What antihypertensive medication should be added for a 46‑year‑old adult with stage‑2 hypertension (blood pressure 180/95 mm Hg) who is already taking losartan 100 mg daily?

Add a Calcium Channel Blocker or Thiazide Diuretic to Losartan 100 mg

For a 46-year-old with stage 2 hypertension (180/95 mmHg) on losartan 100 mg, you should add either amlodipine 5–10 mg daily OR chlorthalidone 12.5–25 mg daily as the second agent to achieve guideline-recommended dual therapy. 1

Why Combination Therapy Over Dose Escalation

• Stage 2 hypertension (≥160/100 mmHg) requires prompt treatment with two antihypertensive agents from different classes rather than monotherapy dose escalation. 1
• Losartan 100 mg is already the maximum recommended dose for hypertension; further dose increases provide minimal additional blood pressure reduction (only ≈1.6/3.3 mmHg). 2
• Adding a second agent from a different class yields substantially larger systolic reductions of 10–20 mmHg and reaches target blood pressure faster than uptitrating losartan alone. 2

First-Line Add-On Option: Calcium Channel Blocker

• Amlodipine 5–10 mg once daily creates the guideline-endorsed ARB + CCB regimen, providing complementary vasodilation through calcium-channel blockade together with renin-angiotensin inhibition. 1
• This combination is especially advantageous in patients with chronic kidney disease, diabetes, coronary artery disease, or heart failure. 1
• The ARB + CCB combination may attenuate amlodipine-related peripheral edema when paired with an angiotensin receptor blocker. 1

Alternative Add-On Option: Thiazide-Like Diuretic

• Chlorthalidone 12.5–25 mg once daily (preferred) or hydrochlorothiazide 25 mg daily yields an ARB + diuretic regimen that addresses volume-dependent hypertension. 1
• Chlorthalidone is favored over hydrochlorothiazide because of its longer duration of action (24–72 hours vs 6–12 hours) and superior cardiovascular outcome data from the ALLHAT trial. 1
• The ARB + chlorthalidone combination is particularly effective in elderly patients, Black patients, and those with volume-dependent hypertension. 1

Blood Pressure Targets and Monitoring

• Target blood pressure is <130/80 mmHg for most adults; at minimum <140/90 mmHg. 1
• Re-measure blood pressure 2–4 weeks after adding the second agent, with the goal of achieving target within 3 months of the therapeutic change. 1
• Check serum potassium and creatinine 2–4 weeks after initiating a thiazide diuretic to detect hypokalemia or renal impairment. 1

Escalation to Triple Therapy (If Needed)

• If blood pressure remains uncontrolled on ARB + CCB or ARB + diuretic, add the third agent from the remaining class to form triple therapy (ARB + CCB + diuretic). 1
• Triple therapy achieves control in >80% of patients with stage 2 hypertension. 1
• When optimized triple therapy still leaves blood pressure ≥140/90 mmHg, add spironolactone 25–50 mg daily as the preferred fourth-line agent for resistant hypertension. 1

Critical Steps Before Adding Medication

• Verify medication adherence first—non-adherence is the most common cause of apparent treatment resistance (use pill counts, pharmacy refill data, or direct questioning). 1
• Confirm true hypertension with home blood pressure monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) before escalating therapy. 1
• Review for interfering substances: NSAIDs, decongestants, oral contraceptives, systemic corticosteroids, stimulants, herbal supplements (ephedra, licorice) that can raise blood pressure. 1

Lifestyle Modifications (Adjunct to Pharmacotherapy)

• Sodium restriction to <2 g/day (≈5 g salt) yields a 5–10 mmHg systolic reduction and augments the efficacy of all antihypertensive classes, especially diuretics and ARBs. 1
• Weight loss for individuals with BMI ≥25 kg/m²—losing ≈10 kg reduces blood pressure by about 6/4.6 mmHg (systolic/diastolic). 1
• Adoption of the DASH dietary pattern lowers blood pressure by roughly 11.4/5.5 mmHg. 1
• Regular aerobic exercise (≥30 minutes most days, ≈150 minutes/week moderate intensity) reduces blood pressure by ≈4/3 mmHg. 1
• Limit alcohol intake to ≤2 drinks/day for men and ≤1 drink/day for women. 1

Common Pitfalls to Avoid

• Do not add a beta-blocker as the second agent unless there is a compelling indication (angina, post-myocardial infarction, heart failure with reduced ejection fraction, atrial fibrillation requiring rate control); beta-blockers are less effective than CCBs or diuretics for stroke prevention in uncomplicated hypertension. 1
• Do not combine losartan with an ACE inhibitor (dual renin-angiotensin blockade) because it increases the risk of hyperkalemia, acute kidney injury, and hypotension without added cardiovascular benefit. 1
• Do not delay treatment intensification when blood pressure remains ≥160/100 mmHg; prompt action within 2–4 weeks is required to reduce cardiovascular risk. 1
• Do not assume treatment failure without first confirming adherence, excluding white-coat hypertension, and ruling out secondary causes or interfering substances. 1