Results of the first study of a first-generation drug-coated balloon (DCB) with a biolimus coating for the treatment of in-stent restonsis—REFORM—have shown that the device failed to meet non-inferiority compared to a paclitaxel-coated device.
Robert Byrne (RSCI University of Health Sciences, Dublin, Ireland) reported the findings of the study at EuroPCR 2023 (16–19 May, Paris, France).
DCBs are seen as an appealing treatment option for in-stent restenosis as once the drug has been delivered using the device, no permanent metallic structure is left behind in the vessel, unlike with a stent.
“Patients who have undergone PCI with a drug-eluting stent still fall foul to in-stent restenosis,” Byrne commented in his presentation, noting that this outcome occurs in roughly 3–5% of patients. “Guideline recommended treatments include repeat stenting with drug-eluting stents and angioplasty with a drug-coated balloon,” Byrne noted.
To date, paclitaxel has been the coating of choice for the majority of DCBs due to its lipophilic properties that assist its transfer and retention at the vessel wall. Limus-based drugs such as sirolimus have supplanted paclitaxel in drug-eluting stents, where they have shown superior safety and efficacy, as well as having a wider therapeutic range than paclitaxel, but, a crucial difference in DCB-usage has been that the drug is absorbed more slowly into the vessel wall.
The prospective, randomised, non-inferiority trial pitted the Biolimus A9-coated balloon (Biosensors) against the SeQuent Please (B Braun) paclitaxel DCB, over a primary endpoint of percentage in-segment diameter stenosis at six months.
The REFORM study screened a total of 351 patients for inclusion, Byrne reported at EuroPCR, with 135 randomised to receive the Biolimus-coated device, and 66 randomised to receive the SeQuent Please, paclitaxel-coated device.
Detailing the results of the study, Byrne reported that percentage in-segment diameter stenosis at six months was 41.8% with the Biolimus-coated balloon versus 31.2% for the paclitaxel-coated balloon, meaning that the investigational device did not meet its criteria for non-inferiority.
Commenting on further endpoints of note, Byrne stated that late lumen loss recorded with the investigational device averaged 0.50mm, compared to 0.20mm with the comparator—the lowest of any prior study in in-stent restenosis using the SeQuent Please device—while binary restenosis stood at 32.2% and 11.3% in each cohort, respectively.
Offering up explanation for the findings, which he claimed were “not in line with expectations”, Byrne said: “One might be a difference in the rate of negative late lumen loss or positive vessel remodelling which was observed more frequently with the paclitaxel-coated device, as compared with the Biolimus-coated device.
“In addition, one might comment that the performance of the control device, the Sequent please was excellent in this study and out performed that in other trials with a late lumen loss of 0.20.”
Furthermore, Byrne noted that in the first-generation Biolimus-coated balloon, the crystalline coating had a crystal size of around 10 microns, whereas a second-generation iteration has been developed with a smaller crystal size which he said can result in higher tissue levels in the same preclinical models and has received clinical trial approval in China.
“Initial data has become available from the BIO-RISE trial in patients with small vessels showing that it out performs balloon angioplasty, and a trial in in-stent restenosis is ongoing and is expected to report this year,” Byrne commented.