the stent decade: 1987 to 1997

Progress in Cardiology

A decade of device development has followed Sig-wart’s seminal description of intracoronary stentimplantation.1 In these 10 years, interventional cardiol-ogists have contributed to the evolution of more than20 stent designs in pursuit of the broad indications ofantirestenosis, dissection stabilization, aneurysm exclu-sion, and antiembolization.

In January 1997, a select panel of experts met at Stan-ford University to review their collective experiencewith coronary and peripheral vascular stenting whilecharting investigative pathways for future stent develop-ment. The international faculty included cardiologists,radiologists, pathologists, and regulatory personnelalong with representatives from the device industry.

This report summarizes the summit proceedings. Itcondenses what emerged as a “near consensus” regard-ing our current understanding of stent technology andclinical application while identifying the controversial

issues awaiting resolution by basic investigation, reg-istries, and randomized clinical trials.

Basic pathology: Stent-tissueinteraction in human vasculature

A limited experience with the pathologic examina-tion of stented human vessels suggests that the anti-restenosis effect of intracoronary stenting is neitherpredictable nor complete.

At the Armed Forces Institute of Pathology, Farb etal.2 analyzed postmortem specimens from 42 stentedcoronary segments in 27 patients. This study pro-vides further insight into the nature and time courseof the vascular response to stenting. Figs. 1 through4 demonstrate the range of pathologic specimensencountered.

From these autopsy specimens of stented arteries it isclear that disruption and injury of plaque and vesselwall lead to substantial stent-tissue interaction. One ofthe major issues of future stent design, from a biologicperspective, may be the differential response fromstents that penetrate plaque compared with those thatmerely compress the plaque mass.

Although remodeling and shrinkage appear to play afundamental role in restenosis after conventional bal-loon angioplasty (percutaneous transluminal coronaryangioplasty [PTCA]), intimal hyperplasia is the predom-inant mechanism of intrastent restenosis; this neoin-tima, with its proliferating smooth muscle cells and a

The stent decade: 1987 to 1997Stephen N. Oesterle, MD, Robert Whitbourn, MD, Peter J. Fitzgerald, MD, PhD, Alan C. Yeung, MD, Simon H. Stertzer,MD, Michael D. Dake, MD, Paul G. Yock, MD, and Renu Virmani, MD, for the Stanford Stent Summit facultyStanford, Calif., and Washington, D.C.

In January 1997, experts from the United States, Europe, and Japan gathered at Stanford University to review their collectiveexperience with intracoronary and noncoronary stenting and to identify and prioritize issues requiring further clinical investi-gation. This report summarizes the discussions that took place during this stent summit. Knowledge of stent-tissue interactionfrom animal and human pathologic specimens was reviewed in the context of evolving stent designs. The relative merits ofcoil and slotted tubular stent designs were discussed. Stent deployment routines, including self-expansion, balloon expansion,and high-pressure delivery were debated. The potential for covered stents and coated stents was explored. Problems sur-rounding the routine deployment of stents were identified: small vessel disease, long lesions, bifurcation stenoses, vein graftdisease, ostial disease, left main stenoses, and intrastent restenosis. The value of intravascular ultrasound, as an adjunct tostenting, was explored and debated. An algorithm for “provisional stenting” based on ultrasound criteria was developed.Noncoronary stenting of the aorta, iliacs, and carotids were discussed. Clinical applications that may lead to randomizedclinical trials were identified. (Am Heart J 1998;136:578-99.)

From the Division of Cardiovascular Medicine and the Division of Interventional Radi-ology, Stanford University School of Medicine; and the Armed Forces Institute ofPathology.Supported in part by unrestricted grants from Boston Scientific/SciMed Life Systems,Cook Cardiology, Cordis/Johnson & Johnson Interventional Systems, Arterial Vascu-lar Engineering, Guidant, Medtronic, Progressive Angioplasty Systems, and SchneiderInternational.Submitted Oct. 15, 1997; accepted Feb. 13, 1998.Reprint requests: Stephen N. Oesterle, MD, Division of Cardiovascular Medicine,Stanford University Medical Center, H2103, 300 Pasteur Dr., Stanford, CA 94305.0002-8703/98/$5.00 + 0 4/1/89572

American Heart JournalVolume 136, Number 4, Part 1 Oesterle et al 579

proteoglycan matrix, is not appreciably different fromthat seen after PTCA (see Fig. 4).

