First-Time Data Revealed From Three-Year PROSPECT MONSTER DCB Registry

A large real-world registry comparing two widely used paclitaxel drug-coated balloons (DCBs) – Ranger (Boston Scientific) and IN.PACT Admiral (Medtronic) – in complex femoropopliteal disease will be explored this morning at LINC. Focusing on three-year outcomes in a medically challenging cohort, Tatsuya Nakama (Tokyo Bay Medical Center, Japan) will dissect how device design, paclitaxel dose and meticulous lesion preparation may shape long-term durability in everyday practice. 

In conversation with LINC Today before his presentation of the data, Dr Nakama began with a short introduction to the purpose of the study: “DCBs are an established treatment device for femoropopliteal artery disease, and paclitaxel is the most commonly used antiproliferative agent,” he said. “However, individual DCB platforms differ substantially in drug dose, coating technology, and excipient formulation, which may translate into differences in clinical outcomes. 

“Previously, the COMPARE randomized controlled trial demonstrated comparable efficacy and safety between the second-generation low-dose Ranger, and the first-generation high-dose IN.PACT Admiral.¹ Importantly, long-term follow-up data extending to five years have shown that Ranger maintains consistent efficacy and safety comparable to IN.PACT.”² 

However, Dr Nakama noted that, as a randomized trial, COMPARE enrolled a relatively selective population that may not fully reflect real-world clinical complexity. To address this gap, they designed the PROSPECT MONSTER study, a prospective real-world registry.³ Between April 2021 and March 2022, a total of 581 patients with femoropopliteal lesions were treated with either Ranger or IN.PACT were enrolled across seven cardiovascular centers in Japan. Using propensity score matching, they adjusted baseline characteristics to compare clinical outcomes between the two DCBs. 

“After matching, 358 patients in the Ranger group and 163 patients in the IN.PACT group were analyzed,” continued Dr Nakama. “The matched cohort represented a highly complex population, with a mean age of 74 years, approximately 33–35% on dialysis, 38% with chronic limb-threatening ischemia [CLTI], 31–35% involving the popliteal artery, a mean lesion length of approximately 18 cm, and severe calcification (PACSS grade 3–4) in 44–46% of lesions. 

At one-year follow-up, both DCBs demonstrated comparable clinical outcomes. In the present analysis, we report and compare the three-year clinical outcomes between the two groups.” At one year, low-dose Ranger and high-dose IN.PACT had similar primary patency in the matched cohort (~87% versus 81%) and similar clinically driven freedom from target lesion revascularization (TLR; ~93% versus 90%). At the three-year follow-up, the outcomes remained comparable between the two groups, stressed Dr Nakama. “Primary patency was 60.1% versus 48.4% (p=0.39), and freedom from clinically driven TLR (CD-TLR) was 71.0% versus 59.9% (p=0.76) for Ranger and IN.PACT, respectively.” 

Although these differences did not reach statistical significance, there was a numerically favorable trend toward higher patency and lower reintervention rates in the Ranger group, added Dr Nakama. “This tendency was already observed at one year, and appears to have gradually widened over time. However, given the inevitable decline in follow-up completeness at longer time points, it is difficult to draw definitive conclusions from these observations alone.” 

Commenting on the presence of any late catch-up between years one and three, Dr Nakama relayed that Kaplan-Meier curves for both primary patency and freedom from CD-TLR showed similar shapes between the two groups. As such, there was no clear signal of a disproportionate increase in restenosis detected on imaging, symptom recurrence, or clinically driven reintervention in either group between years one and three. “Consistent with prior reports of paclitaxel-coated DCBs, the treated segments did not appear to reach a stable plateau phase,” he clarified. 
“Instead, patency tended to decline linearly over time, while reintervention rates increased gradually, rather than exhibiting a distinct, clear ‘late catch-up’ phenomenon. It may be a natural course of peripheral artery disease itself.”

The matched population in PROSPECT MONSTER was medically complex, including substantial chronic kidney disease (CKD)/dialysis burden and CLTI. Dr Nakama underlined that a characteristic feature of Japanese clinical study is the high prevalence of CKD and dialysis, which are well-established risk factors for restenosis after DCB treatment. “Unfortunately, in the present analysis, we did not specifically assess whether these factors independently drove late restenosis across the entire cohort,” he said. 

