What is the comparative efficacy of sildenafil (phosphodiesterase type 5 inhibitor) and avanafil (phosphodiesterase type 5 inhibitor) for treating erectile dysfunction?

Comparative Efficacy of Sildenafil and Avanafil for Erectile Dysfunction

Avanafil demonstrates superior efficacy compared to sildenafil for erectile dysfunction treatment, with faster onset of action and greater improvements in erectile function scores after 12 weeks of treatment. 1

Mechanism and Indications

• Both sildenafil and avanafil are phosphodiesterase type 5 (PDE5) inhibitors specifically indicated for the treatment of erectile dysfunction in adult males 2, 3
• These medications work by selectively inhibiting PDE5, allowing corpus cavernosum smooth muscle to relax, which potentiates erections during sexual stimulation 4

Comparative Efficacy

Erectile Function Improvement

• High-quality evidence indicates that PDE5 inhibitors as a class significantly improve erections (73-88% improvement) compared with placebo (26-32%) 5
• In a recent randomized, double-blind, multicenter clinical trial directly comparing avanafil and sildenafil:
  • Avanafil showed non-inferiority to sildenafil at 4 weeks 1
  • Avanafil demonstrated superiority to sildenafil at both 8 and 12 weeks of treatment 1
  • The difference in International Index of Erectile Function - Erectile Function (IIEF-EF) score improvement progressively increased in favor of avanafil throughout the study period 1

Onset of Action

• Avanafil shows a significantly faster onset of action compared to sildenafil 1
• In direct comparison, 84.8% of patients using avanafil reported positive response to modified Sexual Encounter Profile 1 (measuring onset of action) compared to only 28.2% of sildenafil users (p<0.001) 1

Dose-Response Relationship

• For sildenafil, improvement in erectile function is related to higher dose (50 mg vs. 25 mg), though there appears to be less additional benefit when increasing from 50 mg to 100 mg 5
• In clinical practice, many patients are titrated from 50 mg to 100 mg sildenafil for improved efficacy 6
• Men treated with 100 mg sildenafil compared to 50 mg may achieve greater improvement in erectile function and completely hard erections within the first 2 weeks of treatment 7
• In the comparative trial between avanafil and sildenafil, 40.0% of patients in the avanafil group and 45.6% in the sildenafil group required dose escalation after 4 weeks 1

Safety and Tolerability

• Both avanafil and sildenafil are generally well-tolerated 1, 7
• The most common adverse effects for both medications include headache, flushing, rhinitis, and dyspepsia 5, 1
• Less common adverse effects include visual disturbances, myalgia, nausea, diarrhea, vomiting, dizziness, and chest pain 5
• The incidence of serious adverse events is less than 2% for PDE5 inhibitors, with no significant difference compared to placebo 5
• There is an absolute contraindication for concurrent use of PDE5 inhibitors with nitrates due to risk of severe hypotension 8
• In direct comparison, both avanafil and sildenafil showed similar safety profiles with headache being the most common adverse event in both groups 1

Clinical Considerations

• PDE5 inhibitors are effective for erectile dysfunction of various etiologies, including diabetes, depression, cardiovascular disease, prostate cancer, and other medical conditions 5
• Sildenafil has been shown to be more effective than non-PDE5 inhibitor treatments such as sublingual apomorphine, psychotherapy, and other medications 5
• Combination therapy with sildenafil plus other ED therapies (psychotherapy, atorvastatin, etc.) may provide greater improvements than sildenafil alone 5

Practical Recommendations

• Based on the most recent and highest quality comparative study, avanafil should be considered as a preferred option over sildenafil due to its superior efficacy at 8-12 weeks and significantly faster onset of action 1
• For patients who may need more rapid onset of action before sexual activity, avanafil offers a clear advantage 1
• For patients already established on sildenafil with good response, there may be no compelling reason to switch therapy 4
• Both medications should be avoided in patients taking nitrates due to risk of severe hypotension 8