A small, first-in-man study suggests that in men with erectile dysfunction (ED) who do not respond to drugs like Viagra and Cialis, stenting pelvic arterial lesions can safely restore penile blood flow and may improve erections, according to a paper published online November 21, 2012, ahead of print in the Journal of the American College of Cardiology.

Early, 30-day data were presented in October 2011 at VIVA (Vascular InterVentional Advances), and the paper’s 6-month findings were recently updated with 12-month follow-up in October 2012 at the Transcatheter Cardiovascular Therapeutics 24th Annual Scientific Symposium.

For the multicenter ZEN trial, investigators led by Krishna Rocha-Singh, MD, of Prairie Vascular Institute at St. John’s Hospital (Springfield, IL), identified 30 men with ED and a suboptimal response to oral phosphodiesterase-5 (PDE5) inhibitors who met stringent clinical, angiographic, ultrasound inclusion criteria. Zotarolimus-eluting peripheral stents (Resolute; Medtronic; Minneapolis, MN) were implanted in diseased internal pudendal arteries, either unilaterally (n = 19) or bilaterally (n = 11).

All procedures were successful; no stent fractures were seen at follow-up.

Procedure Appears Safe

At 30 days, no patient experienced the primary safety endpoint of a major adverse event, defined as device- and/or procedure-related death; perineal gangrene or necrosis; or perineal, penile, or anal surgery (including TLR, TVR, or an arterial embolization procedure). Moreover, no subsequent safety events occurred over the following 11 months, Dr. Rocha-Singh reported at TCT 2012.

At 6 months, in an intention-to-treat analysis, more than half of the subjects (59.3%; 95% CI 38.8-77.6) met the primary feasibility endpoint of improvement in erectile function from baseline. In the per-protocol analysis (which excluded 5 patients with pelvic lesions not located in the internal pudendal arteries), 68.6% (95% CI 47.1-86.8) reported such improvement at 3 months, a proportion that rose to 84.2% at 12-month follow-up.

The mean angiographic percent stenosis decreased from 63.3% preprocedure to 23.3% postprocedure, then rose to 41.4% at 6 months. Binary restenosis was seen in 34.4% of lesions (95% CI 18.6-53.2). Meanwhile, as measured by Doppler ultrasound, peak systolic velocity in 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.

Better Patient Selection Sorely Needed

In an accompanying editorial, Mehdi H. Shishehbor, DO, MPH, and Femi Philip, MD, both of the Cleveland Clinic (Cleveland, OH), observe that only 23% of screened patients qualified for angiography, and of those only 7.8% qualified for intervention. This highlights “the need for appropriate patient selection,” they write. “Even more importantly, approximately 30% of subjects that met the peak systolic velocity and other inclusion criteria had minimal to normal angiographic appearance, emphasizing the need for more robust, noninvasive screening tools such as [CT or MR] imaging.”

Furthermore, they point out, penile arterial insufficiency is a diffuse process, and discrete lesions are seen in only one-third of patients. Therefore, stents alone may not be the best answer for all patients.

The editorial concludes that “given the prevalence of ED and its psychosocial impact, an appropriately powered randomized trial to evaluate [stenting] clearly is needed.” Meanwhile, Drs. Shishehbor and Philip add, “this field is in desperate need of a reproducible and easily performed noninvasive diagnostic tool that can identify [penile arterial insufficiency] and exclude venous leak accurately for proper patient selection and to avoid unnecessary procedures. Only then can this paradigm be revisited.”

Jumping the Gun?

“We learned from ZEN that placing stents in the pudendal arteries is feasible, but that erectile function is a complex disease and applying stent therapy just because we can may be jumping the gun,”  Howard C. Herrmann, MD, of the Penn Heart and Vascular Center (Philadelphia, PA), told TCTMD in a telephone interview.

Even among the highly selected patients in the trial, response to stenting was limited, Dr. Herrmann observed. “So we really need to take a step back now and do studies to better understand the prevalence of internal pudendal artery disease, the relationship of that disease to ED, the relation to other vascular territories, and the functional physiology of the anatomy that we observe,” he said. Importantly, the proportion of patients who have pudendal artery disease but not ED remains unknown, he added.

In the ongoing INDEED study, Dr. Herrmann and colleagues are investigating these questions using a combination of angiography and FFR. A similar exploratory study undertaken by the study authors, IMPASSE, was recently suspended when Medtronic withdrew its sponsorship, although according to Dr. Rocha-Singh, the investigators are applying for NIH funding.

Dr. Herrmann said he would support stenting for ED if it could be put on a solid, evidence-based footing. “I believe that there is a subset of patients who have internal pudendal disease who could potentially benefit from a mechanical therapy like stenting,” he said. “I’m just not sure that I know how frequent that is, what those stenoses look like, and what else has to be excluded to have some confidence that placing a stent will help.”

In a telephone interview with TCTMD, Dr. Rocha-Singh acknowledged that although the early data suggest that stenting may help patients with a vasculogenic cause for their ED, it is difficult to draw firm conclusions from such a small sample size. And establishing the vascular disease criterion is problematic in part because an appropriate cutpoint for reduced peak systolic velocity has not been validated, he noted.

Earlier Screening Advocated

On the other hand, many potential participants in ZEN were disqualified because of advanced disease in their pelvic arteries, Dr. Rocha-Singh observed. So one message to clinicians should be that before simply prescribing drugs like Viagra or Cialis to younger men with ED they should screen them for cardiovascular risk. The average age of men in ZEN was 60 years, and one-third had a history of MI or stroke, he noted. Not only would earlier screening enrich the pool of men who may benefit from stenting, it also could uncover peripheral artery disease, a “canary in the coal mine” for heart disease, he added.

This field is still in its early days, Dr. Rocha-Singh commented, but he believes the clear need for improved treatment for ED will spur further research. “Once the true prevalence of vasculogenic ED is pinned down, we’re going to be able to understand where to concentrate our efforts,” he said, adding that, “we still need to find the right patients and we need a lot of public and physician education.”

2. Shishehbor MH, Philip F. Endovascular treatment for erectile dysfunction: An old paradigm revisited. J Am Coll Cardiol. 2012;Epub ahead of print.

3. Rocha-Singh K. DES for ED: One-year clinical follow-up from the ZEN trial. Presented at: 24th Annual Transcatheter Cardiovascular Therapeutics Scientific Symposium; October 26, 2012; Miami, FL.

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