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Spironolactone for Drug-Resistant Hypertension

Is it superior to other add-on drugs?

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Spironolactone was the most effective add-on drug for the treatment of resistant hypertension in a double-blind, placebo-controlled study of 285 randomly assigned patients aged 18 to 79 years who received spironolactone, doxazosin, biosoprolol, and placebo in addition to their baseline blood pressure medications. Participants had seated clinic systolic blood pressure (BP) of ≥140 mm Hg and home systolic BP of ≥130 mm Hg, despite treatment for at least 3 months with maximally tolerated doses of 3 drugs. Researchers found:

• Average reduction in home systolic BP by spironolactone was superior to placebo (-8.70 mm Hg).

• Average reduction in home systolic BP by spironolactone was superior to the mean of other 2 active treatments (doxazosin and bisoprolol; 4.26 mm Hg) and when compared with the individual treatments vs doxazosin (-4.03 mm Hg) and vs. bisoprolol (-4.48 mm Hg).

• Superiority of spironolactone supports a primary role of sodium retention in patients with resistant hypertension.

Citation: Williams B, MacDonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomized, double-blind, crossover trial. Lancet. [Published online ahead of print September 21, 2015]. doi: 10.1016/S0140-6736(15)00257-3.

Commentary: Resistant hypertension (RH), defined as a BP that remains above goal despite concurrent use of 3 antihypertensive agents of different classes at maximal or near maximal doses, occurs in approximately 20% of patients with hypertension. First step in treating RH is making sure that 1 of the 3 agents used is a diuretic. Other guideline recommendations are that primary hyperaldosteronism is an underappreciated secondary cause of RH, occurring in 20% of patients with RH. A complete metabolic panel, urinalysis, and a paired, morning plasma aldosterone and plasma renin are indicated in evaluation of RH. After considering secondary causes, lifestyle interventions and potential BP decreases include weight loss (5 mm Hg), low-salt diet (8 mm Hg), exercise (5 mm Hg), and a high-fiber, low-fat (DASH) diet (10 mm Hg). Medications recommended for RH include chlorthalidone, spironolactone or amiloride, and perhaps combined alpha/beta antagonists1. —Neil Skolnik, MD

1. Calhoun DA. Resistant hypertension: Diagnosis, evaluation, and treatment: A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 2008;51;1403-1419.

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