What first-line antihypertensive medication can be used as an alternative to lisinopril (Angiotensin-Converting Enzyme Inhibitor, ACEI) in a patient experiencing a dry cough?

Alternative Antihypertensive Medication for Patient with ACE Inhibitor-Induced Cough

For a patient experiencing dry cough associated with lisinopril use for 4 months, an angiotensin receptor blocker (ARB) should be prescribed as the first-line alternative antihypertensive medication.

Understanding ACE Inhibitor-Induced Cough

Persistent dry cough is a well-documented side effect of ACE inhibitors like lisinopril. This cough:

• Occurs in approximately 5-35% of patients taking ACE inhibitors
• Is due to the accumulation of bradykinin and substance P resulting from ACE inhibition 1
• Typically resolves within 1-4 weeks after discontinuation, though may take up to 3 months in some cases 1

Management Algorithm for ACE Inhibitor-Induced Cough

Step 1: Confirm and Discontinue

• Discontinue lisinopril regardless of the temporal relationship between cough onset and medication initiation 1
• The diagnosis is confirmed when cough resolves after discontinuation 1

Step 2: Select Alternative First-Line Agent

• Angiotensin Receptor Blockers (ARBs) are the preferred alternative:
  • ARBs do not inhibit ACE and therefore do not increase bradykinin levels 1
  • Clinical trials demonstrate ARBs have cough incidence similar to placebo 1, 2
  • Losartan showed cough incidence of only 17% compared to 69% with lisinopril in patients with history of ACE inhibitor-induced cough 2
  • Telmisartan demonstrated cough incidence of 15.6% compared to 60% with lisinopril and 9.7% with placebo 3

Step 3: If ARBs Are Contraindicated or Not Tolerated

Consider other first-line antihypertensive agents:

• Calcium channel blockers like amlodipine 4
• Thiazide or thiazide-like diuretics like hydrochlorothiazide or chlorthalidone 5

Evidence Quality and Recommendations

The recommendation to switch to an ARB is supported by high-quality evidence:

• ACCP evidence-based clinical practice guidelines give this a Grade A recommendation (Quality of evidence: good; net benefit: substantial) 1
• FDA labeling for losartan confirms significantly lower cough incidence compared to ACE inhibitors 2

Important Considerations and Caveats

1. Rare cases of ARB-induced cough: While uncommon, there have been isolated case reports of cough with ARBs 6. Monitor the patient after switching.

2. Timing of resolution: Inform the patient that cough may take up to 4 weeks to resolve after discontinuing lisinopril, though in some cases it may persist for up to 3 months 1.

3. Compelling indications: If there is a compelling reason to use an ACE inhibitor (e.g., heart failure with reduced ejection fraction, diabetic nephropathy), consider:

   • A trial of pharmacologic therapy to suppress cough while continuing ACE inhibitor (sodium cromoglycate, theophylline, amlodipine, nifedipine) 1
   • A repeat trial of ACE inhibitor therapy if cough resolves after initial discontinuation 1

4. Blood pressure monitoring: Ensure close monitoring of blood pressure after switching medications to confirm adequate control.

Bottom Line

For a 55-year-old male with dry cough for 4 months while on lisinopril, an ARB (such as losartan, telmisartan, or candesartan) is the most appropriate alternative first-line antihypertensive medication based on strong evidence showing similar efficacy to ACE inhibitors with significantly lower risk of cough.