Methyldopa reduces blood pressure in people with high blood pressure

Methyldopa is a medication that has been used to treat high blood pressure since the 1960s. While there is some belief methyldopa 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 methyldopa reduces blood pressure, the nature of methyldopa's adverse effect profile, and to determine the clinical impact of its use for hypertension.The search revealed 12 trials with a total of 595 patients that were randomized to either a methyldopa treatment arm (296 patients) or a placebo treatment arm (299 patients). The daily doses of methyldopa used in these studies ranged 500-2250 mg daily. The most commonly studied daily dose of methyldopa was 750 mg daily. Most studies followed patients for four to six weeks of therapy. None of the studies reported on the clinical impact of methyldopa (e.g. if methyldopa reduced the risk of having a stroke 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 methyldopa reduces systolic/diastolic blood pressure by approximately 13/8 mmHg compared to placebo.

Authors' conclusions: 

Methyldopa lowers blood pressure to varying degrees compared to placebo for patients with primary hypertension. Its effect on clinical outcomes, however, remains uncertain.

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Background: 

Hypertension is associated with an increased risk of stroke, myocardial infarction and congestive heart failure. Methyldopa is a centrally acting antihypertensive agent, which was commonly used in the 1970's and 80's for blood pressure control. Its use at present has largely been replaced by antihypertensive drug classes with less side effects, but it is still used in developing countries due to its low cost. A review of its relative effectiveness compared to placebo on surrogate and clinical outcomes is justified.

Objectives: 

To quantify the effect of methyldopa compared to placebo in randomized controlled trials (RCTs) on all cause mortality, cardiovascular mortality, serious adverse events, myocardial infarctions, strokes, withdrawals due to adverse effects and blood pressure in patients with primary hypertension.

Search strategy: 

We searched the following databases: Cochrane Central Register of Controlled Trials (1960-June 2009), MEDLINE (2005-June 2009), and EMBASE (2007-June 2009). Bibliographic citations from retrieved studies were also reviewed. No language restrictions were applied.

Selection criteria: 

We selected RCTs studying patients with primary hypertension. We excluded studies of patients with secondary hypertension or gestational hypertension.

Data collection and analysis: 

Two reviewers independently extracted data and assessed trial quality using the risk of bias tool. Data synthesis and analysis was performed using RevMan 5. Data for blood pressure were combined using the generic inverse variance method.

Main results: 

Twelve trials (N=595) met the inclusion criteria for this review. None of these studies evaluated the effects of methyldopa compared to placebo on mortality and morbidity outcomes. Data for withdrawals due to adverse effects were not reported in a way that permitted meaningful meta-analysis. Data from six of the twelve trials (N=231) were combined to evaluate the blood pressure lowering effects of methyldopa compared to placebo. This meta-analysis shows that methyldopa at doses ranging from 500-2250 mg daily lowers systolic and diastolic blood pressure by a mean of 13 (95%CI 6-20) / 8 (95% CI 4-13) mmHg. Overall, the risk of bias was considered moderate.

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