What is the best approach to evaluate and manage a persistent dry cough in a patient with chronic heart failure, who is being treated with Jardiance (empagliflozin), metoprolol, diuretics, and Elaquis (apixaban)?

Evaluation and Management of Persistent Dry Cough in Heart Failure Patients

The most likely cause of persistent dry cough in this patient is the medication "Entrust" (sacubitril/valsartan), which contains an ACE inhibitor component that commonly causes dry cough; however, you should first rule out worsening heart failure with pulmonary congestion before attributing the cough to medication. 1

Initial Assessment: Rule Out Cardiac Causes

Before treating the cough symptomatically or changing medications, you must exclude pulmonary edema as the underlying cause, especially when a new or worsening cough develops in heart failure patients 1. Specifically assess for:

• Signs of volume overload: peripheral edema, jugular venous distension, orthopnea, paroxysmal nocturnal dyspnea 1
• Chest radiograph findings: pulmonary congestion, pleural effusions 2
• Weight changes: sudden weight gain suggesting fluid retention 1

If pulmonary edema is present, optimize diuretic therapy rather than treating the cough symptomatically 1.

Medication-Induced Cough Evaluation

ACE Inhibitor/ARB-Related Cough

The medication "Entrust" likely refers to sacubitril/valsartan (Entresto), which contains valsartan (an ARB). While ARBs cause significantly less cough than ACE inhibitors 2, they can still cause cough in some patients. However, this is much less common than with ACE inhibitors 2.

• If the patient was previously on an ACE inhibitor and switched to sacubitril/valsartan: The cough may be residual from prior ACE inhibitor therapy, which can persist for weeks after discontinuation 1
• ACE inhibitor-induced cough rarely requires treatment discontinuation 1

Other Medications Assessment

The other medications in this regimen are unlikely culprits:

• Jardiance (empagliflozin): Not associated with cough 3, 4, 5, 6
• Metoprolol: Not a common cause of dry cough 2
• Diuretics: Not associated with dry cough 2
• Eliquis (apixaban): Not associated with cough

Systematic Evaluation for Common Causes

Once cardiac causes are excluded, evaluate for the three most common causes of chronic cough in descending order of prevalence 2:

1. Upper Airway Cough Syndrome (UACS)

• Empiric trial with first-generation antihistamine/decongestant combination 2
• Caution: Avoid sympathomimetic decongestants as they can increase blood pressure and heart rate, potentially worsening heart failure 1
• Safer alternative: Saline nasal sprays for post-nasal drip without systemic effects 1

2. Asthma/Bronchial Hyperresponsiveness

• Consider empiric trial of inhaled corticosteroids if UACS treatment fails 2
• Use spacer devices with metered-dose inhalers to optimize drug delivery while minimizing systemic absorption 1

3. Gastroesophageal Reflux Disease (GERD)

• Trial of proton pump inhibitor therapy if above causes excluded 2
• Consider adding prokinetic agent (metoclopramide) if initial therapy inadequate 2

Important: Chronic cough is frequently multifactorial—more than one cause may be present simultaneously, requiring sequential and additive therapy 2.

Safe Symptomatic Treatment Options

If symptomatic treatment is needed while investigating the cause:

Recommended:

• Guaifenesin (expectorant): Safe option that doesn't affect cardiovascular function 1
• Start with lowest effective dose to minimize potential cardiovascular effects 1

Avoid:

• Opioid-containing cough suppressants: Associated with higher rates of mechanical ventilation, ICU admission, and mortality in heart failure patients 1
• Sympathomimetic decongestants: Can worsen heart failure 1

Management Algorithm if Medication-Induced

If the cough is definitively attributed to sacubitril/valsartan and is troublesome enough to warrant intervention:

1. Do NOT discontinue the medication initially, as ACE inhibitor/ARB-induced cough rarely requires discontinuation 1
2. Optimize heart failure medications before making changes 1
3. If cough persists and significantly impacts quality of life: This presents a clinical dilemma, as sacubitril/valsartan provides mortality benefit in heart failure 7

Advanced Evaluation if Initial Approach Fails

If all common causes have been addressed without resolution 2:

• High-resolution CT scan: Evaluate for bronchiectasis or occult interstitial disease 2
• Bronchoscopy: Look for occult airway disease (endobronchial tumor, sarcoidosis, eosinophilic or lymphocytic bronchitis) 2
• 24-hour esophageal pH monitoring: If GERD suspected but empiric therapy failed 2

Critical Pitfalls to Avoid

• Never treat cough symptomatically without first ruling out pulmonary edema in heart failure patients 1
• Avoid concurrent use of non-dihydropyridine calcium channel blockers (diltiazem, verapamil) with respiratory medications in heart failure patients 1, 7
• Do not use NSAIDs or COX-2 inhibitors, as they can worsen heart failure and block diuretic effects 8
• Monitor for volume depletion when using Jardiance with diuretics, as the combination increases this risk 3