The basic principle that extensive medial injuryleads to more inflammation is common to all coronaryinterventions. Rupture of a necrotic core, with expo-sure of the plaque contents, appears to be a potentstimulus for inflammation and profuse proliferation ofsmooth muscle cells.

Stent deployment within saphenous vein grafts isregularly associated with extrusion of a gruel-likematerial through the strut lattice, frequently incitingthrombosis and a marked inflammatory response. Theresultant proliferation of a robust neointima mayexplain the high rates of restenosis in stented humanvein grafts. This phenomenon has stimulated thedevelopment of “covered stents” as a way to mitigatethe intense thrombotic and inflammatory responseafter stent implantation in degenerated grafts.

Table I summarizes our understanding of factors thataccelerate neointimal proliferation in stented humancoronary arteries.

The need to mitigate the tissue injury associatedwith stent deployment represents a significant chal-lenge for new stent design. The majority of stents areballoon expandable and typically deployed at rela-tively high pressure (8 to 18 atm). Depending on thestent structure, implantation can lead to significantinjury to the internal elastic lamina, media, and, attimes, adventitia. Virmani et al. and others have raisedthe possibility that self-expanding stents, with theirgradual development of radial force, may be prefer-able to balloon-expandable stents that rely on high-pressure balloon expansion.3,4 Slow progressiveexpansion of a stent may allow or even facilitatefavorable vascular remodeling that is frequently seenafter stent implantation. Alternatively, the persistentradial force of a self-expanding stent may be a contin-uous source of injury, stimulating an even more exu-berant healing response.

Animal models as surrogates for stent assessmentThe common domestic pig serves as an excellent

model for intimal hyperplasia after coronary inter-vention. The porcine model is especially suitable forstudying human coronary interventions because ofcomparable coronary anatomy; the size of the coro-nary vessels are similar, and selective intubation ofporcine coronary ostia can be accomplished easilywith conventional, “off-the-shelf” guiding catheters.

A major difference with human histology arises in

the adventitia: rich in elastic fibers for the pig but pre-dominantly collagen in human beings (see Figs. 1, 4,and 7). In contrast to the pig, the external elastic lam-ina in human beings is a single, thin membrane.

There is a striking similarity in the neointimal hyperpla-sia seen in pigs, dogs, and human beings (Figs. 4 through7). The number of cells, their composition, and accompa-nying proteoglycan matrices are essentially the same.

We have learned from the pig model that there is adirect relation between the extent of injury and theproliferative response.5 Fig. 6 is a cross section of astented coronary artery with variable degrees ofinjury. There appears to be more neointima at sites ofgreater penetration and injury. This provides a patho-physiologic explanation for the observation that thelate loss with stenting is actually greater than withother coronary interventions. The larger acute gainassociated with stenting allows for this enhanced lateloss to occur without significant clinical consequence;consequently, coronary stenting has led to a demon-strated reduction in clinical restenosis.6,7

Schwartz et al.5 at the Mayo Clinic have determinedthat different species have different responses to com-parable amounts of arterial injury. There is minimalneointimal thickening after injury in the rat model.Likewise, in the dog model, there is trivial intimal pro-liferation, even after substantial trauma to the mediaand adventitia (Fig. 7). Figs. 5 and 7 depict the dra-matic difference in intimal response after comparableinjury in porcine and canine models.

The proliferative response to arterial injury in the pigis exaggerated and frequently greater than that seen inhuman beings. The early development of intracoronarystents might have been unwittingly aborted had stentpioneers selected pigs instead of dogs as the surrogatefor stent evaluation. The predictably unfavorable resultsof implantation of prototype self-expanding stents in apig could have discouraged investigators from furtherpursuit of stent technology.

