Registry Supports Paclitaxel DCBs in CLI Patients to 2 Years

In all-comers with above- or below-the-knee lesions, mortality was 20% at 24 months and the major amputation rate was 6%.

Registry Supports Paclitaxel DCBs in CLI Patients to 2 Years

Registry data from Germany add evidence of the therapeutic value of a paclitaxel-based drug-coated balloon (DCB) for the treatment of critical limb ischemia (CLI) in highly comorbid patients, even in the setting of tissue loss, gangrene, and prior interventions.

“Our series showed that the Passeo-18 Lux DCB can be safely applied in real-world practice with significant and sustained functional improvement, pain relief, and low major amputation rates,” write Marianne Brodmann, MD (Medical University Graz, Austria), and colleagues in the paper published online September 16, 2020, ahead of print in JACC: Cardiovascular Interventions.

The Passeo-18 Lux (Biotronik) is not approved for use in the United States, but received CE Mark approval in Europe in 2014. BIOLUX P-III, the subject of the paper, is its postmarket, all-comers registry.

In an accompanying editorial, Beau M. Hawkins, MD, and Isaac C. Meier, MD (both from University of Oklahoma Health Sciences Center, Oklahoma City), say that the 6% major amputation rate at 24 months in this real-world population “is favorable and not suggestive of harm with a DCB technology.” However, this single-arm registry with fewer than 400 patients does not provide much insight into safety issues surrounding the paclitaxel-based Passeo-18 Lux DCB, they add.

Long-term mortality with paclitaxel-based devices for the treatment of PAD has been deeply scrutinized since the publication in late 2018 of a meta-analysis that showed an increased risk of mortality compared with placebo emerging beyond the first year after treatment with a DCB. A second meta-analysis by the same investigators showed numerically higher rates of major amputation and all-cause mortality in patients with below-the-knee PAD and CLI.

In the new paper, Brodmann and colleagues note that they are following US Food and Drug Administration recommendations to extend follow-up of the BIOLUX P-III registry patients out to 5 years.

Functional Improvements and Pain Relief

Of the 328 patients enrolled in the registry (422 lesions), 61% had diabetes, 44% had renal disease, and 44% had coronary disease. Nearly half (47.6%) had undergone prior peripheral interventions. More than half of patients had femoropopliteal lesions and 27% had below-the-knee lesions. Rutherford class ranged from 4 to 6, with moderate or heavy calcification present in 45% of all treated lesions and 61% of patients having tissue loss or gangrene.

Device success was 99.8%, technical success 99.1%, and procedural success 95.7%. About 12% of patients needed bailout stenting. At 24 months, the rate of major adverse events was 19.4%, clinically-driven TLR 12.1%, major target-limb amputation 6.1%, and mortality 20.1%.

Among patients who died during follow-up, 27% of deaths were cardiac, 5.5% were vascular, and 12.7% were due to cancer. Mortality was highest, at 30.4%, in Rutherford class 6 patients. At baseline, mean Rutherford class score was 4.9. By 24 months, 88.1% of patients saw improvement in their scores, which averaged 1.7. Ankle-brachial index, which was 0.64 ± 0.26 at baseline, rose to 0.83 ± 0.26 at 24 months (P = 0.0001). Significant reduction in pain also was seen, with 75% of patients having improved their Wong-Baker pain scale score compared with baseline (P < 0.0001).

While we’re waiting for a wound to heal, we also want them to be comfortable and functional. Pain, as everybody knows, is a driver of dysfunction. Eric Secemsky

In their editorial, Hawkins and Meier note several limitations, including limited imaging during follow-up, a higher percentage of femoropopliteal lesions than would be expected for a CLI cohort, and “modest” lesion lengths relative to daily practice. Still, they say the study helps fill a large gap in understanding how to improve the poor outcomes typical of CLI patients.

“Although technical evolution seems to have resulted in improved limb salvage rates, there remains a glaring need to prevent patients with PAD from progressing to chronic limb-threatening ischemia and to develop innovative therapies that mitigate cardiovascular risk once rest pain or tissue loss ensues,” they write.

Promising Data and Future Considerations

Eric Secemsky, MD (Beth Israel Deaconess Medical Center, Boston, MA), who wasn’t involved in the study, noted that in the 92 patients with below-the-knee lesions, patency at 24 months was 81.4% and clinically driven TLR was 11.6%. Despite concerns about competing mortality risks and attrition during follow-up, he called the performance of the device “impressive” for femoropopliteal artery lesions and “above performance goal expectations” for below-the-knee lesions in complex real-world patients.

Secemsky added that while it is important to keep in mind past failures such as IMPACT-DEEP, which showed elevated amputation rates in DCB-treated patients, “it’s nice to have some data that are promising for this population.”

He also commented on the pain relief, which was documented in two-thirds of patients in the BIOLUX P-III registry.

“We haven’t spent too much time on quality-of-life measures in the CLI population like we have in claudicants. We still are [focused on] wound healing and amputation rates, which are far and away the most important endpoints, but they don't always fully capture what a procedure does for a patient with CLI,” he observed. “Being pain free, both with ambulation and at rest, is incredibly important. Reporting that endpoint is meaningful, and supports the efficacy of this device, specifically in patients who don't have substantial tissue loss and are more in the pain category. While we’re waiting for a wound to heal, we also want them to be comfortable and functional. Pain, as everybody knows, is a driver of dysfunction.”

Brodmann and colleagues conclude that while randomized controlled trials powered for clinical endpoints are needed to confirm the clinical utility of DCBs for the CLI population, they require large numbers of patients and are slow to enroll. One ongoing RCT that is attempting to understand optimal management is BEST-CLI, which is looking at a 24-month endpoint for endovascular therapy versus open surgery and hopes to enrolled 2,100 patients.

“We are all anxiously waiting for that trial to complete enrollment and follow-up,” Secemsky added. In the meantime, he said the BIOLUX P-III registry results hint that there might be a broader role for DCBs in the CLI population.

“Drug-coated devices are able to be used in the endovascular arm of BEST-CLI, but we don't have below-the-knee DCBs [and] we don't have below-the-knee stents outside of off-label coronary stents,” he said. “When BEST-CLI completes, we're going to have important information no matter what. But, there are definitely going to be areas where we're going to be asking further questions about whether there are other opportunities for endovascular strategies based on things that have occurred while patients were being enrolled.”

Sources
Disclosures
  • This study was sponsored by Biotronik.
  • Brodmann reports honoraria from Abbott Vascular, Biotronik, Philips-Spectranetics, Medtronic, Daiichi Sankyo, Bayer Healthcare, and BD Bard; consulting for Boston Scientific, Medtronic, Spectranetics, Intact Vascular Shockwave, Bayer, Vesper Medical, and BD Bard; and has study support from 480 Biomedical, BD Bard, Biotronik, Medtronic, Philips, Shockwave, Med Alliance, Intact Vascular, and B. Braun.
  • Hawkins and Meier report no relevant conflicts of interest.
  • Secemsky reports speaking and consulting fees from Abbott, BD, Bayer, Cook, CSI, Janssen, Medtronic, and Philips; and research grants to his institution from AstraZeneca, BD, Boston Scientific, Cook, CSI, Medtronic, and Philips.

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