What additional antihypertensive medication should be added for a 76‑year‑old woman whose blood pressure remains 146/80 mm Hg despite one month of losartan 100 mg daily?

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

For this 76-year-old woman with blood pressure 146/80 mm Hg despite one month of losartan 100 mg daily, add either amlodipine 5 mg once daily or chlorthalidone 12.5 mg once daily as the second antihypertensive agent to achieve guideline-recommended dual therapy. 1

Why Combination Therapy Is Required Now

• Losartan 100 mg represents the maximum recommended daily dose for hypertension; doses above this have not demonstrated additional blood-pressure benefit and are primarily evaluated in heart-failure trials. 2, 3
• Adding a second agent from a different drug class produces an average systolic reduction of roughly 10–20 mm Hg, which is substantially larger than the effect of further dose escalation within the same class. 1
• The 2024 ESC and ACC/AHA guidelines explicitly recommend initiating combination therapy rather than up-titrating the ARB dose, because dual therapy provides complementary mechanisms and reaches blood-pressure goals more rapidly. 1

Choice of Second Agent

Option 1: Calcium-Channel Blocker (Preferred in Many Elderly Patients)

• Add amlodipine 5 mg once daily (can titrate to 10 mg after 2–4 weeks if needed). 1, 2
• The combination of an ARB with a calcium-channel blocker provides 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 and may lessen amlodipine-related peripheral edema when paired with an ARB. 1
• Dihydropyridine calcium-channel blockers do not cause bradycardia and are well-tolerated in elderly patients. 2
• Start with a low dose (2.5–5 mg) in patients ≥ 80 years and titrate gradually to minimize vasodilatory side effects. 2

Option 2: Thiazide-Like Diuretic

• Add chlorthalidone 12.5 mg once daily (preferred over hydrochlorothiazide due to longer duration of action and superior cardiovascular-outcome data from ALLHAT). 1
• The ARB + chlorthalidone combination is particularly effective in elderly patients, Black patients, and those with volume-dependent hypertension. 1
• The combination of an ARB with a thiazide diuretic attenuates HCTZ-induced hypokalemia, making it safer than diuretic monotherapy. 4
• Do not start with chlorthalidone doses above 12.5 mg in elderly patients, as doses above this significantly increase the risk of hypokalemia (3-fold higher risk), hypomagnesemia, and new-onset diabetes. 2

Blood-Pressure Targets and Monitoring

• Target blood pressure is <140/90 mm Hg minimum for most adults aged 60–79 years; for higher-risk patients (diabetes, chronic kidney disease, established cardiovascular disease), consider targeting <130/80 mm Hg if well-tolerated. 1, 2, 4
• For patients ≥ 80 years, a target of <140/90 mm Hg is appropriate if functionally independent; individualize based on frailty and tolerability. 2
• Re-measure blood pressure 2–4 weeks after adding the second agent, with the goal of achieving target blood pressure within 3 months of therapy modification. 1, 2, 4
• When a thiazide-type diuretic is introduced, check serum potassium and creatinine 2–4 weeks later to identify hypokalemia or renal impairment. 1, 4
• Monitor for orthostatic hypotension by checking blood pressure in both sitting and standing positions at each visit, as elderly patients have increased risk. 2, 4

Escalation to Triple Therapy (If Needed)

• If blood pressure remains ≥140/90 mm Hg after optimal dual therapy (losartan + amlodipine or losartan + chlorthalidone), add a third agent from the remaining class to create the triple regimen: ARB + calcium-channel blocker + thiazide diuretic. 1
• This triple combination, targeting renin-angiotensin blockade, vasodilation, and volume reduction, achieves blood-pressure control in >80% of patients. 1

Assessment Before Intensifying Therapy

• Verify medication adherence first (pill counts, pharmacy refill data, or direct questioning), as 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 effect. 1
• Review concomitant substances that can raise blood pressure: NSAIDs, decongestants, oral contraceptives, systemic corticosteroids, ephedra, licorice. 1

Lifestyle Modifications (Adjunctive to Pharmacotherapy)

• Sodium restriction to <2 g/day (≈5 g salt) yields an additional 5–10 mm Hg systolic reduction and enhances the effectiveness 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 mm Hg (systolic/diastolic). 1
• DASH dietary pattern (high in fruits, vegetables, whole grains, low-fat dairy; low in saturated fat) lowers blood pressure by roughly 11.4/5.5 mm Hg. 1
• Regular aerobic exercise (≥30 minutes most days, ≈150 minutes/week moderate intensity) reduces blood pressure by ≈4/3 mm Hg. 1
• Limit alcohol intake to ≤1 drink/day for women, as excess consumption interferes with blood-pressure control. 1

Critical Pitfalls to Avoid

• 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, 4
• Do not add a beta-blocker as the second agent unless there is a compelling indication (e.g., angina, post-myocardial infarction, heart failure with reduced ejection fraction, or atrial fibrillation requiring rate control); beta-blockers are less effective than calcium-channel blockers or diuretics for stroke prevention in uncomplicated hypertension. 1
• Do not delay treatment intensification when blood pressure stays ≥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, excluding white-coat hypertension, and ruling out secondary causes or interfering substances. 1
• Do not use non-dihydropyridine calcium-channel blockers (diltiazem, verapamil) in patients with left ventricular dysfunction or heart failure because of their negative inotropic effects. 1