What to do next for a patient with elevated blood pressure (hypertension) despite being on amlodipine (calcium channel blocker) 5 mg daily and valsartan (angiotensin II receptor blocker)/HCTZ (hydrochlorothiazide, diuretic) 320/25 mg daily, with lower extremity edema?

Management of Hypertension with Lower Extremity Edema on Amlodipine

The most appropriate next step is to switch from amlodipine to a different antihypertensive medication while optimizing the valsartan/HCTZ dosing, as amlodipine is causing lower extremity edema and blood pressure remains uncontrolled at 138/90 mmHg.

Current Medication Assessment

The patient is currently on:

• Amlodipine 5 mg daily (causing lower extremity edema)
• Valsartan/HCTZ 320/25 mg daily
• Blood pressure remains elevated at 138/90 mmHg

Recommended Management Strategy

Step 1: Address the Amlodipine-Induced Edema

• Peripheral edema is a common side effect of amlodipine and other dihydropyridine calcium channel blockers (CCBs)
• Studies show that combining amlodipine with ARBs like valsartan can reduce the incidence of edema compared to amlodipine monotherapy, but the patient is already on this combination and still experiencing edema 1
• Consider discontinuing amlodipine and replacing it with a different class of antihypertensive medication

Step 2: Optimize Therapy Based on Guidelines

1. Replace amlodipine with a different antihypertensive agent:

   • Consider adding a mineralocorticoid receptor antagonist (MRA) such as spironolactone or eplerenone
   • The American Heart Association recommends MRAs for patients with resistant hypertension 2
   • Aldosterone receptor antagonists have shown a 30% reduction in mortality in heart failure patients and may be particularly beneficial in patients with hypertension 2

2. Ensure optimal dosing of current medications:

   • The patient is already on maximum doses of valsartan (320 mg) and HCTZ (25 mg)
   • Consider switching from HCTZ to chlorthalidone, which provides greater 24-hour blood pressure reduction 3

Evidence-Based Rationale

1. Amlodipine and edema:

   • Peripheral edema occurs in up to 31.1% of patients on amlodipine 10 mg 1
   • In rare cases, amlodipine can cause generalized edema (anasarca) 4
   • Discontinuation of amlodipine typically results in resolution of edema 4

2. Alternative medication options:

   • Spironolactone or eplerenone (MRAs) are effective options for resistant hypertension
   • The RALES trial showed a 30% reduction in mortality with spironolactone in heart failure patients 2
   • The EPHESUS trial demonstrated a 15% improvement in mortality with eplerenone 2
   • The improvement in relative risk with eplerenone was greater in patients with a history of hypertension 2

3. Target blood pressure:

   • For most adults, target blood pressure should be <130/80 mmHg 2, 3
   • In patients with heart failure, consideration should be given to lowering BP even further, to <120/80 mmHg 2

Potential Pitfalls and Cautions

1. Medications to avoid:

   • Non-dihydropyridine CCBs (diltiazem, verapamil) should be avoided, especially if the patient has heart failure, due to negative inotropic properties 2
   • Alpha-blockers like doxazosin should be avoided due to increased risk of heart failure 2, 3
   • Clonidine should be avoided in heart failure patients due to potential increased mortality risk 2

2. Monitoring recommendations:

   • Monitor renal function and electrolytes within 3 months of starting new therapy, particularly if adding an MRA 3
   • Ensure diastolic BP does not fall below 60 mmHg, especially in patients over 60 years or with diabetes 3
   • Consider home blood pressure monitoring to guide treatment adjustments 3

By discontinuing amlodipine and adding an MRA like spironolactone, you can address both the lower extremity edema and improve blood pressure control while potentially providing additional cardiovascular benefits.