Spironolactone for hypertension.

BACKGROUND: Spironolactone is an aldosterone antagonist, considered fourth line therapy for hypertension in patients already treated with multiple medications.
OBJECTIVES: Primary: to determine the effect of spironolactone on patient mortality, morbidity, and to quantify the magnitude of blood pressure lowering effect of spironolactone monotherapy.Secondary: to determine the prevalence of adverse reactions observed with spironolactone monotherapy and to determine if there is a blood-pressure lowering dose response with spironolactone. SEARCH STRATEGY: We searched the following databases: Cochrane Central Register of Controlled Trials (3rd Quarter 2009), MEDLINE (2005 - Sept. 2009), and EMBASE (2007 - Sept. 2009). References from retrieved studies were reviewed to identify any studies missed in the initial search. No language restrictions were applied. SELECTION CRITERIA: We selected RCTs studying patients with primary hypertension. We excluded studies of patients with secondary or gestational hypertension, and studies where patients were receiving multiple antihypertensives. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed the search results for studies meeting our criteria. Three reviewers extracted data and assessed trial quality using a standardized data extraction form. Data synthesis and analysis was performed using RevMan 5. MAIN
RESULTS: Meta-analysis of the 5 cross-over studies found a reduction in SBP of 20.09 mmHg (95%CI:16.58-23.06,p<0.00001) and a 6.75 mmHg (95%CI:4.8-8.69,p<0.00001) reduction in DBP. These results were statistically significant and there was no evidence of heterogeneity between the studies. There may be a dose response effect with spironolactone up to 50 mg/day, but the confidence intervals around the mean end-of-study blood pressure for doses ranging 25-500 mg/day all overlapped. In other words, it appears that doses >50mg/day do not produce further reductions in either SBP or DBP. One cross-over study found that spironolactone 25 mg/day did not statistically significantly change SBP or DBP compared to placebo, SBP: -9.9 (95%CI:-21.15,1.35); DBP -2.34 (95%CI:-7.92,3.06). AUTHORS'
CONCLUSIONS: From the limited available evidence, spironolactone appears to lower blood pressure compared to placebo to a similar degree in patients with primary (essential) hypertension when doses of 100-500 mg/day are given. A dose of 25 mg/day did not statistically significantly reduce systolic or diastolic blood pressure, compared to placebo. Given the lack of a dose-response, coupled with a possible increased risk in adverse events with higher doses, doses of 25 to 100 mg/day are reasonable. There is no evidence of the effect of spironolactone on clinical outcomes in hypertensive patients.