In a 79‑year‑old patient with hypertension already on amlodipine 5 mg, is it preferable to increase amlodipine to 10 mg and start enalapril 2.5 mg rather than adding enalapril 5 mg directly?

Dose Titration Strategy for Enalapril in Elderly Hypertensive Patients

In a 79-year-old patient already on amlodipine 5 mg with uncontrolled hypertension, start enalapril at 2.5 mg daily rather than 5 mg directly, then titrate the amlodipine to 10 mg before increasing enalapril further. This approach minimizes first-dose hypotension risk while optimizing the existing calcium channel blocker therapy first.

Rationale for Low-Dose ACE Inhibitor Initiation in the Elderly

Elderly patients are significantly more susceptible to first-dose hypotension with ACE inhibitors due to decreased renal clearance, impaired cardiovascular reflexes, and altered pharmacokinetics that result in higher plasma concentrations of active drug. 1

• Although standard dosages are often well tolerated, hypotensive reactions in elderly patients are unpredictable, making lower initial dosages (2.5 mg enalapril) safer than starting at 5 mg. 1
• The maintenance dosage should be titrated upward based on blood pressure response and tolerability, not predetermined by age alone. 1
• Elderly patients with concurrent conditions require even more cautious introduction of ACE inhibitors, with close supervision during initial dosing. 1

Optimizing Existing Amlodipine Therapy First

Before escalating enalapril beyond 2.5 mg, increase amlodipine from 5 mg to 10 mg to maximize the calcium channel blocker component of dual therapy. 2

• Amlodipine produces dose-dependent blood pressure reductions, with 10 mg providing significantly greater efficacy than 5 mg in elderly Chinese patients (mean reduction -20.8/-9.2 mm Hg at 10 mg). 3
• The combination of amlodipine and enalapril has demonstrated superior blood pressure control compared to either agent alone, with a total effective rate of 87.5% versus 59.6% for amlodipine monotherapy in elderly patients. 4
• Amlodipine maintains most of its antihypertensive effect for 72 hours after the last dose, providing protection against missed doses—particularly important in elderly patients. 3

Stepwise Titration Algorithm

Follow this specific sequence:

1. Week 0-2: Start enalapril 2.5 mg once daily while continuing amlodipine 5 mg. Monitor blood pressure after 1-2 weeks and assess for orthostatic hypotension, dizziness, or excessive blood pressure reduction. 1

2. Week 2-4: If blood pressure remains ≥140/90 mm Hg and the patient tolerates enalapril 2.5 mg without hypotensive symptoms, increase amlodipine to 10 mg daily before increasing enalapril. 2, 3

3. Week 4-8: Reassess blood pressure. If still ≥140/90 mm Hg on amlodipine 10 mg plus enalapril 2.5 mg, increase enalapril to 5 mg daily. 2

4. Week 8-12: If blood pressure remains uncontrolled, continue titrating enalapril up to 10-20 mg daily as tolerated, or add a thiazide-like diuretic (chlorthalidone 12.5-25 mg) as the third agent. 2

Evidence Supporting Combination Efficacy

The amlodipine-enalapril combination provides complementary mechanisms—vasodilation through calcium channel blockade and renin-angiotensin system inhibition—resulting in superior blood pressure control compared to either agent alone. 4, 5, 6

• In moderate-to-severe hypertension, adding amlodipine 10 mg to enalapril produced significantly larger reductions in mean blood pressure than enalapril plus placebo, with good tolerability. 5
• A 50-week comparative trial demonstrated that both amlodipine (5-10 mg) and enalapril (10-40 mg) were similarly effective in lowering blood pressure while maintaining quality of life, with few clinically significant adverse effects. 6
• The combination is effective and well tolerated when administered as add-on therapy, with side effects generally mild or moderate. 5

Monitoring Requirements

Check blood pressure within 2-4 weeks after each dose adjustment, targeting <140/90 mm Hg minimum (ideally <130/80 mm Hg if well tolerated). 2

• Monitor serum potassium and creatinine 2-4 weeks after initiating or increasing enalapril, especially when combined with other agents. 2
• Assess for orthostatic hypotension at each visit by measuring blood pressure supine and after 1-3 minutes of standing. 1
• Evaluate for ACE inhibitor-related cough, which occurred in 15% of patients in one study, though this was less common with amlodipine (0% treatment-related cough). 3

Critical Pitfalls to Avoid

Do not start enalapril at 5 mg in a 79-year-old patient without first assessing tolerability at 2.5 mg, as this increases the risk of symptomatic hypotension that may lead to falls, syncope, or medication discontinuation. 1

• Do not combine enalapril with an ARB (dual RAS blockade), as this increases adverse events including hyperkalemia and acute kidney injury without additional cardiovascular benefit. 2
• Do not delay treatment intensification beyond 2-4 weeks if blood pressure remains uncontrolled, as prompt action is required to reduce cardiovascular risk. 2
• Do not assume treatment failure without first confirming medication adherence and ruling out secondary causes of hypertension or interfering medications (NSAIDs, decongestants). 2