Resistant Hypertension Management

Definition and Diagnosis

Resistant hypertension is defined as blood pressure that remains above goal (>140/90 mmHg) despite concurrent use of three antihypertensive agents of different classes, including a diuretic, at optimal doses, affecting approximately 10-15% of hypertensive patients and is associated with increased cardiovascular risk 1

The American College of Cardiology recommends spironolactone (25-50 mg daily) as the most effective add-on therapy for resistant hypertension, providing significant blood pressure reduction when added to existing multidrug regimens, with a systolic and diastolic pressure reduction of 25 mmHg and 12 mmHg respectively 1
Spironolactone is effective across different patient populations, including both African American and white patients, with blood pressure response not predicted by baseline plasma aldosterone, urinary aldosterone, plasma renin activity, or aldosterone/renin ratio 1
The dose range for spironolactone is 25-100 mg daily, with common adverse effects including gynecomastia and breast tenderness, more common with spironolactone than eplerenone 2, 3
Spironolactone reduces choroidal thickness and subretinal fluid in patients with Central Serous Chorioretinopathy (CSC), with 56% of patients achieving complete resolution of subretinal fluid in a randomized controlled trial 4

Eplerenone (50-100 mg daily) is a more selective mineralocorticoid receptor antagonist with fewer anti-androgenic effects, though it may require twice-daily dosing for adequate BP lowering, and can be used as an alternative if spironolactone is not tolerated 2, 3
Amiloride (10-40 mg/day) can be substituted for patients with tender gynecomastia 5

Electrolyte monitoring is necessary, with checks for serum potassium and creatinine before initiation and periodically during treatment, and use should be avoided with potassium supplements, and cautiously in patients with significant renal dysfunction 2, 3
The American College of Cardiology recommends monitoring serum potassium and creatinine, especially in patients with chronic kidney disease, diabetes mellitus, or concomitant use of ACE inhibitors/ARBs, due to the risk of hyperkalemia 5
Spironolactone can cause anti-androgenic effects, including gynecomastia and breast tenderness, menstrual irregularities, and decreased libido 4, 5

The American College of Cardiology recommends confirming true resistant hypertension, optimizing existing regimen, adding spironolactone as fourth agent, and monitoring for efficacy and adverse effects, with a starting dose of 25 mg daily and reassessment of BP after 6 weeks 1, 2, 3
The American Heart Association recommends adding spironolactone after optimizing a 3-drug regimen for resistant hypertension, providing significant blood pressure reduction when added to multidrug regimens 6
The PATHWAY-2 trial demonstrated superiority of spironolactone over alpha and beta blockers in resistant hypertension 2
A daily dose of 25-50 mg of spironolactone is typically effective for resistant hypertension and Central Serous Chorioretinopathy 7, 4, 8