Add an ACE Inhibitor or ARB as the Second Agent
For a patient on amlodipine 10mg daily with blood pressure still in the 170s/80s, add either an ACE inhibitor (such as lisinopril 10-20mg daily) or an ARB (such as losartan 50-100mg daily) to achieve guideline-recommended dual therapy. 1
Rationale for ACE Inhibitor/ARB Addition
The combination of amlodipine with an ACE inhibitor or ARB provides complementary mechanisms of action—the calcium channel blocker causes vasodilation while the renin-angiotensin system blocker reduces volume and vascular resistance. 1
This combination has demonstrated superior blood pressure control compared to either agent alone, particularly in patients with diabetes, chronic kidney disease, or heart failure. 1
Adding an ACE inhibitor or ARB may actually reduce the peripheral edema that commonly occurs with amlodipine monotherapy, providing a dual benefit. 1
Alternative Option: Thiazide Diuretic
Adding a thiazide-like diuretic (chlorthalidone 12.5-25mg daily or hydrochlorothiazide 25-50mg daily) to amlodipine is equally effective, particularly for elderly patients or those with volume-dependent hypertension. 1
For Black patients specifically, the combination of amlodipine plus a thiazide diuretic may be more effective than amlodipine plus an ACE inhibitor/ARB. 1
Chlorthalidone is preferred over hydrochlorothiazide due to its longer duration of action. 1
Monitoring After Adding Second Agent
Target blood pressure should be <140/90 mmHg minimum, ideally <130/80 mmHg for higher-risk patients. 1
Reassess blood pressure within 2-4 weeks after adding the second agent, with the goal of achieving target blood pressure within 3 months of treatment modification. 1
Monitor for specific side effects: cough, hyperkalemia, and acute kidney injury with ACE inhibitors; hyperkalemia and acute kidney injury with ARBs; hypokalemia, hyperuricemia, and glucose intolerance with thiazide diuretics. 1
Check serum potassium and creatinine 2-4 weeks after initiating an ACE inhibitor, ARB, or diuretic therapy. 1
If Blood Pressure Remains Uncontrolled
If blood pressure remains uncontrolled after adding a second agent at optimal dose, add a third agent from the remaining class (creating triple therapy with ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic). 1
Never combine an ACE inhibitor with an ARB—this increases adverse effects without additional benefit. 1
Common Pitfalls to Avoid
Do not add a third drug class before maximizing doses of the current two-drug regimen, as this violates guideline-recommended stepwise approaches and exposes patients to unnecessary polypharmacy. 1
Confirm medication adherence before assuming treatment failure, as non-adherence is the most common cause of apparent treatment resistance. 1
Verify elevated readings with home blood pressure monitoring (target <135/85 mmHg) or 24-hour ambulatory monitoring (target <130/80 mmHg) to confirm true uncontrolled hypertension. 1