Real-world data consistent with RCTs in highlighting the efficacy of drug-eluting technology

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real-world
Marianne Brodmann and Gunnar Tepe

During a recent satellite symposium, which took place at the 2022 Cardiovascular Interventional Radiological Society of Europe (CIRSE) annual meeting (10–14 September, Barcelona, Spain), experts emphasised the clinical value of drug-eluting technologies (DET) in peripheral arterial disease (PAD). The speakers, including Marianne Brodmann (Medical University of Graz, Graz, Austria) and Steven Kum (Mount Elizabeth Novena Hospital/Changi General Hospital, Singapore), gave an overview of trial results from Boston Scientific’s DET clinical programme and from independent investigators. Enrolment in these studies will exceed 10,000 patients in over 15 countries. 

Brodmann quoted the principal investigators of the EMINENT randomised controlled trial (RCT) who concluded that based on the EMINENT and IMPERIAL RCTs the Eluvia drug-eluting stent (DES) should be considered as the stent of choice for treating the superficial femoral artery (SFA) and/or proximal popliteal arteries of intermediate length. Kum also concluded that despite having more complex patients and longer lesions, the outcomes achieved in real-world registries are consistent with the data found in RCTs.

The power of RCTs

Opening the session, Brodmann delivered a presentation on RCTs for drug-eluting technology in PAD. The speaker first considered the power of randomised data, remarking that—after performance sensing through bench and pilot tests—“properly powered RCTs are essential to prove device performance against current standard of care with clinically meaningful primary endpoints”. After this, she noted, registry data should be used to confirm findings in real-world populations to “complement, not replace” RCTs.

The weight given to RCTs in clinical guidelines highlights their importance, Brodmann told the CIRSE audience, explaining that Level I evidence must be obtained from at least one RCT or from a meta-analysis of RCTs.

The first trial Brodmann mentioned was the COMPARE RCT, which included 414 patients. “This is the first head-to-head trial of drug-coated devices,” the presenter stated, detailing that the trial looked at the Ranger low-dose paclitaxel-coated device (Boston Scientific) versus the IN.PACT high-dose paclitaxel-coated device (Medtronic).

At 12 months, Brodmann reported, the primary endpoint for non-inferiority for a low-dose paclitaxel-coated DCB compared to a high-dose paclitaxel-coated DCB was met, as was the primary endpoint for non-inferiority regarding safety. The presenter added that, in the longer term (out to 790 days), the low-dose device performed as well as the high-dose device.

Brodmann then moved on to the RANGER II SFA Global study—an RCT of 396 patients that compared the Ranger DCB to plain balloon angioplasty. “We once again have good evidence at 12 months with regard to the primary patency*,” the presenter revealed, noting that this was superior to plain balloon angioplasty at a rate of 89.8% compared to 74.0% and was statistically significant.

The primary safety endpoint was also met, Brodmann continued, stating that clinically driven target lesion revascularisation (TLR) in the Ranger DCB arm was only 5.5% compared to 16.5% in the plain balloon arm. At two years, Brodmann communicated that primary patency was also statistically significant in favour of the Ranger DCB, as was freedom from TLR. “Longer-term data are very much needed for DCBs,” she stressed.

Moving on to the next study, Brodmann informed delegates that the head-to-head IMPERIAL study of 465 RCT patients directly compared the Eluvia (Boston Scientific) and the Zilver PTX (Cook Medical) devices. At this point, Brodmann explained that the drug release from the Eluvia system is sustained much longer than the Zilver PTX. At one year, the presenter reported that primary patency for the Eluvia was 86.8% compared to 77.5% for the Zilver PTX—a “statistically significant difference”. There were also statistically fewer TLRs in the Eluvia arm compared to the Zilver PTX arm, Brodmann added.

Finally, Brodmann spoke on the randomised EMINENT trial, which compared the Eluvia stent to a bare nitinol stent in 775patients. “This is the largest randomised trial of DESs for SFA and proximal popliteal arteries reporting patency to date,” she remarked, going on to describe it as a “landmark trial” in this field. Statistically significantly greater primary patency was achieved in patients treated with the Eluvia compared to the bare metal stent, Brodmann noted, adding that there was also sustained primary clinical improvement.

Brodmann quoted the EMINENT RCT principal investigators’ conclusion that, “Based on the EMINENT and IMPERIAL RCTs, the Eluvia DES should be considered as the stent of choice for treating the SFA and/or proximal popliteal arteries of intermediate length.”

Real-world data

Following Brodmann’s presentation, Kum reiterated that the results of these randomised studies “cannot be fully extrapolated to daily practice” and must be complemented by real-world registries.

Kum made this comment during a presentation on real-world patients and drug-eluting technologies, citing the single-centre Münster registry (62 patients), single-centre Auckland registry (51 patients), single-centre DESAFINADO registry (67 patients) and the multicentre Japanese CAPSICUM registry (1,097 patients) as key examples of real-world data on the Eluvia DES.

The 12-month primary patency results in the four registries were 87%, 94%, 84% and 87% and 12-month freedom from TLR rates were 87%, 94%, 92% and 93.8%, respectively, Kum reported. He also concluded that despite having more complex patients and longer lesions, the outcomes achieved in real-world registries are consistent with the data found in randomised clinical trials.

In the final presentation of the symposium, Brodmann gave a progress update on the ELEGANCE registry, underlining first the key issue at the centre of this study: “Despite the high prevalence of PAD in women and under-represented minorities, clinical trials rarely include significant sized cohorts.”

“Given the heterogeneity of PAD patient representation, there is a need to better understand how PAD treatments affect such cohorts,” she added.

The ELEGANCE registry aims to include up to 5,000 patients at up to 100 global study centres, with enrolment targets of 40% women and 40% under-represented minorities. The patients will be treated with drug-eluting devices from Boston Scientific.

Brodmann reported that 634 patients had been enrolled as of September 2022, and that the trial is ahead of its inclusion targets at 42% women and 42% under-represented minorities.

“To make a difference, we need to be different,” Brodmann commented. “ELEGANCE is an excellent example of partnership between industry and physicians as we aim to be a diverse, multi-dimensional source of real-world data in PAD treatment outcomes. By emphasising diversity and inclusion in clinical trial leadership and patient enrolment, we can expand patient representation in PAD trials and improve clinical decision-making and outcomes.”

Closing the session, moderator Gunnar Tepe (Klinikum Rosenheim, Rosenheim, Germany) considered what is next for the space, acknowledging that there are some open questions that need addressing. He referred, for example, to the use of drug-eluting devices in long lesions or in the case of restenosis after DCB. Overall, however, he summarised that, based on the data presented during the symposia, “paclitaxel-coated devices are safe in the SFA”.

PI-1580801-AA

*Kaplan Meier primary patency


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