ZEN Trial Shows DES to Be Safe and Feasible for ED, But Challenges Remain

December 25, 2012—Jason H. Rogers, MD, and coprincipal investigators Krishna Rocha-Singh, MD, and Irwin Goldstein, MD, published 6-month follow-up results from the first-in-man ZEN trial in the Journal of the American College of Cardiology (2012;60:2618–2627). The ZEN trial findings demonstrate that the use of drug-eluting stents to treat erectile dysfunction (ED) is both feasible and safe. However, Dr. Rogers explained that challenges remain and further study is needed before this treatment is more widely utilized. 

The ZEN trial involved the participation of physicians from a variety of specialty backgrounds and sought to evaluate the safety and feasibility of implanting a zotarolimus-eluting peripheral stent system (Medtronic, Inc., Minneapolis, MN) in focal atherosclerotic lesions of the internal pudendal arteries in men with ED and a suboptimal response to phosphodiesterase-5 (PDE-5) inhibitors.

As detailed in the Journal of the American College of Cardiology, patients with atherosclerotic ED and a suboptimal response to PDE-5 inhibitors were enrolled in this prospective, multicenter, single-arm safety and feasibility trial. A novel combination of clinical, duplex ultrasound, and invasive angiographic factors were used to determine eligibility for stent therapy. The primary safety endpoint was any major adverse event 30 days after the procedure. The primary feasibility endpoint was improvement in the International Indicator of Erectile Function (Erectile Dysfunction Domain) score ≥ 4 points in ≥ 50% of subjects at 3 months.

The published 6-month follow-up results included duplex ultrasound and angiographic imaging findings. Forty-five lesions were treated with stents in 30 patients, with a 100% procedural success rate and no major adverse events through follow-up. The primary feasibility endpoint was achieved in 59.3% of intention-to-treat subjects (95% confidence interval, 38.8%–77.6%) and 69.6% of per-protocol subjects (95% confidence interval, 47.1%–86.8%). Duplex ultrasound peak systolic velocity of the cavernosal arteries increased from baseline by 14.4 ± 10.7 cm/s at 30 days and 22.5 ± 23.7 cm/s at 6 months. Angiographic binary restenosis (≥ 50% lumen diameter stenosis) was reported in 11 of 32 lesions (34.4%).

From these data, the ZEN investigators concluded that among highly selected patients with ED and a limited response to pharmacologic therapy, stenting of the internal pudendal artery is feasible and is associated with clinically significant improvement in both subjective and objective measures of ED. 

“The ZEN trial represents an extraordinary collaboration between urologists, sexual medicine specialists, and vascular interventionalists," Dr. Rogers stated when discussing the trial with Endovascular Today. "Many patients with suboptimal responses to PDE-5 inhibitors are seeking alternate therapies for ED.

"While the placement of drug-eluting stents in men with focal atherosclerotic lesions was safe and feasible, the treatment effect was perhaps not as robust as originally hoped. In addition, many hundreds of men were screened to find a relative few who were eligible for stenting. Given these challenges, more research is needed before the [therapy studied in the] ZEN trial can be considered a mainline therapy for ED. Finding collaborative networks and funding will offer significant future challenges in attempts to advance this technique further.”