How to Initiate and Titrate Oral Enalapril in an Elderly, ACE-Inhibitor-Naïve Patient with Hypertension and Possible Renal Impairment

Start with enalapril 2.5 mg once daily in this elderly patient with possible renal impairment, then titrate cautiously based on blood pressure response and renal function monitoring.

For elderly patients with suspected renal impairment (creatinine clearance ≤30 mL/min or serum creatinine ≥3 mg/dL), start enalapril at 2.5 mg once daily. 1
If renal function is preserved (creatinine clearance >30 mL/min), the standard starting dose is 5 mg once daily. 1
In patients currently on diuretics, discontinue the diuretic 2–3 days before starting enalapril if possible, or use an initial dose of 2.5 mg under medical supervision for at least 2 hours and until blood pressure stabilizes for an additional hour. 1

Observe the patient under medical supervision for at least 2 hours after the first dose, and continue monitoring until blood pressure has stabilized for at least an additional hour, as symptomatic hypotension may occur—especially in volume-depleted or diuretic-treated elderly patients. 1
If the patient is on a diuretic that cannot be discontinued, reduce the diuretic dose if possible before initiating enalapril to minimize hypotension risk. 1

Titrate enalapril upward every 4–7 days based on blood pressure response, increasing from 2.5 mg to 5 mg, then to 10 mg, and up to a maximum of 40 mg daily (given once daily or in two divided doses). 1, 2, 3
The usual maintenance dosage range for hypertension is 10–40 mg per day, administered in a single dose or two divided doses. 1
In patients treated once daily, if the antihypertensive effect diminishes toward the end of the dosing interval, consider increasing the dose or switching to twice-daily administration. 1

For patients with creatinine clearance >30 mL/min (serum creatinine up to approximately 3 mg/dL), use the standard 5 mg starting dose. 1
For patients with creatinine clearance ≤30 mL/min (serum creatinine ≥3 mg/dL), start at 2.5 mg once daily and titrate cautiously up to a maximum of 40 mg daily. 1
In dialysis patients, give 2.5 mg on dialysis days, and adjust dosing on non-dialysis days based on blood pressure response. 1
Enalapril can be safely administered to very elderly patients with progressive heart failure if the initial serum creatinine is below 1.9 mg/dL; above this threshold, careful monitoring and prompt discontinuation if renal function worsens can prevent irreversible renal damage. 4
Enalapril appears well-tolerated long-term in patients with severe renal impairment (serum creatinine >3 mg/dL), with similar adverse event rates compared to placebo. 5

Check serum creatinine and potassium 1–2 weeks after initiating enalapril and after each dose increase, especially in elderly patients with baseline renal impairment or those on diuretics. 6, 1
Monitor blood pressure 2–4 weeks after each dose adjustment, aiming to achieve target blood pressure <140/90 mmHg (or <130/80 mmHg for higher-risk patients) within 3 months. 6, 7
Watch for signs of hypotension (dizziness, lightheadedness, syncope), hyperkalemia, and worsening renal function, particularly during the first 4 days of therapy. 1, 4

If blood pressure is not controlled with enalapril alone, add a thiazide diuretic (preferred), calcium channel blocker, or beta-blocker as a second agent. 1, 8, 2, 3
The combination of enalapril with hydrochlorothiazide is particularly effective, with the ACE inhibitor attenuating the hypokalemic effect of the diuretic. 2, 3
Approximately 70% of patients respond to enalapril monotherapy with a diastolic blood pressure reduction ≥10 mmHg; adding a thiazide increases the response rate to >90%. 3
Avoid combining enalapril with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics, as this may lead to hyperkalemia. 1

Do not start with the standard 5 mg dose in elderly patients with suspected renal impairment or those on diuretics—use 2.5 mg to minimize hypotension and acute kidney injury risk. 1, 4
Do not assume treatment failure if blood pressure is not controlled on enalapril alone—most patients require combination therapy with a diuretic or calcium channel blocker. 8, 2, 3
Do not overlook the need for first-dose monitoring in elderly or volume-depleted patients, as symptomatic hypotension can occur within the first 2 hours. 1
Do not continue enalapril if serum creatinine rises significantly (e.g., >30% increase from baseline) without investigating for renovascular disease or volume depletion. 4, 5
Do not combine enalapril with an ARB, as dual renin-angiotensin system blockade increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 6, 7

In elderly patients (≥75 years), start at the lower end of the dosing range (2.5 mg) and titrate more slowly, as they are at higher risk for hypotension and renal impairment. 6, 4
In patients with heart failure and renal impairment (serum creatinine >1.6 mg/dL) or hyponatremia (serum sodium <130 mEq/L), initiate enalapril at 2.5 mg daily under close medical supervision, then titrate to 2.5 mg twice daily, then 5 mg twice daily, and higher as tolerated, usually at intervals of 4 days or more. 1
The maximum daily dose for heart failure is 40 mg in divided doses, with most patients in clinical trials titrated up to 20 mg twice daily. 1

Enalapril lowers blood pressure by reducing peripheral vascular resistance without increasing heart rate or cardiac output, making it particularly suitable for elderly patients. 8, 2
Enalapril is at least as effective as other ACE inhibitors, diuretics, beta-blockers, calcium antagonists, and alpha-blockers, but therapy may be less frequently limited by serious adverse effects or contraindications compared to other drug classes. 8
The most common adverse effects are dizziness, headache, and asthenia; serious adverse effects such as agranulocytosis, taste loss, rash, and proteinuria are rare with enalapril compared to sulfhydryl-containing ACE inhibitors like captopril. 2, 3
Cough is the most frequent adverse effect limiting ACE inhibitor therapy in clinical practice, occurring in approximately 6% of patients. 8