Editorial Comment

Hope Springs Eternal: TheUnfulfilled Promise ofFemoropopliteal Stenting

Krishna Rocha-Singh, MD

Prairie Heart InstituteSt. John’s HospitalSpringfield, Illinois

An ebb and flow of discovery and change has occurredin the endovascular treatment of atherosclerotic femoro-popliteal disease since the widespread use of balloonangioplasty nearly a quarter century ago. The promisingnew technologies of directional, rotational, and laseratherectomy were introduced a decade later and enjoyedbrief periods of fascination and popularity before fadingfrom our interventional consciousness. An early retro-spective case series of the balloon-expandable Palmazstent described encouraging results [1]; however, subse-quent randomized, controlled trials showed no benefitwhen compared to balloon angioplasty alone [2]. Yetanother wave of new technologies—brachytherapy,stent-grafts, and photodynamic angioplasty—has hit,again holding the promise of improved long-term bene-fits in this challenging vascular bed. However, until thefinal results of these trials are analyzed, balloon angio-plasty must still be considered the tarnished gold stan-dard of endovascular care in the femoropopliteal artery.So what new hope does the IntraCoil nitinol stent have tooffer? That is the question explored by Ansel et al. [3].

Two general types of endovascular stents are currentlyavailable, the classic balloon-expandable stent of whichthe Palmaz stent is the archetypal design, the self-ex-panding braided nickle-cobalt (e.g., Wallstent), and thenickel-titanium alloy nitinol stents (e.g., IntraCoil). Bal-loon-expandable steel stents provide a relatively inflexi-ble scaffolding to support the vessel lumen; however,they are at risk for compression after deployment, par-ticularly in the distal femoropopliteal segment [4]. Self-expanding braided stents, on the other hand, have thedisadvantage of exerting relatively minimal radialstrength within the vessel and may provide excessivemetal-to-artery coverage, thereby activating neoinitimalhyperplasia, leading to early restenosis. Nitinol stentsoffer a unique combination of thermodynamic memory

and, when appropriately sized, outward radial force toresist extrinsic compression.

It is dubious, however, whether the improved mechan-ical flexibility and radial hoop strength characteristics ofnitinol can overcome the hemodynamic and biologicalchallenges intrinsic to the femoropopliteal artery. Unlikethe iliac vessels, the femoropopliteal artery is a long,relatively low-pressure conduit with few side branches.Many severely debilitated patients present with eitherdiffuse disease or long occlusions with impaired tibialrunoff. Indeed, long-term patency after successful bal-loon angioplasty may depend less on specific lesioncharacteristics and more on the hemodynamics of in-flowand runoff and the number of patent tibial runoff vessels.Reporting on the predictors of long-term (60 month)arterial patency after angioplasty, Clark et al. [5] ob-served that a poor tibial runoff score (� 1 vessel) wasmore predictive of reduced long-term patency than lesiontype (stenosis vs. occlusion), lesion morphology, or pres-ence of a postangioplasty dissection flap. Lesion length,however, continued to be a strong predictor of long-termpatency: American Heart Association (AHA) category 1lesions (single stenosis �5 cm or occlusion �3 cm) hadan 87% 60-month patency rate compared to longer cat-egory 2 or 3 lesions (69% and 66%, respectively; P �0.006). In this regard, the mean 3.8 cm lesion lengthtreated by the IntraCoil investigators, demonstrating an82% 9-month patency rate, suggests that this stent maynot improve patency over balloon angioplasty alone inrelatively short diseased segments. A similar 85% 18-month patency rate using the same stent platform inlesions with a mean 4.5 cm lesion length was recentlyreported by Jahnke et al. [6]. We must therefore ask, canaddressing only the mechanics and neglecting the biol-ogy of restenosis improve stent patency?

Enter Cordis, a Johnson and Johnson Company. Join-ing the resources of its cardiovascular device and drugdivisions, Cordis scientists in 1996 began evaluatingnumerous drugs and polymer coatings in combinationwith new stent platforms. After discarding several can-didates, energies focused on sirolimus, a product ofStreptomyces hygroscopius, a molecule originally devel-oped by Wyeth-Ayerst as a potential antimicrobial agent.Exploiting the more potent antiproliferative properties of

DOI 10.1002/ccd.10287Published online in Wiley InterScience (www.interscience.wiley.com).

Catheterization and Cardiovascular Interventions 56:450–451 (2002)

© 2002 Wiley-Liss, Inc.

sirolimus, investigators quickly forged proprietary agree-ments with Wyeth-Ayerst and several polymer-coatingcompanies. The development of an appropriate drug-stent delivery platform was a daunting undertaking, re-quiring the development of new animal models of reste-nosis and novel polymers that could adhere to both steeland nitinol stents. Additionally, these drug-eluting stentshad to resist the degradation induced by heat sterilizationand prolonged shelf life. Finally, after years of collabo-rative efforts between drug development and stent designexperts, countless trial-and-error experiments, and mil-lions of investment dollars, the Cypher stent programwas born at Cordis in 2001 with the introduction of thesirolimus-eluting BX Velocity stent platform. Propelledby the nothing-less-than-spectacular 6-month results ofthe RAVEL trial, demonstrating a 0% angiographic re-stenosis rate in coronary patients [7], investigatorsmoved quickly into the periphery to address the chal-lenges of the femoropopliteal artery.

