Wharf Rd, London W2 1PG, United Kingdom. neil.chapman@st-marys.nhs.uk
authors.forename: Neil
authors.initials: N
authors.lastname: Chapman
authors.forename: Joanna
authors.initials: J
authors.lastname: Dobson
authors.forename: Sarah
authors.initials: S
authors.lastname: Wilson
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlöf
authors.forename: Peter S
authors.initials: PS
authors.lastname: Sever
authors.forename: Hans
authors.initials: H
authors.lastname: Wedel
authors.forename: Neil R
authors.initials: NR
authors.lastname: Poulter
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D001940:Breast / Q000187:drug effects; D004351:Drug Resistance; D005260:Female; D006177:Gynecomastia / Q000139:chemically induced; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D010146:Pain / Q000139:chemically induced; D019233:Retreatment; D013148:Spironolactone / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone