What is the most appropriate additional antihypertensive medication for a 70‑year‑old man with isolated systolic hypertension (194/87 mm Hg) who is already taking candesartan 8 mg daily and is asymptomatic?

Add a Dihydropyridine Calcium Channel Blocker to His Current Regimen

For this 70-year-old man with isolated systolic hypertension (194/87 mmHg) on candesartan 8 mg, add amlodipine 5 mg once daily as the next step. 1, 2

Rationale for This Recommendation

Why a Calcium Channel Blocker?

• Thiazide diuretics and dihydropyridine calcium channel blockers (CCBs) are the only drug classes with robust randomized trial evidence demonstrating cardiovascular mortality reduction specifically in isolated systolic hypertension in elderly patients. 1
• The European Society of Cardiology guidelines establish that randomized trials targeting isolated systolic hypertension have shown outcome benefit with thiazides and calcium antagonists, making them first-line agents. 3
• In this patient already on an ARB (candesartan), adding a CCB provides complementary mechanism of action and is the preferred combination strategy. 1, 4

Why Not Simply Uptitrate Candesartan First?

• While candesartan can be increased from 8 mg to 16 mg or 32 mg 5, the patient's blood pressure of 194/87 mmHg represents stage 2 hypertension requiring immediate dual therapy rather than sequential monotherapy titration. 1
• Combination therapy achieves target blood pressure faster and with better tolerability than maximizing single agents. 1
• The maximal antihypertensive effect of any candesartan dose requires 4 weeks 5, and this patient needs more aggressive control given the systolic pressure of 194 mmHg.

Why Amlodipine Specifically?

• Start amlodipine at 5 mg once daily (can begin at 2.5 mg in very frail elderly, but this 70-year-old asymptomatic patient tolerates standard dosing). 1, 2
• Dihydropyridine CCBs demonstrate particular efficacy in isolated systolic hypertension, which is characterized by the wide pulse pressure (107 mmHg) seen in this patient. 6, 4
• Amlodipine does not cause bradycardia and is well-tolerated in elderly patients. 2

Alternative: Add a Thiazide-Like Diuretic

• If CCBs are contraindicated or not tolerated, add chlorthalidone 12.5 mg daily or indapamide 1.25 mg daily. 1, 2
• Thiazide-like diuretics have the strongest outcome evidence for isolated systolic hypertension in adults >60 years, showing absolute risk reductions of 1.13% for stroke and 1.64% for mortality. 1
• However, monitor electrolytes 2-4 weeks after initiation, as elderly patients have 3-fold higher risk of hypokalemia with chlorthalidone, and hypokalemia below 3.5 mEq/L eliminates cardiovascular protection. 2

Blood Pressure Target

• Aim for systolic blood pressure <140 mmHg and diastolic <90 mmHg as the minimum target. 1
• If well-tolerated and the patient has high cardiovascular risk (which age 70 confers), consider targeting systolic 120-129 mmHg. 1
• The diastolic pressure of 87 mmHg is acceptable; avoid excessive diastolic lowering below 60 mmHg, which may increase risk in patients with coronary disease. 3

Monitoring Strategy

• Measure blood pressure in both sitting and standing positions to detect orthostatic hypotension, which is common in elderly patients. 3, 1, 2
• Recheck blood pressure within 2-4 weeks of adding amlodipine. 2
• If blood pressure remains ≥140/90 mmHg after 4 weeks on dual therapy, uptitrate amlodipine to 10 mg daily. 1, 2
• If still uncontrolled on candesartan plus maximal CCB, add a thiazide-like diuretic as third-line therapy. 1

Critical Pitfalls to Avoid

• Do not delay treatment intensification because the patient is asymptomatic—isolated systolic hypertension causes silent cardiovascular damage. 1
• Do not add a beta-blocker, as they are less effective than CCBs or diuretics for stroke prevention in elderly patients with isolated systolic hypertension. 1, 2
• Do not use chlorthalidone doses above 12.5-25 mg, as higher doses significantly increase hypokalemia risk without additional blood pressure benefit. 2
• Do not ignore standing blood pressure measurements—failure to check for orthostatic hypotension increases fall risk. 1, 2

Evidence Supporting Candesartan Plus CCB Combination

• Research demonstrates that candesartan and hydrochlorothiazide have additive effects in isolated systolic hypertension, with candesartan being more effective than hydrochlorothiazide as monotherapy. 7
• In elderly patients with isolated systolic hypertension, candesartan 16-32 mg produces dose-related systolic blood pressure reduction with substantial pulse pressure decrease. 8
• The combination of an ARB with a CCB or thiazide diuretic is specifically recommended when compelling indications such as the patient's age and cardiovascular risk coexist. 4