Is sildenafil safe for a male patient with heart failure who is taking sacubitril/valsartan (Entresto) and carvedilol, and also has diabetes?

Is Sildenafil Safe with Heart Failure?

Yes, sildenafil is generally safe in patients with stable heart failure, but it is absolutely contraindicated if the patient is taking nitrates, and should be used with caution in those with borderline blood pressure or recent decompensation. 1

Key Safety Considerations in Heart Failure Patients

Absolute Contraindications

• Concurrent nitrate use is an absolute contraindication - sildenafil potentiates major drops in blood pressure when combined with nitroglycerin or other nitric oxide donors 2, 3
• Nitrates should not be administered within 24 hours of sildenafil use 4
• This includes patients who may need nitrates for angina management 1

Interaction with Sacubitril/Valsartan (Entresto)

• No direct contraindication exists between sildenafil and sacubitril/valsartan - the concern is additive hypotensive effects, not a pharmacologic interaction 5, 6
• Sacubitril/valsartan may increase levels of certain statins through transporter inhibition (OATP1B1, OATP1B3, OAT1, OAT3), but this does not apply to sildenafil 5, 7
• Monitor blood pressure closely when combining these medications, particularly during initiation 5, 6

Interaction with Beta-Blockers (Carvedilol)

• Sildenafil should be used with caution when combined with mixed alpha/beta blockers like carvedilol - similar precautions as with pure alpha-blockers apply 3
• Patients should be stable on beta-blocker therapy before initiating sildenafil, and sildenafil should be started at the lowest dose (25 mg) 3
• The combination does not increase cardiovascular events but may cause symptomatic hypotension in some individuals 3

Cardiovascular Safety Profile in Heart Failure

Evidence from Clinical Trials

• Sildenafil causes modest, transient reductions in blood pressure (approximately -8/-5.5 mm Hg systolic/diastolic) that are similar in men with and without coronary artery disease 8, 3
• These blood pressure reductions do not stimulate reflex tachycardia and are generally well-tolerated 3
• Sildenafil does not affect cardiac contractility, does not increase ventricular arrhythmia risk, and does not negatively impact coronary oxygen consumption or exercise capacity 3

Heart Failure-Specific Considerations

• Patients with NYHA class III heart failure are considered indeterminate-risk and require cardiovascular assessment before sildenafil use 1
• The Princeton III Consensus recommends exercise testing or pharmacologic stress testing to ensure cardiovascular health is consistent with the physical demands of sexual activity 1
• In patients with heart failure with preserved ejection fraction (HFpEF), the RELAX trial showed sildenafil did not improve exercise capacity, though it was not associated with increased adverse events 1

Risk Stratification Approach

Low-Risk Patients (Can Use Sildenafil)

• Controlled hypertension 1
• Mild stable angina 1
• Successful coronary revascularization 1
• Uncomplicated past myocardial infarction (>8 weeks) 1

Indeterminate-Risk Patients (Require Further Assessment)

• NYHA class III heart failure - requires exercise testing or stress imaging before sildenafil use 1
• Moderate stable angina 1
• Recent MI (2-8 weeks) without intervention 1

High-Risk Patients (Defer Sexual Activity and Sildenafil)

• Unstable or refractory angina 1
• Uncontrolled hypertension 1
• Recent cardiovascular events 3
• Severe heart failure (NYHA class IV) 1

Practical Management in This Patient

For a male patient with heart failure taking sacubitril/valsartan and carvedilol with diabetes:

1. Verify no nitrate use - this is the critical safety check 2, 4

2. Assess heart failure stability - ensure NYHA class II or stable class III, not actively decompensated 1

3. Check baseline blood pressure - if systolic BP >100 mm Hg, sildenafil is generally safe; if 90-100 mm Hg, use lowest dose (25 mg) and monitor closely 5, 3

4. Start with lowest dose (25 mg) given the combination with carvedilol and sacubitril/valsartan, both of which can lower blood pressure 3

5. Monitor for symptomatic hypotension - dizziness, lightheadedness, or syncope warrant dose reduction or discontinuation 3

6. Consider exercise testing if NYHA class III or uncertain functional capacity - patient should achieve 4-6 metabolic equivalents without ischemia 1, 8

Common Pitfalls to Avoid

• Do not assume all heart failure patients cannot use sildenafil - the evidence shows it is generally safe in stable disease 9, 4
• Do not overlook hidden nitrate use - always ask specifically about nitroglycerin, isosorbide, or other nitrate preparations 2, 4
• Do not discontinue guideline-directed medical therapy (sacubitril/valsartan, carvedilol) to accommodate sildenafil - these medications reduce mortality and should be continued 1
• Do not ignore diabetes - erectile dysfunction is common in diabetic patients and shares cardiovascular risk factors, making cardiovascular assessment particularly important 1

Postmarketing Safety Data

• Over 6 million prescriptions written in the first 8 months after FDA approval, with 130 deaths reported - 77 had documented cardiovascular events, and 16 had taken or were administered nitrates 2
• Seven years of international postmarketing data from >13,000 patients show no increased risk of myocardial infarction or death when used according to labeling 3
• Observational studies of >28,000 men in the UK and 3,813 men in the EU confirm no special cardiovascular concerns when used appropriately 3