“However, interaction analyses comparing Ranger and IN.PACT demonstrated no significant differences in restenosis risk according to dialysis status or clinical presentation. The hazard ratios were 0.87 (95% confidence interval [CI] 0.38–2.01, p = 0.92) for dialysis and 0.76 (95% CI 0.37–1.54, p = 0.75) for CLTI, indicating no significant device-specific interaction in these high-risk subgroups.” 

In interaction analyses for three-year restenosis risk, lesion length was the only subgroup showing a statistically significant interaction. In lesions ≥15 cm, Ranger was associated with a lower risk of restenosis (HR 0.49, 95% CI 0.27–0.91, p = 0.022). In contrast, no significant differences were observed for chronic total occlusions (HR 0.64, p = 0.46), severe calcification (PACSS grade 4; HR 1.40, p = 0.39), or popliteal artery involvement (HR 1.09, p = 0.41). Overall, from the perspective of three-year restenosis suppression, Ranger and IN.PACT demonstrated broadly comparable performance across patient and lesion subgroups.

In the study, intravascular ultrasound (IVUS) guidance was used in around 70% of cases, and lesion preparation was meticulous (with scoring/non-compliant balloons being common). To that end, the question was put to Dr Nakama as to how much of the durability signal is device-related versus technique-related, and whether he would expect similar results in systems with higher bailout stent rates. 

“Although detailed quantitative analyses are limited, the high use of IVUS guidance and meticulous lesion preparation – including frequent use of non-compliant and scoring balloons – may have contributed to optimal vessel preparation and a low bailout stent rate,” he said. “The observed three-year primary patency and freedom from CD-TLR rates are broadly consistent with previously reported (Ranger and IN.PACT) data, suggesting that long-term durability is largely driven by device performance rather than procedural technique alone. 

“Bailout stenting is primarily intended to prevent acute or subacute vessel closure due to dissection or recoil and therefore is unlikely to have a major impact on long-term outcomes. Accordingly, similar long-term results might be expected even in systems with higher bailout stent rates.” 

Of course, dosing remains a core discussion point. That is, as three-year outcomes stayed comparable, the biological and technical characteristics need consideration in the light of the paclitaxel dose (i.e. the impact of coating/excipient performance, drug transfer efficiency, and the quality of vessel preparation). 

“Because lesion preparation techniques and procedural quality were well balanced after matching, the observed equivalence is likely attributable to device (Ranger and IN.PACT) performance,” said Dr Nakama. “Regarding the Ranger device, despite a lower paclitaxel dose, efficient drug transfer and uptake into the vessel wall, together with reduced distal drug loss, may explain the comparable outcomes relative to high-dose IN.PACT DCB. 

“This contrasts with earlier-generation low-dose DCBs, which tended to show reduced efficacy. Given that paclitaxel is inherently cytotoxic, achieving comparable outcomes with lower drug exposure represents a meaningful technological advancement.” 

Dr Nakama offered his practical take-home moving forward, what the three-year study results mean in practice, and commented on the present and future data prospects. 

“The three-year follow-up of the PROSPECT MONSTER study demonstrates comparable clinical outcomes between Ranger and IN.PACT. These findings support the use of the low-dose DCB Ranger as a viable first-line option for complex femoropopliteal disease, alongside the extensively ‘high-evidenced’ IN.PACT DCB,” said Dr Nakama. 

“Longer-term follow-up to five years may further strengthen this evidence. While the lack of core laboratory adjudication and an independent clinical events committee represents a limitation, this does not undermine the value of the study as a real-world registry reflecting contemporary clinical practice.”

References

1. Steiner S, Schmidt A, Zeller T, Teet al. COMPARE: prospective, randomized, non-inferiority trial of high- versus. low-dose paclitaxel drug-coated balloons for femoropopliteal interventions. Eur Heart J. 2020;41:2541-2552. 

2. Steiner S, st al. COMPARE Clinical Trial 5-Year Results presented LINC 2024. 

3. Nakama T, Takahara M, Iwata Y et al; PROSPECT MONSTER Study Investigators. Low-Dose versus High-Dose Drug-Coated Balloon for Symptomatic Femoropopliteal Artery Disease: The PROSPECT MONSTER Study Outcomes. JACC Cardiovasc Interv. 2023;16:2655-2665.