[150,151] Compared to placebo, spironolactone reduced office SBP/DBP by an average of 15.73/6.21 mm Hg and 24-hour ambulatory or home SBP/DBP by 8.70/4.12 mm Hg.[150] More limited studies of another MRA, eplerenone,[152] and an epithelial sodium channel blocker, amiloride,[153] suggest that they have qualitatively similar effects on blood pressure as spironolactone in patients with RHT. Compared with clonidine or spironolactone, the addition of other antihypertensive drugs (notably candesartan, doxazosin, bisoprolol, ramipril, atenolol, or alpha methyldopa) to the three-drug regimen of patients with RHT were less effective in reducing blood pressure.[150,154] It should be noted, however, that there are no studies which directly compare either amiloride or eplerenone with spironolactone in patients with RHT. From a safety perspective, spironolactone, eplerenone, and amiloride all consistently resulted in a modest increase in serum potassium. The longest period of evaluation of the effect of spironolactone, another antihypertensive drug, or placebo on blood pressure in these RCTs was 24 weeks. Thus, it was not possible to determine the effect of the drugs on cardiovascular outcomes. However, one RCT, the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT), included patients who met the criteria for RHT.[155] A subset of 403 of the study participants from the Americas (U.S., Canada, Argentina, and Brazil) had RHT; 1,361 patients without RHT served as the comparator group. Patients were treated for an average of 2.92 years with either spironolactone or placebo in addition to their three-drug therapy. SBP in the spironolactone group was lower than in the placebo group at four weeks and remained significantly lower for at least eight months. The significantly greater reduction in the primary endpoint in spironolactone- versus placebo-treated patients was comparable in those with and without RHT. 