The blood pressure lowering effect of ENaC blockers is not known

Potassium-sparing diuretics, which block the epithelial sodium channel (also called ENaC blockers), are a class of drugs commonly prescribed to prevent loss of potassium but also might help to lower elevated blood pressure. This class includes drugs such as amiloride (Midamor, Amilzide) and triamterene (Dyrenium, Dyazide). We asked how much this class of drugs lowers blood pressure, when used alone or when used as the second drug to treat hypertension. The available scientific literature was searched to find all the trials that had assessed this question. No trials were found studying the blood pressure lowering ability of ENaC blockers when used alone. We found 6 trials studying the blood pressure lowering ability of amiloride and triamterene, when added as a second drug, in 496 participants. All 6 trials studied the ENaC blockers at low doses and there was no blood pressure lowering effect. Trials studying these drugs at higher doses are needed in order to determine if they lower blood pressure. The harms associated with ENaC blockers could not be estimated in this review because of the low doses studied and the short duration of the trials.

Authors' conclusions: 

ENaC blockers do not have a statistically or clinically significant BP lowering effect at low doses but trials at higher doses are not available. The review did not provide a good estimate of the incidence of harms associated with ENaC blockers.

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Background: 

Potassium-sparing diuretics, which block the epithelial sodium channel (ENaC), are widely prescribed for hypertension as a second-line drug in patients taking other diuretics (e.g. thiazide diuretics) and much less commonly prescribed as monotherapy. Therefore, it is essential to determine the effects of ENaC blockers on blood pressure (BP), heart rate and withdrawals due to adverse effects (WDAEs) when given as a first-line or second-line therapy.

Objectives: 

To quantify the dose-related reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) of ENaC blocker therapy as a first-line or second-line drug in patients with primary hypertension.

Search strategy: 

We searched CENTRAL (The Cochrane Library 2012), MEDLINE (1950 to August 2012), EMBASE (1980 to August 2012) and reference lists of articles.

Selection criteria: 

Double-blind, randomized, controlled trials in patients with primary hypertension that evaluate, for a duration of 3 to 12 weeks, the BP lowering efficacy of: 1) fixed-dose monotherapy with an ENaC blocker compared with placebo; or 2) an ENaC blocker in combination with another class of anti-hypertensive drugs compared with the respective monotherapy (without an ENaC blocker).

Data collection and analysis: 

Two authors independently assessed the risk of bias and extracted data. Study authors were contacted for additional information. WDAE information was also collected from the trials.

Main results: 

No trials evaluating the BP lowering efficacy of ENaC blockers as monotherapy in patients with primary hypertension were identified. Only 6 trials evaluated the BP lowering efficacy of low doses of amiloride and triamterene as a second drug in 496 participants with a baseline BP of 151/102 mm Hg. The additional BP reduction caused by the ENaC blocker as a second drug was estimated by comparing the difference in BP reduction between the combination and monotherapy groups. The addition of low doses of amiloride and triamterene in these trials did not reduce BP. An estimate of the dose-related BP lowering efficacy for ENaC blockers was not possible because of a lack of trial data at higher doses.

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