Which conditions respond best to 5-phosphodiesterase (5 PDE) inhibitors for erectile dysfunction (ED)?

Conditions That Respond Best to PDE5 Inhibitors for Erectile Dysfunction

PDE5 inhibitors should be offered as first-line therapy for erectile dysfunction in most patients, with the general ED population showing the best response, while men with diabetes and post-prostatectomy patients respond less robustly. 1

Patient Populations and Response Rates

• The general ED population shows the highest response rates to PDE5 inhibitors, with similar efficacy across sildenafil, tadalafil, vardenafil, and avanafil 1
• Men with mild cardiovascular disease who are classified as "low risk" (asymptomatic coronary artery disease with fewer than three risk factors, controlled hypertension, mild stable angina, successful coronary revascularization, uncomplicated past MI, mild valvular disease, or CHF NYHA class I) respond well to PDE5 inhibitors 1
• Patients with specific conditions show variable response:
  • Men with diabetes have more severe ED at baseline and respond less robustly to PDE5 inhibitors 1
  • Post-prostatectomy patients have more severe ED at baseline and show reduced response to PDE5 inhibitors compared to the general population 1
  • Men with spinal cord injury may benefit from PDE5 inhibitors but require lower initial doses due to potential delayed metabolism 2

Contraindications and Risk Stratification

• PDE5 inhibitors are contraindicated in patients taking nitrates due to potentially dangerous hypotension 1
• High-risk cardiac patients should not receive treatment for sexual dysfunction until their cardiac condition has stabilized, including those with:
  • Unstable or refractory angina
  • Uncontrolled hypertension
  • Left ventricular dysfunction/CHF (NYHA class II or greater)
  • MI or CVA within previous 2 weeks
  • High-risk arrhythmias
  • Hypertrophic obstructive cardiomyopathies
  • Moderate-to-severe valvular disease 1
• Patients with intermediate cardiovascular risk should undergo further evaluation by a cardiologist before receiving PDE5 inhibitors 1

Comparative Effectiveness Among PDE5 Inhibitors

• All FDA-approved PDE5 inhibitors (sildenafil, tadalafil, vardenafil, and avanafil) have similar efficacy in the general ED population 1
• In trade-off analyses:
  • Sildenafil 50mg shows the greatest efficacy but also has the highest rate of overall adverse events 3
  • Tadalafil 10mg demonstrates intermediate efficacy with the lowest overall rate of adverse events 3
  • Vardenafil 10mg and avanafil 100mg have similar adverse event profiles to sildenafil 50mg but lower global efficacy 3

Special Considerations for Specific Populations

• For men with spinal cord injury:

  • Lower initial doses are recommended due to potential delayed metabolism 2
  • Multiple medication trials may be required to establish efficacy 2
  • Combining PDE5 inhibitors with testosterone therapy may be more effective in men with concurrent testosterone deficiency 2

• For men with predominantly psychogenic ED:

  • PDE5 inhibitors are still effective as first-line therapy 1
  • Referral to a psychotherapist may be beneficial as either an alternative or adjunct to medical treatment 1

Optimizing Treatment Success

• Proper patient education is essential as incorrect use accounts for many treatment failures 2
• Dose titration should be performed to provide optimal efficacy 1
• Periodic follow-up is necessary to assess efficacy, side effects, and any significant changes in health status or medications 1
• For patients who fail initial PDE5 inhibitor therapy, evaluation should determine whether the trial was adequate before proceeding to alternative therapies 1

Common Side Effects

• Most frequently reported adverse events include dyspepsia, headache, flushing, back pain, nasal congestion, myalgia, visual disturbance, and dizziness 1
• Side effect profiles are similar across medications with some exceptions:
  • Dyspepsia: lowest rates with avanafil 1
  • Flushing: lowest rates with tadalafil 1
  • Myalgia: lowest rates with vardenafil and avanafil 1