Objective: To review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of spironolactone in the treatment of resistant hypertension.
Data sources: A literature search was conducted using MEDLINE (1966-July 2010), International Pharmaceutical Abstracts (1970-July 2010), and Cochrane database (2009) for the key words spironolactone or resistant hypertension. References cited in the articles were reviewed for additional information.
Study selection and data extraction: English-language literature reporting pharmacology data from animal studies and clinical trials evaluating the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of spironolactone were included.
Data synthesis: Spironolactone is a potassium-sparing diuretic with anti-aldosterone effects that are beneficial in the management of hypertension. Spironolactone has shown improvement in 5 prospective studies and 1 retrospective study evaluating its blood pressuring-lowering abilities in patients with resistant hypertension. Specifically, the average blood pressure lowering noted in these trials with the addition of spironolactone in patients with resistant hypertension was 22/10 mm Hg. Trials evaluating spironolactone's role in resistant hypertension treatment have identified hyperkalemia, gynecomastia, and renal insufficiency as the major adverse effects that warrant monitoring.
Conclusions: Spironolactone is an appropriate antihypertensive medication to add to treatment of patients with resistant hypertension (≥3 antihypertensive medications at optimal doses) not at their blood pressure goal. In patients considered to have resistant hypertension, secondary causes should be ruled out.