Insulin action and hypertension: effects of hyperaldosteronism and its treatment

A randomised double‐blind control crossover design will be employed. All antihypertensive agents will be withdrawn and placebo substituted for six weeks. During this period blood pressure will be monitored every two weeks. There will be two study periods of 12 weeks during which blood pressure will be measured after two weeks and then every four weeks, separated by a six‐week washout during which blood pressure will be measured every two weeks. It is no longer ethical to compare with placebo and so we will compare with doxazosin, which has been shown to be neutral in its effect on insulin action. Patients will be started on eplerenone 25 mg twice daily or doxazosin 1 mg twice daily for the first week, 2 mg twice daily thereafter. Insulin action will be assessed at the end of the placebo run in and after each of the two study periods. Twenty‐four hour ambulatory blood pressure monitoring will be performed in the last week of placebo run‐in and each treatment period. If, during the study (including during placebo run‐in or wash‐out), systolic blood pressure rises above 160 mmHg or diastolic blood pressure rises above 100 mmHg on any occasion, or above 160 and 95 mmHg on two occasions, additional therapy with doxazosin will be given, with the addition of up to 12 mg of doxazosin. Serum creatinine and potassium will be measured at baseline and every four weeks during the active treatment periods. Insulin action will be measured by performing a hyperinsulinaemic, euglycaemic clamp, measured at the end of weeks 6, 18 and 36. Blood pressure will be measured using a standard automated blood pressure machine, measured at the end of weeks 2, 4, 6, 8, 12, 16, 18, 20, 22, 24, 26, 30, 34 and 36.