Hypertension

Effectiveness of 2 Antihypertensives Further Explored

Sprionolactone and amiloride are safe and effective antihypertensive drugs for the treatment of salt-resistant hypertension, according to new findings.

In 3 substudies, the researchers evaluated 269 patients with resistant hypertension who were enrolled in the PATHWAY-2 study (N = 314). During the PATHWAY-2 study, patients treated with each of placebo, 25-50 mg spironolactone, 5-10 mg bisoprolol, and 4-8 mg doxazosin for 12 weeks.
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The following factors were assessed:

  • Substudy 1 (n = 126): Plasma aldosterone, renin, and aldosterone-to-renin ratio (ARR) as predictors of home systolic blood pressure.
  • Substudy 2 (n = 226): The effects of each drug in terms of thoracic fluid index, cardiac index, stroke index, and systemic vascular resistance.
  • Substudy 3 (n = 146): The effect of once-daily 10-20 mg amiloride on clinic systolic blood pressure during an optional 6-12 week open-label runout phase.

Results of the study indicated that ARR and plasma renin both predicted home systolic blood pressure reduction by spironolactone.

A total of 42 patients were found to have low renin concentrations, and 31 had inappropriately high aldosterone concentrations.

Spironolactone was associated with 6.8% reduction from baseline in thoracic fluid content. However, no other treatments demonstrated this effect.

Once-daily amiloride was associated with a 2.4-mm Hg reduction in systolic blood pressure, compared with an 18.3-mm Hg reduction with once-daily 25 mg spironolactone.

Mean plasma potassium concentrations were found to increase from 4.02 mmol/L with placebo to 4.50 mmol/L with amiloride.

“Our results suggest that resistant hypertension is commonly a salt-retaining state, most likely due to inappropriate aldosterone secretion,” the researchers wrote.

“Mineralocorticoid receptor blockade by spironolactone overcomes the salt retention and resistance of hypertension to treatment,” they concluded. “Amiloride seems to be as effective an antihypertensive as spironolactone, offering a substitute treatment for resistant hypertension.

No serious adverse events were noted.

—Christina Vogt

Reference:

Williams B, MacDonald TM, Morant SV, et al; the British Hypertension Society programme of Prevention And Treatment of Hypertension With Algorithm based Therapy (PATHWAY) Study Group. Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies. Lancet Diabetes Endocrinol. 2018;6(6):464-475. https://doi.org/10.1016/S2213-8587(18)30071-8