Excessive thrombosisInflammationDeep injury to the arterial wall from balloon angioplasty and

adjunctive therapyPoor apposition of stent to arterial wallUnderlying proliferative lesionLarge necrotic core commonly seen in saphenous vein graft athero-

sclerosis and in thrombosis caused by plaque rupture of nativecoronary arteries

Table I. Causes of increased neointimal formation in stentedcoronary arteries

American Heart JournalOctober 1998Oesterle et al580

Despite the aggressive tissue response com-monly seen in the pig, this human surrogate ispreferred by the United States Food and DrugAdministration because of its apparent predictabil-ity. Within 6 months, sufficient “late” data areavailable to facilitate decisions regarding progres-sion to human trials.

Nuances in stent design: Arevariations really important?Balloon-expandable versus self-expanding designs

Interventionists in the United States have been con-strained to the use of balloon-expandable stentdesigns (Johnson & Johnson Palmaz-Schatz stent, theCook FlexStent (Cook, Inc) and GR II, and more

Figure 1

Three different histologic compositions of atherosclerotic coronary plaques from patients dying from severe coronary artery disease.A, Plaque rupture with overlying thrombus (T) and rupture of thin fibrous cap (arrowhead) with underlying necrotic core (NC) show-ing hemorrhage; lesion usually seen in patients with unstable angina or acute myocardial infarction. B, Atherosclerotic plaque rich infibrous collagenous tissue and absence of necrotic core with mild calcification (arrows) of plaque; this is eccentric plaque with normalmedia (M) and overlying minimal fibrointimal tissue; lesion is usually seen in patients with stable angina. C, Plaque showing markedcalcification (black areas) of plaque; lesion is usually seen in stable angina.

of the vessel wall) may adversely affect vessel remodel-ing and restenosis. Both types of stents typically requiresecondary balloon expansion after initial deployment.

Foreshortening of self-expanding stents is commonlyencountered upon withdrawal of their constrainingsheaths, so that precise positioning can be a formida-ble challenge. Positioning of balloon-expandable stentsis more predictable. The prototypical self-expandingstent first used by Sigwart (Wallstent, Schneider) hasrecently been modified as the Magic stent, and alongwith the other new generation self-expanding stentssuch as the SciMed Radius stent, experience signifi-cantly less foreshortening on deployment.


recently, the ACS Multilink (Guidant) and MedtronicWiktor stent). Clinical experience in Europe (and at asmall number of investigative sites in the United States)with self-expanding stents has identified a fundamentaldifference between balloon expansion and self-expan-sion in regard to sizing of the stent. With balloon-expandable stents, the operator generally sizes the stentto the minimum reference diameter and subsequentlymolds the delivered stent to conform to the vessel con-tour. With self-expanding stents, the stent is typicallysized to the maximum reference diameter. In bothcases, incorrect sizing or deployment of stents (forexample, with protrusion of struts through to adventitia

Figure 2

A, Histologic section of left anterior descending coronary artery taken from patient who died 1 day after rotational atherectomy andstenting. Note ruptured media (between arrows) but intact external elastic membrane. Center of lumen shows folds from cutting arti-fact and postmortem clot (PC). B, Higher magnification of A, close to top arrow showing infiltration of adventitia by neutrophils andmedia (M) is largely devoid of nuclei, representing cell necrosis. C, High-power view of stented left anterior descending artery from apatient who had Palmaz-Schatz stent placed 5 months before sudden death. Note chronic inflammatory infiltrate, giant cells (arrow-heads), and neovascularization (N) with overlying neointima (NI). Media is seen underneath the stent strut.

It may be that slow expansion, associated with self-expanding stents, will lead to larger lumens, over time,with attenuated injury. This phenomenon has beenobserved in an animal model in the absence ofplaque.8 Fig. 8 demonstrates the time-dependentgrowth in lumen area seen over a 28-day period in aporcine coronary artery stented with a self-expandingdevice. It is not known whether these same findingswill prevail in human atherosclerotic coronary seg-ments. It remains to be determined whether the slowgrowth of self-expanding stents will yield greater lategains than those associated with the immediate largelumens achieved with balloon-expandable stents.


The self-expanding SciMed Radius stent is currentlybeing compared with the Cordis/Johnson & JohnsonPalmaz-Schatz stent in a randomized clinical trial. Fol-low-up angiography from this study may validate orrepudiate the hypothesis that less late loss will attendgradual stent expansion.

