Spironolactone for the treatment of high blood pressure

Spironolactone is a medication that has been used to treat high blood pressure since the 1960s. While there is some belief spironolactone reduces blood pressure, there are concerns due to the potential for this drug to cause adverse effects. The aim of this review was to determine the extent to which spironolactone reduces blood pressure, the nature of spironolactone’s adverse effect profile, and to determine the clinical impact of its use for hypertension. The search revealed 5 cross-over trials with a total of 137 patients that received both spironolactone followed by placebo or vice verse, in a random order. One other trial was found that randomly gave 42 patients either spironolactone (22 patients) or placebo (20 patients). The daily doses of spironolactone used in these studies ranged from 25-500 mg daily. Studies followed patients for 4 to 8 weeks of therapy. None of the studies reported on the clinical impact of spironolactone (i.e. whether spironolactone reduced heart attacks or strokes compared to placebo). Overall reporting of adverse effects was poor so no conclusions can be drawn about the adverse effect profile. This meta-analysis shows that spironolactone reduces systolic/diastolic blood pressure by approximately 20/7 mm Hg compared to placebo.

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.

Read the full abstract...
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).

Share/Save