What are the recommendations for a patient who develops a cough after starting lisinopril (angiotensin-converting enzyme inhibitor) for hypertension?

Management of Lisinopril-Induced Cough

For a patient who develops cough after starting lisinopril for hypertension, the recommended approach is to switch to an angiotensin receptor blocker (ARB), which provides similar antihypertensive efficacy without the cough side effect. 1, 2

Understanding ACE Inhibitor-Induced Cough

• ACE inhibitor-induced cough is a common side effect occurring in approximately 10-20% of patients, typically presenting as a dry, persistent cough that begins within days to weeks after starting the medication 2
• The cough is caused by the accumulation of bradykinin and substance P when ACE is inhibited, not by the blood pressure-lowering effect of the medication 2
• Diagnosis is confirmed by resolution of cough after discontinuation of the ACE inhibitor, usually within 1-4 weeks (though it may take up to 3 months in some cases) 1, 2

Management Algorithm

Step 1: Discontinue the ACE Inhibitor

• Discontinuing the ACE inhibitor is the only uniformly effective treatment for ACE inhibitor-induced cough 1, 2
• The cough typically resolves within 1-4 weeks after stopping the medication, though it may take up to 3 months in some patients 1

Step 2: Switch to an ARB

• ARBs are the preferred alternative for patients with ACE inhibitor-induced cough as they do not inhibit ACE and therefore don't cause bradykinin accumulation 2, 3
• Clinical guidelines strongly recommend (Grade A recommendation) switching to an ARB when ACE inhibitor-induced cough occurs 1, 3
• ARBs have a similar incidence of cough as placebo and significantly lower than ACE inhibitors in patients with a history of ACE inhibitor-induced cough 4, 5, 6

Step 3: ARB Selection and Dosing

• Losartan is the most studied ARB for patients with ACE inhibitor-induced cough, with a starting dose of 25mg once daily 3, 6
• Other options include:
  • Valsartan: 80mg once daily has been shown to cause significantly less cough than lisinopril in patients with a history of ACE inhibitor-induced cough 4
  • Candesartan: 8mg once daily has demonstrated cough incidence similar to placebo and lower than enalapril 5

Step 4: Monitoring

• Monitor blood pressure, renal function, and potassium within 1-2 weeks after initiation of the ARB 3
• Assess for adequate blood pressure control and adjust dosing as needed 3

Special Considerations

• While rare, cough has been reported with ARBs in some cases, though the incidence is significantly lower than with ACE inhibitors 7
• If ARBs are contraindicated or not tolerated, consider a calcium channel blocker (CCB) as an alternative, particularly for patients over 55 years old 2
• Thiazide-like diuretics can also be considered if CCBs are not suitable 2
• For this 50-year-old female patient with BP 135/102, headaches, and blurred vision, prompt control of blood pressure is important to reduce risk of complications 2

Pitfalls to Avoid

• Do not attempt to suppress the cough with antitussives while continuing the ACE inhibitor, as this approach is less effective than switching to an ARB 1
• Do not rechallenge with another ACE inhibitor as the cough is a class effect, with studies showing varying but significant incidence across different ACE inhibitors (enalapril 7%, captopril 5.1%, perindopril 2.2%, and lisinopril 1.6%) 8
• Avoid delaying the switch to an alternative medication, as persistent cough can negatively impact quality of life and medication adherence 1, 2