What is a safe antihypertensive option for a patient with a cough?

Safe Antihypertensive Options for Patients with Cough

Switch to an angiotensin receptor blocker (ARB) as the first-line alternative antihypertensive for patients with cough, as ARBs provide equivalent cardiovascular benefits with a cough incidence similar to placebo (2-3%) compared to ACE inhibitors (7.9%). 1, 2

If the Cough is ACE Inhibitor-Induced

Immediate Management

• Discontinue the ACE inhibitor immediately - this is the only uniformly effective treatment for ACE inhibitor-induced cough, regardless of when the cough started relative to medication initiation 3, 1, 4
• Expect cough resolution within 1-4 weeks after stopping the medication, though it may take up to 3 months in some patients 3, 1, 2

Preferred Alternative: ARBs

• Start losartan 25 mg once daily as the most studied ARB for ACE inhibitor-induced cough, with proven efficacy showing cough rates of 17-29% (similar to placebo at 25-35%) versus 62-69% with ACE inhibitors 2, 5
• Titrate to 50 mg once daily if needed for blood pressure control 2
• Alternative ARBs include telmisartan (starting at 40 mg daily), candesartan (4-8 mg daily), or valsartan (20-40 mg twice daily) 1, 2
• ARBs do not inhibit ACE and therefore don't cause bradykinin accumulation, the mechanism responsible for ACE inhibitor-induced cough 1, 2, 4

Monitoring After ARB Switch

• Check blood pressure, renal function, and potassium within 1-2 weeks after initiation 2
• Monitor for postural blood pressure changes, especially in elderly patients 2
• Be aware that angioedema, though rare, can occur with ARBs in patients who previously experienced it with ACE inhibitors 2

If ARBs are Contraindicated or Not Tolerated

Calcium Channel Blockers as Second-Line

• Amlodipine 5 mg once daily is an excellent alternative, particularly for patients over 55 years old 1, 6
• Amlodipine has demonstrated ability to attenuate ACE inhibitor-induced cough in randomized controlled trials, with 61% of patients showing significant cough reduction 3, 1
• Amlodipine provides 24-hour blood pressure control with proven cardiovascular event reduction in large trials 7, 6
• Nifedipine 30 mg daily is another option, showing cough elimination or significant reduction in 51% of patients 3

Third-Line Options

• Thiazide-like diuretics can be considered if calcium channel blockers are not suitable 1

If ACE Inhibitor Must Be Continued

Pharmacologic Cough Suppression (Grade B Recommendation)

If there is a compelling reason to continue ACE inhibitor therapy, consider these suppressive agents 3, 1:

• Sodium cromoglycate: 10 mg inhaled four times daily for 14 days - showed reduction in 9/10 patients 3, 2
• Amlodipine: 5 mg once daily - eliminated cough in 6% and significantly reduced in 61% of patients 3
• Indomethacin: 50 mg twice daily for 14 days - eliminated in 27% and significantly reduced in 69% of patients 3
• Ferrous sulfate: 256 mg once daily for 28 days - 45% reduction in mean cough score 3

Important Caveat

• Approximately 30% of patients with confirmed ACE inhibitor-induced cough who were challenged and dechallenged twice did not develop cough after a third trial of ACE inhibitor therapy 3
• Therefore, a repeat trial of ACE inhibitor therapy may be attempted in patients with compelling indications after cough resolution 3

Key Clinical Pearls

• ACE inhibitor-induced cough occurs in 5-35% of patients and is more common in women and non-smokers 4
• The mechanism involves accumulation of bradykinin and substance P in the upper airway 3, 4
• All ARBs have equivalent cough profiles - no head-to-head trials show differences between specific ARBs 2
• Choice of ARB should be based on comorbidities, dosing convenience, and cost rather than cough profile 2
• Ensure the cough is not due to other common causes in elderly patients (heart failure, pulmonary disease, post-nasal drip) before attributing it to ACE inhibitors 4