Slotted tubular versus coil stent designsThe Johnson & Johnson Palmaz-Schatz stent is the

prototype for slotted tubular stent designs. A series ofmodified stents appears to be derived from modifica-tions of this design including the NIR stent (BostonScientific), the BeStent (Medtronic), ACS Multi-Link(Guidant), and the Sito stent (JoMed). The prototypicalcoil stent was designed by Gianturco and subse-quently developed by Cook, Inc., as the Gianturco-Roubin FlexStent. Derivative coil designs include theWiktor stent (Medtronic), the GR II stent (Cook), theXT stent (Bard), and the Strecker stent (Cordis). TheAVE Microstent has features of both coil and slottedtubular designs.

The slotted tubular design stents generally providegreater surface coverage of the stented lesion. Coilstents once had the general advantage of enhancedflexibility; recent-generation, slotted tubular stentshave narrowed this gap. Coil designs have also beenparticularly attractive choices for stenting long, softlesions associated with significant dissection after bal-loon angioplasty. These stents continue to providegreater access to covered side branches. In the caseof complex bifurcation lesions, coil stent designs areoften favored because of their flexibility and greaterpotential for side-branch access and dilatation. Coilstents can be deployed easily in both limbs of a bifur-cation with proximal overlap as illustrated in Fig. 9.

Until recently, no clinical trial had demonstrated thesuperiority of either design for simple lesions <15 mmin length, though interventionists have generally pre-ferred slotted tubular designs over coil stents. Recentresults of a randomized clinical trial comparing CookGR II and Johnson & Johnson Palmaz-Schatz stentsshowed an increased residual diameter stenosis for thecoil stents, which related to higher restenosis rates.9

This is despite stents with a coil design having thepossibility for less late loss because of the putativepotential for less injury upon deployment.

The advent of the NIR, BeStent, ACS Multilink, andAVE Micro stents, with their enhanced trackability, haslargely supplanted the use of the Palmaz-Schatz stent inEurope. Their novel designs have overcome the inherent

Figure 3

A, Stented coronary artery from patient who died on sameday of stent implantation. Note thrombotic (TH) occlusion ofstented artery and dissection (D). Thin fibrous cap is rupturedin between arrows in B, and stent struts (arrowheads) arelocated adjacent to area of ruptured fibrous cap. Necroticcore (NC) is in direct contact with luminal blood.

inflexibility of the Palmaz-Schatz stent and are deliveredwith the ease that has been associated with coil designs.

Despite the several theoretical advantages of coilstents, the summit faculty believed that problems oftissue prolapse and weak radial strength are inherentdesign flaws that probably will lead to the eventualextinction of the coil design.

Long stentsInterventionists working in the United States have had

a remarkably limited selection of stents: a 15 mm articu-


lated Palmaz-Schatz stent, 12 mm and 20 mm CookFlexStents, and 20 and 40 mm Cook GR II stents. Morerecently, the 25 mm Multilink (Guidant), the 24 mmCrown (Cordis, Johnson & Johnson), and a 32 mm AVEmicro were approved by the US Food and Drug Admin-istration. There is a clear need for longer stents to coverextensive dissections and diffuse coronary artery disease.It is common to use 3 or more sequential stents in a sin-gle arterial segment; with some spiral dissections morethan 6 stents have been serially deployed. The use ofmultiple stents is expensive, time consuming, and fre-

Figure 4

Balloon angioplasty in this artery was performed 12 months before death of patient. Note ruptured media (between arrows) andmarked intimal proliferation [light area (arrowheads)] surrounding lumen (L). B, Coronary artery section in which Cook Gianturco-Rubin Stent was placed 10 months before death of patient. Note neointima that is circumferential (arrowheads) and site of strut wire(arrow) is seen within media. C, Higher magnification of area of stent strut (arrow) within media and superimposed neointima that isrich in smooth muscle cells and proteoglycan matrix. Neointima resulting from balloon angioplasty and stenting is similar.

quently confounded by problems of precise placementwithout an excessive gap or overlap. The availability oflong (>30 mm) stents in a noncoil design is mandatoryfor immediate treatment of life-threatening spiral dissec-tions; widely available in Europe and Asia, such stentsare not approved for use in the United States.


