The MISAGO Registry: A Rapid-Exchange Superficial Femoral Artery Stent for a Rapidly Expanding Field

Abstract

In the past decade, a number of nitinol self-expanding stents have been developed for the treatment of femoropopliteal occlusive disease. Early generation stents were hampered by high rates of fracture and restenosis, but recent stent designs have shown decreased fracture rates and improved midterm patency.^1–3 Superficial femoral artery (SFA) stenting, with either a nitinol self-expanding stent or a covered stent such as the Viabahn, is becoming increasingly common, even for complex lesions and long occlusions.^4–6 A paclitaxel-eluting stent is currently under review for Food and Drug Administration approval and has shown promise in a randomized trial and multicenter registry.⁷ Despite the wide availability of a number of stent types, most published studies of SFA stenting have included fewer than 200 patients and are limited to patients with stable claudication and moderate length lesions. Additional data on larger groups of patients will help guide decisions on more complex anatomical subtypes and direct real-world treatment of patients with claudication or critical limb ischemia (CLI).

In this issue of the JEVT, Schulte et al.⁸ present outcomes of the MISAGO-2 registry, which studied the use of the Misago stent in patients with claudication or CLI and femoropopliteal occlusive disease. The Misago is a second-generation nitinol-based self-expanding stent with a rapid exchange (Rx) delivery system. The Rx design allows faster stent delivery over shorter length wires, as well as greater ease of use by a single operator. Other potential advantages of this stent platform include a zigzag cell design that provides added flexibility and the potential for reduced stent fracture. Early experience with this stent in the MISAGO-1 registry demonstrated excellent midterm results and safety in a small group of 55 patients.⁹

In the currently reported MISAGO-2 registry, 744 patients with symptomatic femoropopliteal disease (Rutherford category 2–6) underwent balloon angioplasty and stenting with the Misago stent. The major anatomical inclusion criterion included a total lesion length <180 mm, allowing treatment with up to 2 stents. The primary endpoint was target lesion revascularization (TLR) at 12 months. The treated lesions had a mean length of 63.9±37.4 mm, 37.6% were chronic total occlusions, and >80% were isolated to the SFA. Accordingly, >85% of the treated lesions were characterized as TASC II (TransAtlantic Inter-Society Consensus) category A or B. At 12 months, only 10.1% of patients required TLR. Among the patients who had follow-up radiography, 3.1% had evidence of stent fracture; none of these fractures resulted in a need for revascularization.

The results of the MISAGO-2 registry show compelling efficacy and safety for this stent in the study population. Strengths of the study include its large population and real-world application to patients with both stable claudication and CLI. Notably, 20% of the study population included patients with Rutherford category 4–6 disease, whereas many prior SFA stent studies have excluded patients with CLI. Based on the reported results, the Misago stent had excellent midterm clinical patency in this diverse group of patients. The multicenter nature of the study also increases its generalizability, as the reported results represent the practices of many centers.

While the study has a number of strengths, it should also be interpreted in the context of its design and endpoints. Although this was a multicenter trial, the study coordinators did not use a central core angiographic or ultrasound laboratory, nor were dedicated flexed knee films mandated during follow-up. It is therefore possible that the rates of stent fracture are understated. Additionally, the patency endpoint did not include mandated duplex ultrasound. The excellent primary patency rates that the authors report (87.6%) should therefore be interpreted with caution. Despite inclusion of lesions up to 180 mm in length in this registry, the lesions actually treated were relatively short (mean length of 63.9 mm); even the lesions >70 mm only averaged 111.7±32.5 mm. In comparison, recent studies with other stent platforms have reported initial results in longer SFA lesions.^5,10

How do the results of the Misago registry compare to previously reported randomized trials and registries of SFA stenting? Despite improvements in outcomes of SFA stenting, lesion length remains a primary determinant of restenosis. The mean length of 63.9 mm in the MISAGO-2 registry is consistent with medium-length lesions treated in recent clinical trials, including the RESILIENT (RandomizEd Study Comparing the Self-ExpandIng Lifestent vs. Angioplasty Alone In LEsions INvolving The SFA and/or Proximal Popliteal Artery) study (mean lesion length 71 mm) and the randomized arm of the Zilver PTX study (mean lesion length 66 mm).^7,11 In the RESILIENT study, the 12-month freedom from TLR was 87.3%. Similarly, the Zilver PTX trial reported 90.5% freedom from TLR at 12 months. The results of the MIASGO-2 registry therefore appear comparable with other self-expanding stents in lesions of similar length. In the absence of independent core lab ultrasound review, however, restenosis rates with the Misago stent remain uncertain.

Overall, the results of the MISAGO-2 registry provide evidence of clinical efficacy for this stent platform in the treatment of moderate length SFA disease. Ease of delivery with a rapid exchange system may also make the Misago stent compelling for everyday use. This stent is currently undergoing further evaluation in the US and Japan as part of the OSPREY study, which recently completed enrollment. In the US arm of this study, 200 patients were enrolled at 31 centers in a single-arm nonrandomized design. The primary endpoints were primary patency by ultrasound or angiography and freedom from major adverse events. More data regarding ultrasound outcomes will therefore be available soon.

With the recent profusion of SFA stent registries and randomized trials, the inevitable issue of comparative effectiveness will arise. Are all second-generation self-expanding stents the same? In the literature on coronary artery stenting, most stent platforms are thought to be largely similar, although small differences in outcomes have emerged in large studies involving thousands of patients. Stent outcomes in the SFA will more likely depend on subtleties of stent design, given the variable compression and torsion forces to which these stents are exposed. It is therefore possible that different nitinol-based platforms will have differential restenosis rates during long-term follow-up. Further complicating this issue is the availability of alternative technologies, including drug-eluting stents, covered stents, drug-eluting balloons, and atherectomy devices. Now that multiple self-expanding stents have demonstrated improved efficacy, the time has come for comparative trials with clinically meaningful outcomes.

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