In a patient on amlodipine 10 mg daily with uncontrolled hypertension in primary care, what medication should be added?

Adding Antihypertensive Medication to Amlodipine 10 mg

Add either an ACE inhibitor/ARB or a thiazide-like diuretic as your second agent to achieve guideline-recommended dual therapy for uncontrolled hypertension. 1

First-Line Add-On Options

ACE Inhibitor or ARB (Preferred for Most Patients)

• Start lisinopril 10 mg daily (titrate to 20–40 mg) or losartan 50 mg daily (titrate to 100 mg) to provide complementary mechanisms—vasodilation through calcium channel blockade plus renin-angiotensin system inhibition. 1

• This combination is particularly beneficial for patients with chronic kidney disease, heart failure, coronary artery disease, or diabetes, where RAS blockade offers additional organ protection beyond blood pressure reduction. 1

• The ACE inhibitor/ARB + amlodipine regimen may reduce amlodipine-related peripheral edema, a common side effect that leads to discontinuation. 1

• Monitor serum potassium and creatinine 2–4 weeks after initiating an ACE inhibitor or ARB to detect hyperkalemia or acute kidney injury. 1

Thiazide-Like Diuretic (Alternative or for Specific Populations)

• Start chlorthalidone 12.5–25 mg daily (preferred) or hydrochlorothiazide 25 mg daily if a diuretic is more appropriate for your patient. 1

• Chlorthalidone is superior to hydrochlorothiazide due to its longer duration of action (48–72 hours vs. 12–24 hours) and stronger cardiovascular outcome data from the ALLHAT trial. 1

• The amlodipine + thiazide combination is especially effective in elderly patients, Black patients, and those with volume-dependent hypertension. 1

• Check serum potassium and creatinine 2–4 weeks after starting a thiazide diuretic to detect hypokalemia or changes in renal function. 1

Special Population Considerations

Black Patients

• The combination of amlodipine plus a thiazide diuretic may be more effective than amlodipine plus an ACE inhibitor/ARB in Black patients, based on guideline recommendations. 1

Patients with Diabetes, CKD, or Heart Failure

• Prioritize adding an ACE inhibitor or ARB in patients with these comorbidities, as RAS blockade provides superior protection against progression of diabetic nephropathy and cardiovascular events. 1, 2

Blood Pressure Targets and Monitoring

• Target blood pressure is <140/90 mm Hg minimum for most patients, ideally <130/80 mm Hg for higher-risk individuals (diabetes, chronic kidney disease, established cardiovascular disease). 1

• Reassess blood pressure within 2–4 weeks after adding the second agent, with the goal of achieving target BP within 3 months of treatment modification. 1

Escalation to Triple Therapy (If Needed)

• If blood pressure remains ≥140/90 mm Hg after optimizing dual therapy, add the third agent from the remaining class (ACE inhibitor/ARB + amlodipine + thiazide diuretic) to create guideline-recommended triple therapy. 1

• This triple combination targets three complementary mechanisms: renin-angiotensin system blockade, vasodilation, and volume reduction. 1

Fourth-Line Agent for Resistant Hypertension

• If blood pressure remains uncontrolled on optimized triple therapy, add spironolactone 25–50 mg daily as the preferred fourth-line agent, which provides additional reductions of approximately 20–25/10–12 mm Hg. 1

• Monitor serum potassium closely when adding spironolactone to an ACE inhibitor or ARB, as the combination significantly increases hyperkalemia risk. 1

Critical Steps Before Adding Medication

• Verify medication adherence first—non-adherence is the most common cause of apparent treatment resistance. 1

• Confirm true hypertension with home blood pressure monitoring (≥135/85 mm Hg) or 24-hour ambulatory monitoring (≥130/80 mm Hg) to exclude white-coat hypertension. 1

• Review for interfering medications: NSAIDs, decongestants, oral contraceptives, systemic corticosteroids, and herbal supplements (ephedra, St. John's wort) can all elevate blood pressure. 1

• Screen for secondary hypertension if blood pressure remains severely elevated (≥180/110 mm Hg)—evaluate for primary aldosteronism, renal artery stenosis, obstructive sleep apnea, and pheochromocytoma. 1

Lifestyle Modifications (Adjunct to Pharmacotherapy)

• Sodium restriction to <2 g/day provides 5–10 mm Hg systolic reduction and enhances the efficacy of all antihypertensive classes, especially diuretics and RAS blockers. 1

• Weight loss of approximately 10 kg reduces blood pressure by about 6.0/4.6 mm Hg (systolic/diastolic). 1

• The DASH dietary pattern lowers blood pressure by roughly 11.4/5.5 mm Hg compared to a control diet. 1

• Regular aerobic exercise (≥30 minutes most days, approximately 150 minutes/week moderate intensity) reduces blood pressure by about 4/3 mm Hg. 1

• Limit alcohol intake to ≤2 drinks/day for men and ≤1 drink/day for women. 1

Common Pitfalls to Avoid

• Do not combine an ACE inhibitor with an ARB—dual RAS blockade increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 1

• Do not add a beta-blocker as the second agent unless there are compelling indications (angina, post-myocardial infarction, heart failure with reduced ejection fraction, atrial fibrillation requiring rate control)—beta-blockers are less effective than ACE inhibitors/ARBs or diuretics for stroke prevention in uncomplicated hypertension. 1

• Do not delay treatment intensification when blood pressure remains ≥140/90 mm Hg—prompt action within 2–4 weeks is required to reduce cardiovascular risk. 1

• Do not assume treatment failure without first confirming adherence and ruling out secondary causes or interfering substances. 1