Reliable data in regard to the restenosis rate withlonger stents are not available; it is generally thought tobe substantially higher than that seen with stents <20mm. It is unclear whether higher restenosis rates arerelated to greater metal—tissue interaction or simply tothe presence of more extensive disease. Little is known

Figure 5

Sections of coronary arteries from dog (A) and pig (B) in which MULTI-LINK balloon-expandable stents have beenplaced for 1 month. Although there is less neointima in dog than in pig artery, character of neointima is similar inboth and resembles that seen in stented human arteries. Media is compressed underneath struts (black rectangles).

Figure 6

Pig coronary artery sections from left circumflex (A) and left anterior descending (B) coronary artery 14 days after balloon-expand-able tantalum stent placement. Note concentric lumens with greater medial wall injury, best appreciated in B in lower right quadrant(arrowheads). A does not show severe injury and has less neointimal formation.

about the ultralate implications of deploying long stentsegments in coronary arteries. The long-term influencesof powerful contraction and torsion on stent migrationand metal fatigue have not been specifically addressed.

Premounted versus unmounted stentsA dichotomy in deployment strategies has clearly

emerged from operators in the United States andtheir overseas colleagues. Interventionists in theUnited States are supplied with premounted stents.Unmounted coronary stents cannot be distributed inthe United States. Unmounted stents are commonlyused outside the United States because of the pre-vailing preference of physicians to mount stents onspecific balloon catheters of their choice. In Europe,

lower-profile, semicompliant, rapid exchange bal-loon catheters are now favored for mounting “bare”stents.

Mounted stents (as provided in the United Statesby Cordis/Johnson & Johnson, Guidant, Arterial Vas-cular Engineering, and Cook, Inc.) have an advan-tage in that they are more difficult to dislodge or slipoff of the delivery balloon. Premounted stents havethe highly desirable advantage of rapid “off-the-shelf” deployment occasionally required for treatingabrupt closure in the laboratory. The major disad-vantage of the current generation of premountedstents is that most are delivered on larger-profile bal-loons incapable of withstanding high-pressure infla-tion. Their use generally requires the use of a sec-


Figure 7

Sections of dog (A and B) and pig (C and D) coronary arteries that had prior balloon injury. Note neointimal formationin both animals. Area of neointima is outlined by arrows where media (M) is disrupted. Neointima in both animals isproportional to severity of injury. The nature of neointima (NI) is similar in the 2 animals, consisting of smooth musclecells in proteoglycan matrix. Adventitia is markedly different in the 2 animals. In the dog, external elastic lamina is sin-gle layered whereas in the pig it is multilayered (black region). (Courtesy of Dr. Richard Stack, Duke University.)

diffuse atheromatous debris regularly encountered inaged or degenerated vein grafts. Coronary artery andvein graft ruptures have been stabilized by the emer-gency deployment of a covered stent.12 The potentialof “stent grafts” to exclude aneurysms has been dra-matically demonstrated in larger, noncoronary ves-sels13 (see Fig. 10).

The development of synthetic materials that canfacilitate low-profile delivery of covered stents whileminimizing thrombosis and late inflammation remainsa major challenge of stent engineering.

Coated stentsAlthough heparin-coated stents have been used in a

primary antirestenosis strategy (BENESTENT II14) andin the context of primary angioplasty for acutemyocardial infarction (PAMI III pilot15), investigatorscontinue to doubt the importance of this coating. It isgenerally believed that thromboresistant coatings are


ond “postdeployment” balloon for high-pressureapposition and complete expansion of the stent. Thepresence of a protective sheath also introducesadded profile and a nontapered leading edge.

Most unmounted (“bare”) stents are hand crimpedonto a balloon by the operator; there is considerableoperator variability in the technique and success of thisprocedure. Touching the stent may introduce debris,such as talc or cotton fibers, onto the metal.

The faculty agreed that premounted stents probablywould dominate future designs provided that they aremounted on lower-profile balloons with appropriatecompliance and burst characteristics.

Covered stentsThe use of covered stents remains investigational;

most have been prototypes, covered with either non-biodegradable polymers or autologous vein.10,11

Although covered stents have the potential to mitigatelate loss by excluding migration and proliferationthrough the exposed stent cells, their larger collapsedprofiles have precluded routine deployment.

