Spironolactone for hypertension.

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).

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.

• Authors: Josh Batterink, Sarah N Stabler, Aaron M Tejani, Curt T Fowkes
• Journal: The Cochrane database of systematic reviews (Cochrane Database Syst Rev) Issue 8 Pg. CD008169 (Aug 04 2010) ISSN: 1469-493X [Electronic] England
• PMID: 20687095 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)

Chemical References

• Antihypertensive Agents
• Spironolactone

Topics

• Antihypertensive Agents (adverse effects, therapeutic use)
• Blood Pressure (drug effects)
• Cross-Over Studies
• Humans
• Hypertension (drug therapy)
• Randomized Controlled Trials as Topic
• Spironolactone (adverse effects, therapeutic use)