The Efficacy of Spironolactone in Patients With Resistant Hypertension
The Efficacy of Spironolactone in Patients With Resistant Hypertension
To determine the efficacy of the addition of spironolactone to modern blood pressure lowering
 treatment regimens in patients with resistant hypertension (whose blood pressure is
 uncontrolled despite three blood pressure lowering drugs)
Objective: To assess the antihypertensive efficacy of adding spironolactone to the
 antihypertensive treatment of patients with resistant hypertension.

 Background and Rationale: The proportion of hypertensive patients meeting the definition of
 resistant hypertension is growing rapidly as doctors use more combination antihypertensive
 treatments in order to reach lower target blood pressures. Spironolactone is often used in
 specialist clinics for patients with resistant hypertension although it is currently only
 licensed in the UK for use in hypertension complicated by primary hyperaldosteronism.
 Uncontrolled studies suggest that spironolactone is a very effective antihypertensive in the
 modern management of resistant hypertension but we could find no randomised trials in this
 setting. In the Sheffield Hypertension Clinic spironolactone is currently used as one of the
 drugs of choice in patients with resistant hypertension, particularly in women and is
 anecdotally often very effective.

 Study methods. The study will be a double- blind randomised placebo controlled trial with a
 parallel group design assessing the addition of 25mg spironolactone to existing
 antihypertensive treatment, titrated to 50mg if necessary in 40 patients with resistant
 hypertension (20 patients per group) over a period of 6 weeks. Resistant hypertension will be
 defined as: blood pressures not adequately controlled (systolic blood pressure (SBP) >140
 mmHg and/or diastolic blood pressure (DBP) >85 mmHg in clinic and on ambulatory blood
 pressure monitoring) despite treatment with the maximum tolerated dose of three
 antihypertensive agents. All patients' current antihypertensive treatment will include a
 thiazide diuretic and at least one of a beta-blocker, angiotensin converting enzyme inhibitor
 or angiotensin II receptor antagonist. The primary endpoint will be the difference between
 the spironolactone and placebo groups in change in daytime average systolic blood pressure on
 24-hour ambulatory blood pressure monitoring from day 0 to day 42.
Inclusion Criteria:

 -  Aged over 18 years

 -  Hypertension (essential or secondary) managed in Sheffield Hypertension Clinic or
 general practice or both.

 -  Blood pressures not adequately controlled (systolic blood pressure (SBP) >140 mmHg
 and/or diastolic blood pressure (DBP) >85 mmHg in clinic and on ambulatory blood
 pressure monitoring) despite treatment with the maximum tolerated dose of three
 antihypertensive agents.

 -  Additional antihypertensive treatment deemed appropriate by the patients' doctor.

 -  Patients' current antihypertensive treatment includes a thiazide diuretic and at least
 one of a beta-blocker, angiotensin converting enzyme inhibitor or angiotensin II
 receptor antagonist.

 Exclusion Criteria:

 -  Definite indication or contraindication for spironolactone

 -  Known Conn's syndrome (definite indication for spironolactone)

 -  Heart failure NYHA class III or IV (definite indication for spironolactone)

 -  Known hepatic failure or significant cirrhosis

 -  Known pregnancy or women planning pregnancy

 -  Women of child bearing potential not using adequate contraceptive methods

 -  Serum creatinine > 221µmol/l

 -  Serum Potassium > 5.0mmol/l

 -  Clinic blood pressure or daytime ambulatory blood pressure >240/120