The potential for clinical use of covered stents issubstantial. They have particular appeal for covering

Figure 8

Effect of self-expanding stent on lumen area, evaluated over a28-day period in porcine model. Three self-expanding nitinolstents of different expansile strengths (low, <0.05; moderate,0.06 to 0.09; high 0.10 to 0.13 lb/mm) were implanted andevaluated by intravascular ultrasound immediately after place-ment and at 28 days. Although no relation existed betweenstent strength and vessel injury (as assessed by histomorphome-try at baseline), there is significant increase in luminal area seenwith increasing expansile strength. Reprinted with permissionfrom the American College of Cardiology (Journal of the Ameri-can College of Cardiology, 1997, Vol 29, Suppl A, page 313A).

Figure 9

Stenting bifurcation stenosis. A, Second flexible coil stent canbe delivered easily through coils of first stent with proximaloverlap of coil segments (B).

figure not available


unnecessary when proper stent deployment tech-niques are coupled with effective antiplatelet medica-tion (aspirin and ticlopidine). The BENESTENT II pilotstudy demonstrated lower restenosis rates withheparin-coated stents; however, most investigatorsbelieve that this reduction in intrastent proliferationwas related to improved deployment technique andnot a direct consequence of heparin coating.

The potential for application of antiproliferativecoatings remains provocative and largely unexplored.

Bifurcated stentsBifurcation disease is an anatomic subset of coro-

nary stenoses that confounds operators both becauseof the mechanical challenge and the high incidenceof restenosis. Existent stent technology has not pro-vided a satisfactory solution for stenting bifurcations.

The deployment of “kissing” coil stents is an estab-

lished approach to bifurcation disease. Fig. 11 depictsa fundamental problem with this technique: poor cov-erage of the apices of the lesion.

Operators have used a “half stent” techniquewhereby one half of a disarticulated Palmaz-Schatzstent is deployed in the side branch, with a full Pal-maz-Schatz stent placed in the main vessel (Fig. 12). Ifthe side branch does not have a nearly orthogonal ori-gin, the technique will leave a proximal section ofplaque in the side branch uncovered.

Although “kissing” Palmaz stents are routinelydeployed at the aorta-iliac bifurcation, the creation ofa “new carina” in the smaller bifurcated coronary cir-culation has little precedent.

Most of the summit faculty harbored basic reluc-tance to stent both branches of bifurcation stenoses,favoring debulking with either directional or high-speed rotational atherectomy as a primary approach.

Thoracic aortic aneurysm excluded by covered stent graft. Prosthesis has a Z-stent endoskeleton covered with a modified Dacron tubegraft (Courtesy of Michael Dake, MD).

Figure 10

Bifurcated stent strategies have been reserved forcases associated with important dissections or signifi-cant residual stenoses.

Clinical issues associated with stentingDebulking

Considerable controversy surrounds the clinical con-sequences of prestent debulking. Moussa et al.16

reported the results of a consecutive series of coronarystenting of complex and calcified lesions after pretreat-ment with rotational atherectomy and reported a highrate of procedural success and a low angiographicrestenosis rate compared with those usually obtainedin these lesion subsets. The faculty agreed that ostialdisease, complex bifurcation stenoses, and diffuse cal-cified disease appear to have favorable responses toprestent debulking. However, no controlled clinicalstudies have validated the routine use of debulkingstrategies before stent implantation.

Prestent plaque debulking has the potential to mod-ulate the compliance of a vessel, thus (1) securing asuccessful acute result by facilitating the delivery ofthe stent, (2) allowing full stent expansion at lowerpressures, and (3) providing optimum rheology byfacilitating concentric expansion and a round lumen.

A lack of effective debulking devices limits a com-plete assessment of a debulking strategy as a preludeto stent deployment. The current “atherectomy” pro-cedures (high-speed rotational atherectomy: Rotabla-tor (Boston Scientific); directional atherectomy: Athe-roCath (Guidant); excimer laser angioplasty andtransluminal extraction: TEC [IVT]) are associated withextensive vessel trauma. Their limited operating sizeprecludes a comprehensive assessment of “adequate”or “complete” debulking. Passage of a 1.5 mm burrhas been widely viewed as “debulking” but does notconstitute effective reduction of plaque mass, in theopinion of the faculty. Debulking is not a “binary”event that follows the passage of a single burr orAtherocath; it is necessarily an iterative processrequiring large devices and a quantitative assessmentof the result.

