What can I add to a blood pressure (BP) regimen consisting of amlodipine, losartan, and hydrochlorothiazide (HCTZ)?

Adding to a Blood Pressure Regimen with Amlodipine, Losartan, and HCTZ

A mineralocorticoid receptor antagonist like spironolactone (25-50 mg daily) is the most effective addition to your current triple therapy regimen of amlodipine, losartan, and hydrochlorothiazide for resistant hypertension. 1, 2

Rationale for Adding Spironolactone

Spironolactone has demonstrated remarkable efficacy in resistant hypertension:

• Studies show spironolactone can lower blood pressure by an additional 25/12 mmHg when added to existing multidrug regimens that include a diuretic and an ACE inhibitor/ARB 1
• This significant blood pressure reduction occurs regardless of baseline plasma aldosterone, renin activity, or aldosterone/renin ratio 1
• The American Heart Association specifically recommends mineralocorticoid receptor antagonists for patients whose blood pressure remains uncontrolled on a regimen like yours 2

Dosing and Monitoring

• Start with spironolactone 25 mg daily
• Can be titrated up to 50 mg daily if needed
• Monitor serum potassium and renal function within 3 months of starting treatment 2
• Continue monitoring every 6 months if levels remain stable 2

Important Considerations

• Risk of hyperkalemia: More common in older patients, those with diabetes or chronic kidney disease, or when combined with ACE inhibitors/ARBs. Close monitoring is essential 1
• Common side effect: Breast tenderness with or without enlargement, particularly in men 1
• Contraindications: Severe renal impairment, hyperkalemia

Alternative Option

If spironolactone is not tolerated or contraindicated, amiloride is an effective alternative:

• Functions as an indirect aldosterone antagonist by blocking epithelial sodium channels in the kidney 1
• Has demonstrated significant blood pressure reduction (31/15 mmHg) when combined with HCTZ in patients with resistant hypertension 1
• May be particularly effective in African American patients 1

Optimizing Current Regimen

Before adding a fourth agent, ensure:

1. Medication adherence is optimal
2. Sodium restriction (≤2.3 g/day) is being followed 2
3. Other lifestyle modifications are implemented:
   • DASH diet high in fruits, vegetables, low-fat dairy
   • Alcohol moderation (≤2 drinks/day for men, ≤1 drink/day for women)
   • Regular physical activity
   • Weight management 2

Timing Considerations

Consider administering at least one of your antihypertensive medications at bedtime, as this approach has been associated with better 24-hour blood pressure control and lower nighttime blood pressure values 1.