What is the appropriate initial dose, titration schedule, and monitoring plan for lisinopril in an 86‑year‑old woman with uncontrolled hypertension?

Lisinopril for Uncontrolled Hypertension in an 86-Year-Old Woman

Start lisinopril 2.5 mg once daily and titrate gradually every 2–4 weeks to a target of 10–20 mg daily, monitoring renal function and potassium within 1–2 weeks of initiation and after each dose increase.

Initial Dosing Strategy

• Begin with lisinopril 2.5 mg once daily in this 86-year-old patient, as elderly patients require lower starting doses due to age-related pharmacokinetic changes and increased drug exposure 1, 2.
• The FDA-approved starting dose for elderly patients or those with potential renal impairment is 2.5–5 mg daily, but 2.5 mg is preferred in very elderly patients (>80 years) to minimize hypotension risk 1, 3.
• If baseline creatinine clearance is 10–30 mL/min, reduce the initial dose to 2.5 mg; if creatinine clearance is >30 mL/min, no dose adjustment is required, though starting conservatively is prudent in octogenarians 1, 4.

Titration Schedule

• Increase the dose every 2–4 weeks based on blood pressure response and tolerability, doubling the dose at each step: 2.5 mg → 5 mg → 10 mg → 20 mg once daily 5, 1.
• The target dose for hypertension is typically 10–20 mg daily, with a maximum of 40 mg daily if needed for blood pressure control 5, 1, 6.
• In elderly patients, 68–89% achieve adequate blood pressure control (diastolic ≤90 mmHg) with lisinopril 2.5–40 mg daily, and most respond to doses of 10–20 mg 2.
• Do not advance the dose if significant worsening of renal function or hyperkalemia occurs—see monitoring parameters below 5.

Monitoring Plan

Initial Assessment (Before Starting)

• Check baseline serum creatinine, estimated GFR, potassium, and sodium 5, 1.
• Measure sitting and standing blood pressure to assess for orthostatic hypotension risk 3.
• Verify the patient is not taking NSAIDs, potassium supplements, or potassium-sparing diuretics that increase hyperkalemia risk 5.

Early Monitoring (1–2 Weeks After Initiation)

• Recheck renal function (creatinine, GFR) and serum electrolytes (potassium, sodium) within 1–2 weeks of starting lisinopril 5, 1.
• Measure blood pressure at each visit during titration, targeting <130/80 mmHg (or at minimum <140/90 mmHg) 5.
• Assess for symptomatic hypotension (dizziness, lightheadedness), especially in the first few doses 5, 1.

After Each Dose Increase

• Recheck renal function and electrolytes 1 and 4 weeks after each dose escalation 5.
• An increase in creatinine up to 50% from baseline or to an absolute value of 265 µmol/L (3 mg/dL)—whichever is lower—is acceptable and reflects hemodynamic changes rather than tubular injury 5.
• If creatinine rises to 265–310 µmol/L (3.0–3.5 mg/dL), halve the lisinopril dose and monitor closely; if creatinine exceeds 310 µmol/L (3.5 mg/dL), stop lisinopril immediately 5.
• If potassium rises above 5.5 mmol/L, halve the lisinopril dose; if potassium exceeds 6.0 mmol/L, stop lisinopril and monitor closely 5.

Long-Term Monitoring (After Achieving Maintenance Dose)

• Recheck renal function and electrolytes at 1,3, and 6 months after achieving the maintenance dose, then every 6–12 months thereafter 5.
• Continue blood pressure monitoring at each visit, aiming for sustained control <130/80 mmHg 5.

Management of Common Adverse Effects

Symptomatic Hypotension

• Symptomatic hypotension (dizziness, lightheadedness) is common initially but often improves with time—reassure the patient 5.
• Consider reducing the dose of concurrent diuretics or other antihypertensive agents (except beta-blockers if indicated for heart failure or coronary disease) 5.
• Asymptomatic hypotension does not require intervention 5.

Worsening Renal Function

• Some rise in creatinine is expected and acceptable (up to 50% increase or to 265 µmol/L/3 mg/dL) 5.
• Check for nephrotoxic drugs (NSAIDs, aminoglycosides) and discontinue if possible 5.
• Do not stop lisinopril for modest creatinine increases (<50% rise) if the patient is otherwise stable, as ACE inhibitors provide long-term renal and cardiovascular protection 5.

Hyperkalemia

• Stop potassium supplements and potassium-sparing diuretics (amiloride, triamterene) if potassium rises 5.
• If hyperkalemia persists despite dose reduction, consider adding an SGLT2 inhibitor (if diabetic or heart failure is present), which reduces hyperkalemia risk and allows continuation of ACE inhibitor therapy 5.

Cough

• ACE inhibitor-induced cough occurs in 5–10% of patients and is a class effect 5.
• If cough is intolerable, switch to an angiotensin receptor blocker (ARB) such as valsartan 20 mg twice daily, titrated to 160 mg twice daily 5.

Adding a Diuretic if Blood Pressure Remains Uncontrolled

• If blood pressure is not controlled on lisinopril alone, add hydrochlorothiazide 12.5 mg once daily 1, 7.
• The combination of lisinopril plus hydrochlorothiazide produces greater blood pressure reduction than either agent alone (mean reduction -23.9/-18.2 mmHg vs. -16.6/-12.5 mmHg for lisinopril alone) 7.
• Lisinopril attenuates thiazide-induced hypokalemia, making the combination safer in elderly patients 6, 7.
• After adding a diuretic, it may be possible to reduce the lisinopril dose if hypotension or renal function changes occur 1.

Special Considerations in Very Elderly Patients

• Elderly patients (≥65 years) achieve similar blood pressure reductions to younger patients but may require lower doses (median effective dose 10–20 mg daily) 2, 3.
• Age-related differences in antihypertensive efficacy are not clinically significant, but elderly patients have higher rates of treatment discontinuation (though not clearly related to adverse events) 2.
• Start at the lowest dose (2.5 mg) and titrate slowly (every 2–4 weeks) to minimize hypotension and renal function changes 1, 2, 3.
• Postural hypotension is uncommon with lisinopril in elderly patients, but always measure standing blood pressure at baseline and during titration 3.

Common Pitfalls to Avoid

• Do not stop lisinopril for modest creatinine increases (<50% rise or <265 µmol/L/3 mg/dL), as this reflects hemodynamic changes and not tubular injury; stopping ACE inhibitors is associated with worse cardiovascular outcomes 5.
• Do not combine lisinopril with an ARB, as dual RAAS blockade increases adverse events (hyperkalemia, hypotension, acute kidney injury) without additional benefit 5.
• Do not use lisinopril in patients with bilateral renal artery stenosis or a solitary functioning kidney with renal artery stenosis, as ACE inhibitors can precipitate acute renal failure in these settings 5.
• Do not start lisinopril during acute decompensated heart failure or acute kidney injury—wait until clinical stabilization 5.
• Avoid NSAIDs (ibuprofen, naproxen, ketorolac), as they blunt the antihypertensive effect of ACE inhibitors and increase the risk of acute kidney injury and hyperkalemia 5.

Alternative if Lisinopril is Not Tolerated

• If the patient develops intolerable cough or angioedema, switch to an ARB such as valsartan 20 mg twice daily, titrated to 160 mg twice daily 5.
• ARBs have similar efficacy to ACE inhibitors for blood pressure control and cardiovascular protection but do not cause cough 5.
• ARBs carry the same risks of hyperkalemia, hypotension, and renal function changes as ACE inhibitors, so the same monitoring protocol applies 5.