ZEN: DES Works for Select ED Patients, But Finding Them Proves Difficult

Reed Miller

October 25, 2012

MIAMI — One-year results from the first-in-man ZEN trial show that Medtronic's zotarolimus-eluting peripheral stent is a durable therapy for erectile dysfunction (ED) in select patients [1]. However, the difficulty of identifying the patients who will benefit from the therapy has deterred the company from further development of the device.

Here at TCT 2012, ZEN investigator Dr Krishna Rocha-Singh (Prairie Vascular Institute, Springfield, IL) and Dr Jason Rogers (University of California, Davis Medical Center, Sacramento) explained that the study struggled to enroll patients, enrolling only 30 of the 383 patients originally screened for inclusion. The ZEN inclusion criteria define a group of patients with discrete lesions of the internal pudendal arteries that would be amenable to stenting, so many patients had to be excluded because the disease in their pelvic vasculature was too diffuse to be treated with a stent, Rocha-Singh explained.

"For us to have a screened failure rate of 92% means that we're missing the appropriate population," Rocha-Singh told heartwire . The average age of patients considered for the ZEN trial was 60, but research has shown that ED begins to manifest in the late 40s or 50s. PDE-5 inhibitor drugs for erectile dysfunction often stop working after three to five years of chronic use, so by the time patients come to their doctor complaining that the PDE-5s are no longer working, they probably have already begun to develop vascular disease and are at risk for cardiovascular events, according to Rocha-Singh.

ZEN "defined the importance of patient selection and evaluating these patients decades earlier," Rocha-Singh said. By the time cardiologists see these patients, they probably already have coronary disease, so it is therefore up to the general internists to identify patients in whom the beginning of erectile dysfunction is a harbinger of progressive vascular or coronary disease, he said.

"We need to educate general internists who put these patients on these medications to follow up with them to make appropriate referrals to urologists and specifically ED urologists, because not all urologists are ED urologists," he said. Internists may also consider referring patients to a vascular lab that can do a duplex Doppler ultrasound of the penis. Unfortunately, not many of these labs have staff that knows how to conduct that exam, he said.

Medtronic Gives up on ED Stents for Now

Joseph McGrath, Medtronic's director of corporate communications, cardiac and vascular group, told heartwire , "Due to the diagnostic screening challenges encountered during the enrollment phase of the ZEN trial, we decided after a great deal of consideration and consultation to suspend our clinical program for vasculogenic erectile dysfunction. Appropriate patient selection proved more difficult than anticipated."

As a result of this decision, Medtronic suspended the Incidence of Male Pudendal Artery Stenosis in Suboptimal Erections Study (IMPASSE), an angiography study intended to define normal pelvic anatomy and correlate the pathologies of pelvic vasculature to erectile dysfunction. The study was planned for 350 subjects at 15 sites. The patients who were enrolled will be followed for five years, and their results will eventually be publicized.

Early Benefits Last at Least a Year

All of the patients enrolled in ZEN had erectile dysfunction that was not responding to PDE-5 inhibitor drugs. All of the patients had International Index of Erectile Function (IIEF-6) scores >6 and <21, peak systolic velocity (PSV) in their penile cavernosal arteries <30 cm/s, and obstructive stenosis of the internal pudendal arteries (between 70% and 100% for unilateral stenosis or between 50% and 100% in each vessel for bilateral stenosis).

The new data Rocha-Singh announced at TCT showed that 84.2% of the patients (16/19) who reached the one-year follow-up improved at least 4 points on the IIEF-6 score. As reported by heartwire , at three months, over two-thirds of patients (15/22) showed at least 4 points of improvement on the IIEF-6 score. Five patients have been lost to follow-up, and Singh says he has asked Medtronic to help the investigators track them down.

The one-year ZEN results also showed that the safety of this peripheral drug-eluting stent is excellent, with no deaths; perineal gangrene or necrosis; no perineal, penile, or anal surgeries; no target lesion or target vessel revascularizations; and no arterial embolization procedures.

Rocha-Singh also pointed out that the average PSV of the patients' penile cavernosal arteries was 32.2 cm/s, compared with an original baseline average velocity of 16.4 cm/s.

"The patients who did respond--and these are people who failed Viagra, Cialis, and so forth--continued to maintain a very strong and robust clinical effect, and that was correlated with maintenance in their peak systolic velocities, [so] there was no placebo effect. A placebo effect does not last a year," Rocha-Singh said.