The routine adoption of a debulking strategyremains unproved and should be the focus of a large-scale randomized trial.

Provisional stentingThe PTCA arm of the BENESTENT II pilot study had

an unusually low restenosis rate (<20%). These favor-

able results in the nonstented arm are thought to be aderivative of more aggressive balloon dilatation strate-gies embraced by interventionists operating in thenewer stent era. With the availability of “stentstandby,” larger balloons and higher pressures areused with the confidence that significant dissectionsand abrupt closures can be easily retrieved and stabi-lized. Accordingly, “stentlike” results may be routinelyachieved with balloon angioplasty alone. In the restric-tive world of cost containment, considerable value hasbeen linked to the strategy of “provisional stenting,”whereby stent usage is reserved for less-than-idealresults from balloon angioplasty—significant dissec-tions or residual stenoses >20%.

The major flaw in the “provisional stenting” para-digm stems from the failure of contrast angiography tofully disclose the extent of residual plaque pathologyafter PTCA. Fig. 13 illustrates apparently “successful”angioplasty results that would be viewed as unfavor-able by intravascular ultrasound criteria.

It is unlikely that “stentlike” results will be achiev-able by balloon angioplasty without the adjunct use ofintravascular ultrasound (IVUS) to assess the result andto aid in determining the requirement for stenting. Therole of IVUS in ensuring “stentlike” angioplasty is cur-rently under study. Subset analyses of data from thesetrials may direct where IVUS will be particularly usefulin determining a treatment strategy, such as in vessels<3 mm or where a large plaque burden exists.

Stenting aortocoronary saphenous vein graftsSuccessful treatment of diseased vein grafts remains

one of the great challenges in interventional cardiol-ogy. The routine use of the Palmaz-Schatz stent andthe Palmaz “biliary” stent has significantly improvedthe acute success of catheter intervention in reversesaphenous vein graft disease.17-20 Major cardiac eventshave been significantly reduced in the group ofpatients who have had vein graft stents.

The faculty agreed that (1) simple vein graft stenosesshould be routinely stented, (2) complex lesions involv-ing organized thrombus should be pretreated withthrombectomy devices (TEC, POSSIS AngioJet [PossisMedical]), and (3) severely degenerated vein grafts can-not be adequately debulked with any of the existentatherectomy devices. Extensive stenting of these oldgrafts is unlikely to eventuate in a durable result.

“No-reflow” after balloon dilatation is rarely correctedby stenting; it may be mitigated by pretreatment withplatelet antagonists (abciximab; ReoPro), though clini-



cal trial data are lacking. No reflow, after stent implan-tation, cannot be predicted by the age of the vein graft;plaque morphology, more than age, appears to be thefactor associated with distal embolization.

The Wallstent has particular promise for use invein grafts. Its availability in flexible long lengths,coupled with greater capacity for coverage, makes itan attractive choice for treating diffuse vein graft dis-ease. Preliminary data suggest that late loss is lesswhen lower pressures are used for deployment ofstents in vein grafts.21

The faculty agreed that stents have improved theacute outcomes of vein graft intervention but are not apanacea. Covered stents may have significant advan-tage in this context.

Stenting small vessel diseaseThe Palmaz-Schatz stent has not been used routinely

in coronary vessels with reference diameters <3.0 mm.Small coronary vessels are structurally different andprobably less forgiving of incomplete stent deploy-ment. Stenting small vessels with devices designed forlarger arteries results in greater metal/tissue surfacecontact, smaller lumens, increased turbulence, a higherthrombosis risk, and greater restenosis.

The manifest need for a small vessel stent has beenhighlighted by the inadequacy of excimer laser angio-plasty and high-speed rotational atherectomy to signifi-cantly attenuate restenosis rates in this anatomic subset.

A fundamental problem that confounds the success-ful treatment of small vessel disease is the difficulty inaccurately defining a “small vessel” by conventionalcontrast angiography. Many “small vessels” turn out tobe >3.0 mm when examined by IVUS. Conversely,many coronary arteries treated with a Palmaz-Schatzstent turn out to be significantly <3.0 mm when objec-tively scrutinized by IVUS or quantitative angiography.