With much anticipation and expectation, the earlyresults of the sister peripheral trial, Sirolimus-CoatedCordis Smart Nitinol Self-Expanding Stent for the Treat-ment of Obstructive Superificial Femoral Artery DiseaseStudy (SIROCCO), were announced in January 2002 [8].This small pilot study (n � 36) randomized patients withsymptomatic femoropopliteal artery atherosclerosis(mean lesion length, 8.5 cm) to a noncoated Smart nitinolstent or to sirolimus-coated Smart stents. At 6-monthangiographic follow-up, restenosis occurred in 38% ofnoncoated stents and in none of sirolimus-coated stents.The initial excitement, however, was tempered whenclose core-laboratory angiographic inspection revealedeither partial or complete fractures of stent stines in sixpatients. While these fractures were of no immediateclinical consequence and occurred in both coated andnoncoated Smart stents, it raised questions of the possibleeffect of torsion and compression forces present in thefemoropopliteal artery and the potential need for stentdesign modifications. Nevertheless, despite the quiet andcautious excitement engendered by the early SIROCCOresults, it is difficult for many of us who have shared theangst and frustration of our patients with debilitatingperipheral vascular disease not to think ahead to thepotential implications of this new technology: an effec-tive therapy for diffuse femoropopliteal/infrapoplitealdisease, extended bypass graft and AV fistula patencyrates, the end of restenosis in diabetic patients–nothingshort of a major paradigm shift away from benign neglect

and deferred treatment toward aggressive and earlierintervention! From medical students to seasoned clini-cians, awareness, attitudes, and approaches toward pe-ripheral vascular disease patients will require readjust-ment.

The much anticipated pivotal SENTRY trial (Siroli-mus-Eluting Nitinol Stent in the Treatment of the Super-ficial Femoral Artery) is poised to launch in mid to late2002. Enrollment in this randomized trial of the sirolimusSmart stent versus balloon angioplasty in femoropopli-teal arteries will undoubtedly be brisk, reflecting theenthusiasm of its investigators in defining the boundariesof this new therapy. Of course, an element of skepticismis always appropriate: issues of total drug dose in patientsreceiving long segments of drug-eluting stents (safety),stent durability, and cost will require close study andscrutiny. Nevertheless, the quantum leap forward repre-sented by drug-eluting stents in interventional cardiovas-cular medicine may only be eclipsed by the advent ofstents themselves nearly a decade ago. For physiciansand patients alike, hope springs eternal.

REFERENCES

1. Henry M, Amor M, Ethevenot G, et al. Palmaz stent placement iniliac and femoropopliteal arteries: primary and secondary patencyin 310 patients with 2–4-year follow-up. Radiology 1995;197:167–174.

2. Grimm J, Muller-Hulsbeck S, Jahnke T, et al. Randomized study tocompare PTA alone versus PTA with Palmaz stent placement forfemoropopliteal lesions. J Vasc Intervent Radiol 2001;12:935–941.

3. Ansel G, Botti C, George B, et al. Clinical results for the trainingphase roll-in patients in the IntraCoil femoropopliteal stent trial.Cathet Cardiovasc Intervent 2002;56:443–449.

4. Rosenfield K, Schainfield R, Pieczek A, et al. Restenosis of endo-vascular stents from stent compression. J Am Coll Cardiol 1997;29:328–338.

5. Clark T, Groffsky J, Soulen M. Predictors of long-term patencyafter femoropopliteal angioplasty: results from the STAR registry.J Vasc Intervent Radiol 2001;12:923–933.

6. Jahnke T, Voshage G, Muller-Hulsbecks, et al. Endovascular place-ment of self-expanding nitinol coil stents for the treatment offemoropopliteal obstructive disease. J Vasc Intervent Radiol 2002;13:257–266.

7. Morice M, Serruys P, Sousa J, et al. A randomised double-blindstudy with the sirolimus coated BX Velocity balloon expandablestent in the treatment of patients with de novo native coronaryartery lesions: late breaking clinical trials. Atlanta, GA: AmericanCollege of Cardiology. March 2002.

8. Duda S. The SIROCCO study: a clinical investigation of thesirolimus coated cordis Smart stent for the treatment of obstructivesuperficial femoral artery disease. Miami, FL: International Sym-posium on Endovascular Therapy (ISET). January 2002.

Hope Springs Eternal 451