Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT-EXT): a randomized, double-blind, placebo-controlled trial

Purpose: There is currently limited data on which drug should be used to improve blood pressure control in patients with resistant hypertension. This study was designed to assess the effect of the addition of 25 mg of spironolactone on blood pressure (BP) in patients with resistant arterial hypertension. Methods: Patients with office systolic BP >140 mm Hg or diastolic BP >90 mm Hg despite treatment with at least 3 antihypertensive drugs including a diuretic, were enrolled in this double-blind, placebo-controlled, multicentre trial. 161 patients were randomly assigned to receive spironolactone or a placebo in a 1:1 ratio by the method of simple randomisation. Our primary endpoint was to show a statistically significant difference in the fall of mean day-time systolic and diastolic pressure by ambulatory blood pressure monitoring (ABPM), between the spironolactone and placebo groups, after 8 weeks of treatment. This study was registered with ClinicalTrials.gov, number NCT00524615. Results: Analyses were done with 150 patients (74 in the spironolactone and 76 in the placebo group). At 8 weeks, the difference in mean fall of BP on day-time ambulatory blood pressure monitoring (ABPM) between the groups was -9.8 mm Hg for systolic (p<0.001) and -3.3 mm Hg for diastolic BP (p=0.013). The APBM night-time systolic, 24-hour ABPM systolic and office systolic BP values were significantly decreased by spironolactone (difference of -13.0, -10.5 and -9.9 mm Hg; p<0.001 for all), as were the respective diastolic BP values (-6.4, -3.5 and -3.0 mm Hg; p<0.001, p=0.005 and p=0.003). Conclusions: Spironolactone treatment in patients with resistant arterial hypertension leads to a significant decrease of both systolic and diastolic blood pressure.