What medication should be added to lisinopril (Angiotensin-Converting Enzyme Inhibitor) 20mg daily for a 49-year-old male with uncontrolled hypertension?

Add a Calcium Channel Blocker or Thiazide Diuretic to Lisinopril 20mg

For this 49-year-old male with uncontrolled hypertension on lisinopril 20mg daily, add either amlodipine 5-10mg daily or a thiazide diuretic (hydrochlorothiazide 12.5-25mg or chlorthalidone 12.5-25mg) as the second agent to achieve guideline-recommended dual therapy. 1

Rationale for Adding a Second Agent

• The current lisinopril dose of 20mg is within the usual therapeutic range (20-40mg daily), but adding a second agent from a different class is more effective than simply increasing the ACE inhibitor dose for uncontrolled hypertension 1, 2
• The American College of Cardiology guidelines recommend a stepwise approach: start with an ACE inhibitor, then add either a calcium channel blocker or thiazide diuretic if blood pressure remains above target 1

First Choice: Calcium Channel Blocker (Amlodipine)

• Adding amlodipine 5-10mg daily to lisinopril provides complementary mechanisms of action—vasodilation through calcium channel blockade combined with renin-angiotensin system inhibition—which demonstrates superior blood pressure control compared to either agent alone 1
• This combination is particularly beneficial for patients with chronic kidney disease, heart failure, or coronary artery disease 1
• Amlodipine may attenuate peripheral edema that can occur with calcium channel blocker monotherapy when combined with an ACE inhibitor 1

Alternative Choice: Thiazide Diuretic

• Adding hydrochlorothiazide 12.5-25mg daily or chlorthalidone 12.5-25mg daily is an effective alternative, particularly for patients with volume-dependent hypertension or elderly patients 1
• The FDA label specifically states: "If blood pressure is not controlled with lisinopril tablets alone, a low dose of a diuretic may be added (e.g., hydrochlorothiazide, 12.5 mg)" 2
• Chlorthalidone is preferred over hydrochlorothiazide due to its longer duration of action and proven cardiovascular disease reduction in trials 1
• Lisinopril attenuates the hypokalemia induced by thiazide diuretics 3

Special Considerations for Race

• For Black patients specifically, the combination of a calcium channel blocker plus thiazide diuretic may be more effective than calcium channel blocker plus ACE inhibitor 1

Monitoring After Adding Second Agent

• Check serum potassium and creatinine 2-4 weeks after adding either agent to detect potential electrolyte disturbances or changes in renal function 1
• Reassess blood pressure within 2-4 weeks after adding the second agent 1
• Target blood pressure should be <140/90 mmHg minimum, ideally <130/80 mmHg 1

If Blood Pressure Remains Uncontrolled on Dual Therapy

• If blood pressure remains above target after optimizing doses of both agents, add a third medication from the remaining class (if on ACE inhibitor + calcium channel blocker, add thiazide diuretic; if on ACE inhibitor + thiazide, add calcium channel blocker) to achieve guideline-recommended triple therapy 1
• The goal is to achieve target blood pressure within 3 months of initiating or modifying therapy 1

Critical Pitfalls to Avoid

• Do not combine lisinopril with an ARB, as this increases adverse events such as hyperkalemia and acute kidney injury without additional cardiovascular benefit 1
• Do not delay treatment intensification, as prompt action is required to reduce cardiovascular risk 1
• Confirm medication adherence before assuming treatment failure 1