Are phosphodiesterase-5 (PDE-5) inhibitors contraindicated in patients with atrial fibrillation or atrial flutter?

PDE-5 Inhibitors Are NOT Contraindicated in Atrial Fibrillation or Atrial Flutter

Phosphodiesterase-5 inhibitors (sildenafil, vardenafil, tadalafil) are safe to use in patients with atrial fibrillation or atrial flutter—there is no contraindication for these arrhythmias. The primary absolute contraindication for PDE-5 inhibitors is concurrent use with organic nitrates, not the presence of atrial arrhythmias 1, 2, 3, 4.

Key Safety Considerations

The Only Absolute Contraindication

• PDE-5 inhibitors are absolutely contraindicated only when patients are taking organic nitrates due to profound synergistic hypotension that can be life-threatening 1, 2, 3, 4
• Nitrates may be taken 24 hours after short-acting PDE-5 inhibitors (sildenafil, vardenafil) and 48 hours after long-acting formulations (tadalafil) 4

Cardiovascular Risk Assessment Required

• Before prescribing PDE-5 inhibitors to any patient with cardiovascular disease (including those with atrial fibrillation/flutter), estimate their cardiovascular risk during sexual activity 1
• Sexual activity is equivalent to walking 1 mile in 20 minutes or climbing 2 flights of stairs in 20 seconds 1
• Patients unable to perform these activities without symptoms should be referred to cardiology before ED treatment 1

Hemodynamic Effects in Atrial Fibrillation/Flutter Patients

Blood Pressure Effects Are Modest

• Sildenafil 100 mg decreases blood pressure by approximately -3.7/-3.6 mm Hg 2
• Vardenafil 20 mg decreases blood pressure by approximately -7.5/-8 mm Hg 2
• Tadalafil 20 mg decreases blood pressure by approximately -1.6/-0.8 mm Hg 2
• These mild vasodilatory effects do not pose specific risks related to atrial arrhythmias 2, 3

Drug Interactions to Monitor

• When combined with alpha-blockers (except tamsulosin), use the lowest doses of both medications due to risk of orthostatic hypotension 2, 3
• Additive blood pressure effects with most antihypertensives (beta-blockers, ACE inhibitors, ARBs, calcium channel blockers, diuretics) are small and clinically insignificant 3

Rate Control Medications and PDE-5 Inhibitors

No Contraindication with Standard AF/Flutter Medications

• Beta-blockers used for rate control in atrial fibrillation/flutter can be safely combined with PDE-5 inhibitors with only modest additive blood pressure effects 1, 2, 3
• Calcium channel blockers (diltiazem, verapamil) used for rate control have small additive hypotensive effects but are not contraindicated 1, 2, 3
• Digoxin has no significant interaction with PDE-5 inhibitors 1

Antiarrhythmic Drugs

• Amiodarone, when used for rhythm control, can be combined with PDE-5 inhibitors, though caution is needed due to multiple drug interactions amiodarone presents generally 1
• Class IC agents (flecainide, propafenone) and Class III agents (sotalol, dofetilide) have no specific contraindications with PDE-5 inhibitors 1

Special Populations

Pre-excitation Syndromes (WPW)

• The contraindications in WPW syndrome relate to AV nodal blocking agents (digoxin, verapamil, diltiazem, beta-blockers, adenosine), not PDE-5 inhibitors 1
• These AV nodal blockers can accelerate ventricular response during atrial fibrillation/flutter with pre-excitation by facilitating conduction down the accessory pathway 1
• PDE-5 inhibitors do not affect AV nodal conduction or accessory pathway conduction and are not contraindicated in WPW 1

Heart Failure with Atrial Fibrillation

• PDE-5 inhibitors are safe and effective in heart failure patients, including those with concurrent atrial fibrillation 5
• They may improve endothelial function, exercise tolerance, and quality of life in heart failure patients 5

Practical Prescribing Algorithm

1. Screen for nitrate use (absolute contraindication) 1, 4
2. Assess cardiovascular risk using the stair-climbing/walking test 1
3. Review concurrent medications for alpha-blockers (use lowest doses if combined) 2, 3
4. Start conservatively with the lowest effective dose and titrate as needed 1
5. Monitor for symptomatic hypotension, particularly in patients on multiple antihypertensives 2, 3

Common Pitfalls to Avoid

• Do not confuse atrial fibrillation/flutter with pre-excitation syndromes—the contraindications for AV nodal blockers in WPW do not apply to PDE-5 inhibitors 1
• Do not withhold PDE-5 inhibitors solely because a patient has atrial fibrillation/flutter—these arrhythmias are not contraindications 1, 2, 3
• Do not overlook nitrate use—this remains the only absolute contraindication and must be screened for in all patients 1, 4
• Do not assume all cardiovascular medications interact significantly—most rate control agents have only modest additive hypotensive effects 2, 3