Therefore, this recommendation is based on evidence cited in the 2014 VA/DoD HTN CPG.[137,144,149] The Work Group determined there is some variation in patient values and preferences as some patients may prefer reducing the number of pills but fixed-dose combination therapy may not always be available (e.g., in the desired drug combination or strength) or prescribed. b. For Resistant Hypertension Recommendation 28. For patients with resistant hypertension (defined as those who are not adequately controlled with maximally tolerated dose of triple therapy [i.e., a thiazide-type diuretic, calcium channel blockers, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker]), we suggest adding spironolactone in those patients without contraindications. (Weak for | Reviewed, New-replaced) Discussion The mineralocorticoid receptor antagonist (MRA) spironolactone more effectively reduced SBP and DBP compared to placebo when added as the fourth agent to the treatment regimen of patients with resistant HTN (RHT).[150,151] In patients with a history of hyperkalemia and diminished renal function, spironolactone should be used cautiously and with frequent monitoring of potassium and renal function in RHT patients, and should be avoided altogether in patients with eGFR less than 30 ml/min/1.73M2 or a serum potassium greater than 5.0 mEq/L. Since spironolactone has both antiandrogenic and endocrine effects, it should also be used cautiously in patients with menstrual irregularities, breast pain or gynecomastia. Two SRs that included five RCTs of 662 patients with RHT and four RCTs of 553 patients with RHT, respectively, compared spironolactone to placebo or to ramipril.[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.