What changes should be made to a patient's antihypertensive regimen, currently on lisinopril (angiotensin-converting enzyme inhibitor) 40mg po, chlorthalidone (diuretic), carvedilol (beta blocker), hydralazine (vasodilator), and other medications, who develops a persistent dry cough after increasing lisinopril from 5mg?

Discontinue Lisinopril and Switch to an Angiotensin Receptor Blocker (ARB)

The lisinopril should be discontinued immediately and replaced with an ARB such as valsartan or losartan, as this is the only uniformly effective treatment for ACE inhibitor-induced cough, with the cough typically resolving within 1-4 weeks after cessation. 1, 2, 3

Understanding the Clinical Problem

The persistent dry cough is almost certainly caused by the lisinopril, not the dose increase itself, as ACE inhibitor-induced cough is:

• Not dose-dependent - it occurs as a class effect regardless of dosage 1, 3
• Present in 5-35% of patients taking ACE inhibitors 1, 2
• More common in women and non-smokers 1, 2
• Can develop within hours to months after starting therapy 1, 2

The fact that the cough appeared after increasing from 5mg to 40mg is coincidental timing; the patient likely would have developed this cough at any dose. 1

Specific Management Steps

Step 1: Discontinue Lisinopril Immediately

• Stop the lisinopril 40mg completely 1, 2, 3
• The American College of Chest Physicians provides a Grade B recommendation for immediate discontinuation as the only uniformly effective treatment 1, 3
• Expect cough resolution within 1-4 weeks, though it may take up to 3 months in some patients 1, 2

Step 2: Wait 36 Hours Before Starting ARB

• Allow at least 36 hours between the last lisinopril dose and initiating the ARB 2
• This washout period minimizes the risk of adverse effects from overlapping therapy 2

Step 3: Initiate ARB Therapy

Switch to an ARB with Class I, Level A recommendation (highest level of evidence): 2, 3

Valsartan dosing:

• Start at 20-40 mg twice daily 2
• Titrate up to 160 mg twice daily for optimal therapeutic effect 2

Alternative ARB options with proven low cough incidence:

• Candesartan 8mg once daily 4
• Telmisartan 80mg once daily 5
• Losartan (standard ARB alternative) 3

Step 4: Monitor After the Switch

• Check blood pressure, renal function, and potassium levels within 1-2 weeks after initiating the ARB 2, 3
• Reassess cough status at 3-4 weeks to confirm resolution 2

Evidence Supporting ARB Switch

ARBs have dramatically lower cough incidence compared to ACE inhibitors:

• Valsartan causes cough in only 19.5% vs 68.9% with lisinopril in patients with prior ACE inhibitor-induced cough 6
• Candesartan causes cough in 35.5% vs 68.2% with enalapril (similar to placebo at 26.9%) 4
• Telmisartan causes cough in 15.6% vs 60% with lisinopril (comparable to placebo at 9.7%) 5

Other Medications to Continue

No changes needed to the other antihypertensives:

• Continue chlorthalidone (diuretic) 2, 7
• Continue carvedilol (beta-blocker) - do not discontinue when switching from ACE inhibitor to ARB, as both are essential components of guideline-directed therapy 7
• Continue hydralazine (vasodilator) 2

All other medications can continue unchanged:

• Tamsulosin, rosuvastatin, rivaroxaban, methocarbamol, melatonin, trazodone, and loperamide are not contributing to the cough 1

Critical Pitfalls to Avoid

• Do not try alternative ACE inhibitors - cough is a class effect and will recur with any ACE inhibitor (captopril, enalapril, ramipril, etc.) 1, 8, 9
• Do not reduce the lisinopril dose - the cough is not dose-dependent and will persist at any dosage 1, 3
• Do not pursue extensive cough workup before discontinuing lisinopril - this wastes time and resources when the diagnosis is clear 2
• Do not discontinue the beta-blocker when making the ACE inhibitor to ARB switch 7
• Do not start the ARB immediately - wait the full 36 hours after the last lisinopril dose 2