EuroPCR Features PAD Therapies in Early Development and Real-World Use

PARIS, France—A paclitaxel-eluting nitinol stent is being used to treat progressively more challenging femoropopliteal artery disease while maintaining safety and efficacy, reported a study of Japanese post-marketing data presented May 21, 2014, at EuroPCR. In the same Hot Line session, another presentation explored the use of ultrasound to facilitate paclitaxel delivery.

Zilver Put to the Test

Hiroyoshi Yokoi, MD, of Fukuoka Sanno Hospital (Fukuoka, Japan), and colleagues looked at 907 patients who received the polymer-free paclitaxel-eluting Zilver PTX stent (Cook Medical, Bloomington, IN) after its approval in Japan. At 12 months, clinical follow-up was available for 96% of patients and ultrasound assessment for 58%. Baseline characteristics and outcomes of this group were compared with those of 479 patients enrolled in the device’s pivotal RCT and 787 treated as part of a premarket single-arm study.

“The studies enrolled increasingly complex patients and lesions,” Dr. Yokoi noted.

Post-marketing patients were older, more likely diabetic, and had higher prevalence of renal disease. Notably, 82% of those with renal disease in the post-market era were in kidney failure and/or required dialysis. Lesions were longer than previously studied and treatment of in-stent restenosis more commonplace. A greater proportion of patients were Rutherford class 4-6 before their procedure (table 1).

Table 1. Baseline Characteristics Across Studies of Zilver PTX

 

RCT

 

Premarket

Japanese
Post-Marketing

Age, years

68 ± 10

67 ± 10

74 ± 9

Diabetes

50%

36%

59%

Renal Disease

10%

11%

44%

Lesion Length, cm

6.6 ± 3.9

10.0 ± 8.2

14.7 ± 9.7

In-Stent Restenosis

0

15%

19%

Rutherford Class 4-6

9%

11.2%

20%

 

Despite these shifts, results including freedom from TLR and from thrombosis/occlusion were maintained. Moreover, primary patency remained high (table 2).

Table 2. Outcomes Across Studies of Zilver PTX

 

RCT

 

Premarket

Japanese
Post-Marketing

Freedom from TLR
6 Months
12 Months

 
98.0%
91.6%

 
97.6%
89.5%

 
97.3%
91.4%

Freedom from Thrombosis/Occlusion
6 Months
12 Months

 
98.7%
98.1%


98.5%
97.3%

 
98.2%
96.8%

Primary Patency
6 Months
12 Months

 
95.6%
84.4%

 
96.3%
82.8%

 
96.7%
84.8%

 

“Japan post-marketing study results are positive and confirm the benefit of the Zilver PTX technology,” Dr. Yokoi concluded, noting that there were “no safety signals” such as increased thrombosis. The “consistency across studies” also is reassuring, he added.

Panelist Marc Bosiers, MD, of St. Blasius Hospital (Dendermonde, Belgium), asked about any antithrombotic medications given after the procedure. Dr. Yokoi replied that dual antiplatelet therapy with aspirin plus either clopidogrel or ticlopidine is preferred, and that aspirin plus cilostazol is insufficient.

Jack Tan, MD, of National Heart Centre Singapore (Singapore), another panelist, agreed that “the results of the real-world study are very good actually—surprisingly extremely good.” He asked whether there were any performance issues in the approximately 1 in 5 patients being treated for in-stent restenosis. That analysis is not yet available, Dr. Yokoi replied.

Ultrasound to Optimize Drug Delivery

In the second study, Roberto Gandini, MD, of the Medical University of Rome Tor Vergata (Rome, Italy), updated his presentation from last year’s EuroPCR about an ultrasound system developed by CardioProlific (Redwood City, CA) to enhance arterial delivery of paclitaxel, thereby reducing restenosis.

After conventional balloon angioplasty, ultrasound energy at 20 kHz frequency is directly applied via catheter to the vessel wall for 60 seconds, he explained. The catheter is removed, then a distal protection balloon is inflated to stop blood flow. A sheath then delivers a mixture of paclitaxel and contrast medium for 60 seconds, after which the mixture is aspirated.

The single-center study, intended primarily to evaluate safety, has now treated 21 patients with femoropopliteal artery disease. Lesion length measured 161.1 ± 48 mm, with 76% of patients having lesions with visible calcification and 70% with chronic total occlusion.

At 6 months, 1 patient developed restenosis. There was no death, MI, TLR, or amputation of the treated leg. By 12 months, there was 1 instance of TLR and 1 death (due to bowel ischemia).

“Our human feasibility studies indicate that ultrasound enhanced paclitaxel delivery inhibits smooth muscle proliferation after balloon angioplasty,” Dr. Gandini concluded. While the treatment needs further validation, it shows “great potential,” he said, and “fits well with the standard peripheral interventional techniques.”

Session co-chair Alberto Cremonesi, MD, of GVM Care and Research (Cotignola, Italy), commented, “This is really interesting, because you demonstrated that you can change the vessel and lesion compliance in some way [while following] the ‘leave nothing behind’ philosophy.”

However, Dr. Bosiers expressed “doubts about the paclitaxel effect,” citing the possibility that there could be ‘washout’ of the drug. “If you put a balloon in distally, even after predilatation of a lesion, you still have collaterals that are open,” he explained, adding that predilatation may in fact be more influential than paclitaxel in producing the benefit seen here.

According to Dr. Gandini, operators performing the ultrasound treatment use distal balloon protection and attempt to introduce the sheath as close as possible to the beginning of the occlusion in order to minimize loss of paclitaxel.

Follow-up through 2 years is important, stressed panel co-chair Antoine Sauguet, MD, of Clinique Pasteur (Paris France), reporting that other research has shown paclitaxel’s effect on patency to decrease after 1 year.

 


Sources:
1. Yokoi H. Post-market surveillance study of paclitaxel-eluting nitinol stents for treating femoropopliteal artery disease in Japan: 12-month results. Presented at: EuroPCR; May 21, 2014; Paris, France.

2. Gandini R. New therapy to treat femoropopliteal artery for critical limb ischaemia patients. Presented at: EuroPCR; May 21, 2014; Paris, France.

 

 

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Disclosures
  • Dr. Yokoi reports receiving honoraria from Cook.
  • Dr. Gandini reports no relevant conflicts of interest.

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