Management of resistant arterial hypertension: role of spironolactone versus double blockade of the renin-angiotensin-aldosterone system.

Background: Currently there is no consensus regarding which add-on therapy to use in resistant hypertension. This study was designed to compare two treatment options, spironolactone (SPR) versus dual blockade of the renin-angiotensin-aldosterone system (RAAS).

Methods: Forty-two patients with true resistant hypertension were included in the study. An open-label prospective crossover design was used to add a second RAAS blocker to previous treatment and then SPR following 1 month of wash-out. BP was measured in the office and by ambulatory blood pressure monitoring (ABPM). Changes in laboratory tests were also studied for both treatments. The predictive values of aldosterone-renin ratio (ARR) and serum potassium of determining the antihypertensive response were analyzed for both arms.

Results: Following the first stage of dual blockade, SBP dropped significantly both in office (reduction of 12.9 ± 19.2 mmHg)) and by ABPM (reduction of 7.1 ± 13.4 mmHg). Office DBP was unchanged but was significantly reduced as measured by ABPM (3.4 ± 6.2 mmHg). On SPR treatment, office BP was reduced 32.2 ± 20.6/10.9 ± 11.6 mmHg. By ABPM the reduction was 20.8 ± 14.6/8.8 ± 7.3 mmHg (P < 0.001). The BP control was achieved by 25.6% of patients in dual blockade and 53.8% in SPR with office blood pressure. By ABPM, 20.5% were controlled on dual blockade and up to 56.4% with SPR. Serum potassium was a weak inverse predictor of the blood pressure-lowering effect of SPR.

Conclusion: SPR has a greater antihypertensive effect than dual blockade of the RAAS in resistant hypertension. SPR at daily doses of 25-50 mg shows a potent antihypertensive effect when added to prior regimes of single RAAS axis blockade in patients with resistant arterial hypertension.