What alternative antihypertensive medication can be prescribed for a 72‑year‑old woman who develops a cough while taking lisinopril?

Switch to an Angiotensin Receptor Blocker (ARB)

Discontinue lisinopril immediately and switch to an angiotensin receptor blocker (ARB), as this is the guideline-recommended first-line alternative for ACE inhibitor-induced cough, providing equivalent cardiovascular benefits without causing bradykinin accumulation—the mechanism responsible for the cough. 1

Why ARBs Are the Preferred Alternative

• ARBs do not inhibit ACE and therefore do not cause accumulation of bradykinin and substance P, the mediators responsible for ACE inhibitor-induced cough 2
• Cough incidence with ARBs is dramatically lower than ACE inhibitors and similar to placebo (approximately 2-3% vs 7.9% with ACE inhibitors) 3
• Clinical trial data confirms superior tolerability: In controlled trials, losartan caused cough in only 17-29% of patients with prior ACE inhibitor-induced cough, compared to 62-69% who developed cough when rechallenged with lisinopril 4
• Cardiovascular benefits are equivalent to ACE inhibitors, making ARBs an appropriate substitution without compromising efficacy 1, 5

Specific ARB Recommendations and Dosing

First-Line Option: Losartan

• Start with losartan 25-50 mg once daily for this 72-year-old female patient 3
• Titrate to 100 mg once daily if blood pressure remains ≥140/90 mm Hg after 2-4 weeks and the medication is well-tolerated 1, 3
• Losartan is the most extensively studied ARB for patients with ACE inhibitor-induced cough 3

Alternative ARB Options

• Candesartan 8 mg once daily, titrating to 32 mg once daily as needed, with demonstrated cough incidence (35.5%) significantly lower than enalapril (68.2%) 1
• Valsartan 40-80 mg once daily, titrating to 160 mg twice daily as needed, with cough incidence of only 19.5% versus lisinopril 68.9% 1, 6

Implementation Strategy

Immediate Steps

• Discontinue lisinopril today as cessation is the only uniformly effective treatment for ACE inhibitor-induced cough 2, 5
• Start the ARB immediately without a washout period 1
• Inform the patient that cough should resolve within 1-4 weeks, though it may take up to 3 months in some cases 2

Monitoring Requirements

• Check baseline renal function and potassium before starting ARB therapy 1
• Reassess blood pressure, renal function, and potassium within 1-2 weeks after ARB initiation 1, 3
• Monitor blood chemistry at 4-month intervals thereafter 1
• Pay particular attention to postural blood pressure changes in this elderly patient 3

Safety Considerations and Acceptable Parameters

Renal Function Monitoring

• Creatinine increases up to 50% above baseline or 266 μmol/L (3 mg/dL) are acceptable 1
• If creatinine increases by >100%, seek specialist advice 1

Potassium Management

• Potassium levels up to 5.5 mmol/L are acceptable 1
• If potassium rises above 5.5 mmol/L, halve the ARB dose and recheck within 1-2 weeks 1
• If potassium exceeds 6.0 mmol/L, seek specialist advice 1

Blood Pressure Targets

• Asymptomatic hypotension does not require dose adjustment 1
• For symptomatic hypotension, reconsider need for other vasodilators and reduce diuretic dose if no signs of congestion 1

Critical Warnings

Angioedema Risk

• Although rare (<1%), angioedema can occur with ARBs in patients who previously experienced angioedema with ACE inhibitors 1, 3
• Use caution during initial ARB treatment and monitor closely 1
• If angioedema occurs with an ARB, discontinue immediately and avoid all ARBs for the patient's lifetime 1

Common Pitfalls to Avoid

• Do not assume all cough is ACE inhibitor-related—exclude pulmonary edema and other respiratory causes before attributing cough to lisinopril 1
• Do not combine ARBs with both ACE inhibitors and aldosterone antagonists, as this increases risk of hyperkalemia and renal dysfunction 1
• Do not stop concomitant nephrotoxic drugs (NSAIDs) or potassium supplements without first assessing for signs of congestion 1
• Avoid abrupt withdrawal of renin-angiotensin system inhibition, as clinical deterioration is likely 1

Special Considerations for This 72-Year-Old Female Patient

• Women have higher rates of ACE inhibitor-induced cough than men (this patient fits the typical profile) 2
• Elderly patients require careful dose titration when initiating new antihypertensive therapy 5
• Start with lower ARB doses and titrate slowly in elderly patients 5
• Blood pressure targets may be less aggressive in elderly patients to avoid adverse effects 5

Alternative if ARBs Are Not Tolerated

Calcium Channel Blockers

• Consider amlodipine 5 mg once daily if ARBs are contraindicated or not tolerated, as calcium channel blockers have demonstrated ability to attenuate ACE inhibitor-induced cough in randomized controlled trials 2, 5, 3
• Amlodipine showed significant cough reduction in 61% of patients who continued ACE inhibitor therapy 3