Disclosures: Mykoniatis and Sullivan report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
February 19, 2021
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Combination therapy more effective than monotherapy for erectile dysfunction

Disclosures: Mykoniatis and Sullivan report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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A combined therapy of phosphodiesterase type 5 — or PDE5 — inhibitors and other treatments was associated with improved outcomes in patients with erectile dysfunction, according to research published in JAMA Network Open.

“This systematic review and meta-analysis demonstrated that combination therapy of [two] first-line [erectile dysfunction] treatments or other treatment modalities plus PDE5 inhibitors was associated with improved erectile function without increased treatment-related [adverse events], compared with PDE5 inhibitor monotherapy,” Ioannis Mykoniatis, MD, MSc, of the department of urology at Aristotle University, Thessaloniki School of Health Sciences in Thessaloniki, Greece, and colleagues wrote. “Based on these findings, patients with resistant [erectile dysfunction] may experience good outcomes after receiving combination therapy without the risk of increased [adverse events].”

Doctor with male patient
A combined therapy of phosphodiesterase type 5 — or PDE5 — inhibitors and other treatments was associated with improved outcomes in patients with erectile dysfunction, according to research published in JAMA Network Open. Source: Adobe Stock.

Mykoniatis and colleagues conducted a systematic review and meta-analysis to evaluate whether erectile dysfunction combination therapies were linked to improved outcomes compared with erectile dysfunction monotherapy.

They searched MEDLINE, Cochrane Library and Scopus for randomized clinical trials and prospective interventional studies that included outcomes on combination therapy and recommended monotherapy in men with erectile dysfunction. The trials were published through October 10, 2020.

In the meta-analysis, the researchers assessed data from randomized clinical trials that compared outcomes in patients who received PDE5 inhibitors and another agent with those who only received PDE5 inhibitors. They also analyzed mean score changes in the International Index of Erectile Function (IIEF) from baseline, and the adverse events that occurred with different treatments in various subgroups of patients. The analysis included 44 studies involving 3,853 men with a mean age of 55.8 years.

Mykoniatis and colleagues determined that the use of combination therapy was associated with a mean IIEF score improvement of 1.76 (95% CI, 1.27-2.24; I2 = 77%; 95% PI, 0.56 to 4.08) compared with monotherapy.

The weighted mean difference (WMD) in IIEF score with the addition of another agent was 1.7 (95% CI, 0.79-2.61) for daily tadalafil, 3.5 (95% CI, 0.22-6.78) for low intensity shockwave therapy, 8.4 (95% CI,4.90-11.90) for vacuum erectile device, 3.46 (95% CI,2.16-4.76) for folic acid, 4.9 (95% CI, 2.82-6.98) for metformin hydrochloride and 2.07 (95% CI, 1.37-2.77) for angiotensin-converting enzyme inhibitors. However, they noted that each of these methods was based on just one study.

Mykoniatis and colleagues reported that combined therapy with PDE5 inhibitors and alpha blockers was not associated with an improved IIEF score.

When examining subgroups of patients with erectile dysfunction, the researchers determined that combination therapy was associated with improved IIEF scores in those with hypogonadism (WMD = 1.61; 95% CI, 0.99-2.23), those who did not respond to monotherapy (WMD = 4.38; 95% CI, 2.37-6.40) and in those with erectile dysfunction that was induced by prostatectomy (WMD = 5.47; 95%CI,3.11-7.83), compared with monotherapy alone.

They did not find a significant difference in treatment-related adverse events with combination therapy or monotherapy. However, they noted that there was significant heterogenicity in their findings.

Mykoniatis and colleagues concluded that, based on their findings, combination therapy is safe and improves outcomes, and therefore should be considered a first-line therapy for patients with refractory, complex or difficult-to-treat erectile dysfunction.

In an editorial published alongside the story, John F. Sullivan, MD, an assistant professor at the University of Massachusetts Medical School, and colleagues wrote that “combination therapy with dual short- and long-acting PDE5 inhibitors may have an additive effect and should be considered, even as a first-line initial strategy in cases of more advanced erectile dysfunction.”

“Because it appears that PDE5 inhibitors will remain the mainstay of erectile dysfunction management for the foreseeable future, an ideal complimentary therapeutic strategy is one that will act in synergy with these drugs,” they wrote.

References:

Mykoniatis I, et al. JAMA Netw Open. 2021;10.1001/jamanetworkopen.2020.36337.

Sullivan JF, et al. JAMA Netw Open. 2021;10.1001/jamanetworkopen.2020.37292.