The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio

There is continuing variation in diagnosis and estimated prevalence of primary hyperaldosteronism. The higher estimates encourage search for adrenal adenomas in patients with elevated ratios of plasma aldosterone to renin. However, it is more likely that patients with normal plasma K+ and aldosterone belong to the polygenic spectrum of low-renin hypertension rather than have the same monogenic syndrome as classic Conn's. Our primary hypothesis was that in low-renin patients with normal plasma K+ and aldosterone, a thiazide diuretic, bendroflumethiazide, would be as effective as spironolactone in overcoming the Na+ retention and lowering blood pressure. Secondary objectives were to compare the dose response for each diuretic and to evaluate amiloride as an alternative to spironolactone. Fifty-seven patients entered and 51 patients completed a placebo-controlled, double-blind, randomized crossover trial. Entry criteria included low plasma renin, normal K+, elevated aldosterone-renin ratio, and a previous systolic blood pressure response to spironolactone of > or = 20 mm Hg. Two doses each of spironolactone and bendroflumethiazide were compared. The crossover also included amiloride and losartan. Outcome measures were blood pressure, plasma renin, and other biochemical markers of diuretic action. Spironolactone 100 mg and bendroflumethiazide 5 mg caused similar falls in systolic blood pressure, whereas bendroflumethiazide 2.5 mg was 5/2 mm Hg less effective in reducing blood pressure than either bendroflumethiazide 5 mg or spironolactone 50 mg (P