Ylva Trolle Lagerros, MD, PhD, from the Karolinska Institutet in Stockholm, and colleagues used data from the Swedish Patient Register and the Prescribed Drug Register to examine the association between PDE5i treatment and cardiovascular outcomes in men with stable coronary artery disease treated with nitrate medication. Exposure was defined as 2 or more dispensed prescriptions of PDE5i.

The analysis included 55,777 men who were treated with nitrates and 5710 men treated with nitrates and a PDE5i. The researchers found that combined use of PDE5i treatment with nitrates was associated with increased mortality, cardiovascular mortality, noncardiovascular mortality, myocardial infarction, heart failure, cardiac revascularization, and major cardiovascular events (hazard ratios, 1.39, 1.34, 1.40, 1.72, 1.67, 1.95, and 1.70, respectively).

“Our goal is to underscore the need for careful patient-centered consideration before prescribing PDE5i medication to men receiving nitrate treatment,” senior author Daniel Peter Andersson, MD, PhD, from Stockholm University, said in a statement. “Furthermore, it justifies our efforts for continued research into the ambiguous effects of erectile dysfunction drugs on men with cardiovascular disease.”

One author disclosed ties to the pharmaceutical industry.

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Erectile Dysfunction Treatments

The Food and Drug Administration (FDA) has granted marketing authorization to Futura Medical for the over-the-counter (OTC) sale of MED3000, a topical treatment for erectile dysfunction (ED).

According to the Company, the gel formulation is applied to the penis just before sex and has an onset of action of 10 minutes. The drug-free product produces a rapid cooling effect followed by a warming effect. This stimulates the nerve endings on the head of the penis, which then leads to vasodilation and erection.

The topical therapy has been shown to be safe and effective in two phase 3 clinical trials. In the FM71 study (ClinicalTrials.gov Identifier: NCT04984993), MED3000 gel was compared with oral tadalafil 5mg in 96 male patients clinically diagnosed with a mix of mild, moderate, and severe ED.

Results showed that at 24 weeks, MED3000 gel demonstrated a statistically significant improvement in erectile function compared with baseline (as measured by the International Index of Erectile Function-Erectile Function score) and led to a clinically meaningful difference in improvement of erections (as defined in scientific papers by Rosen et al).

Onset of action was measured as a secondary endpoint. In the study, topical MED3000 demonstrated a 10-minute onset of action, which was faster than oral tadalafil 5mg. No serious adverse events were reported with the gel.

“The granting of marketing authorization by the US FDA as the first clinically proven, topical gel for the treatment of ED in the USA available without a doctor’s prescription is a huge milestone for Futura and highlights the incredible progress that the Company continues to make,” said James Barder, CEO of Futura Medical.  “FDA set a very high standard in evaluating the effectiveness and safety of De Novo Medical Devices. I am delighted that we met this standard with MED3000’s submission of 22 clinical, biocompatibility, human factors studies and performance bench tests which were rigorously reviewed and accepted by the FDA.”

The topical gel will be available without a prescription under the brand name Eroxon^®. The Company is currently in the process of securing a partner to launch the product in the US.

Matthew Adesuyan, from the UCL School of Pharmacy in London, and colleagues conducted a cohort study involving men aged 40 years and older with a new diagnosis of ED between 2000 and 2017 to examine the association between PDE5i initiation compared to nonuse and the risk for developing AD.

The study included 269,725 men; during a median follow-up of 5.1 years, 1119 were newly diagnosed with AD. The researchers found that the adjusted hazard ratio for AD was 0.82 for PDE5i initiators compared with nonuse. Individuals issued greater than 20 prescriptions had a reduced risk for AD (hazard ratios, 0.56 and 0.65 for 21 to 50 and >50 prescriptions, respectively). The primary findings were supported in a sensitivity analysis with a one-year lag period (hazard ratio, 0.82), but were not significant with inclusion of a three-year lag period.

“The findings of this large population-based study suggest that the use of PDE5i may be associated with a reduced risk of incident AD,” the authors write. “The greatest risk reduction was observed in those issued >20 prescriptions over a median follow-up of five years.”

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Benjamin Green, from the Male Fertility and Peyronie’s Clinic in Orem, Utah, and colleagues conducted a randomized, controlled trial of 40 men with Peyronie disease treated with collagenase C. histolyticum + RestoreX penile traction therapy + sildenafil or penile surgery + RestoreX penile traction therapy + sildenafil.

The researchers found that 50 and 21 percent of men in the collagenase C. histolyticum group and surgery group, respectively, reported being very satisfied following treatment, and more in the collagenase C. histolyticum group noted better subjective erectile function (100 versus 68 percent) and penile length (88 vs 16%). Lesser impacts on penile sensation were seen in the collagenase C. histolyticum group (75 vs 11% had no change), while International Index of Erectile Function-Erectile Function Domain changes were similar between the groups (+1.5 vs +2.5). Greater curve improvements (84 vs 54%) and higher rates of adverse events (50 versus 13 events) were seen in the surgery group, as was decreased penile length (−0.5 versus +1.0 cm).

“Rather than showing an advantage of one approach over the other, we hope our study will provide useful new data to inform discussions and decision-making, aimed at choosing the most appropriate treatment for each individual patient,” senior author Landon Trost, M.D., also from the Male Fertility and Peyronie’s Clinic, said in a statement.

The study was partially funded by Endo Pharmaceuticals. One author is an inventor of the RestoreX device, and receives royalties from the Mayo Clinic from the invention and owns stock in PathRight Medical (the manufacturer of the device).

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