A meta-analysis of the STRESS I and II trials revealedthat >50% of randomly assigned patients had referencevessel diameters <3.0 mm as assessed by qualitativecoronary angioplasty (QCA): 2.69 mm in the stent group(range 2.05 to 2.99 mm) and 2.64 mm in the PTCA arm(range 1.93 to 2.99 mm).22 Abrupt closure was not dif-ferent in this “small vessel” group. Restenosis was 54%for patients with “small vessels” who were randomlyassigned to PTCA and 33% for the stented arm. A furthermetaanalysis, performed on patients with reference ves-sel size <2.6 mm as compared with <3.0 mm, failed todemonstrate a restenosis benefit from stenting (M. Leon,personal communication); however, it should be empha-

sized these data stem from use of a stent that was notdesigned for small vessels. Simple balloon angioplasty isintrinsically more efficient in smaller vessels, and it mayprove difficult to demonstrate a beneficial effect fromstenting in this clinical context.

The NIR, BeStent, and AVE Microstent may be moresuitable for small vessel disease. Cordis/Johnson &Johnson has plans to introduce a small “baby crownstent” explicitly for use in small vessels. Randomizedtrials with the 2.5 mm GR II (Cook, Inc.) and the AVEMicrostent stent in small vessels are underway.

There was consensus among the faculty that thevalue of small vessel (<2.5 mm) stenting remainsunknown, awaiting resolution with newer stentdesigns (possibly including novel coatings), large-scaleregistries, and randomized clinical trials.

Stenting ostial stenosesStents have been routinely deployed at the aorto-

ostial junctions of the right coronary artery and saphe-

Figure 11

Incomplete coverage of plaque, particularly at apexes of bifur-cation, is significant limitation of coil stents. (Modified fromdrawings of Dr. Ian Penn and used with permission.)

High-pressure deployment of a stent at the ostium ofthe left anterior descending coronary artery can lead tocompression of the proximal circumflex, particularlywhen there is a large burden of plaque at the stent site.In such situations, it may be desirable to debulk the leftanterior descending artery before stenting, facilitatingdeployment at lower pressures and mitigating the com-pressive effect on the adjacent circumflex origin.

Many members of the faculty expressed a preferencefor directional coronary atherectomy (DCA) as an ini-tial approach to ostial stenoses, reserving stents forpatients who developed restenosis.

Left main coronary artery stentingStenting “unprotected” left main coronary artery dis-

ease, in the absence of a patent graft to the anteriordescending or circumflex artery, has been widelyviewed as unduly dangerous and thus rarely performedin the United States. Although the acute results arehighly successful and usually accomplished with techni-cal ease, the occurrence of late death is reportedly high.Ellis et al.23 at the Cleveland Clinic analyzed a registry ofpatients who had received stents in “unprotected” leftmain disease and discovered a 19% incidence of deathat 6 months. Many of these deaths are suspected to haveresulted from global ischemia after high-grade resteno-sis. Restenosis in the left anterior descending, circumflex,or right coronary artery is usually heralded by recurrentangina. Presumably the greater extent of ischemiaattending restenosis in the left main is more likely toprecipitate lethal ventricular rhythm disturbances.

Left main coronary artery disease is not a singledisease entity. Various patterns of left main diseasepresent unique challenges for intervention and stent-ing. Ostial disease of the left main artery requires adifferent treatment strategy than isolated diseasewithin the mid vessel or distal vessel. Trifurcationdisease, extending from the left main artery into theanterior descending and proximal circumflex arteries,is probably beyond the reach of current stent tech-nology.

Many in this experienced faculty argued that onecould be more sanguine about stenting “unprotected”left main disease in 1997 when subacute thrombosisrates are <1% and restenosis rates for larger (3 to 4mm) vessels are in the range of 10% to 15%; othersasserted that the presentation of restenosis in the leftmain artery is so unpredictable and potentially lethalthat elective left main stenting should be avoided.

Although frequently performed in many countries,


nous vein grafts and at the ostium of the left anteriordescending coronary artery. Routine stenting of the cir-cumflex ostium has been less frequently used becauseof its acute angulation off the left main coronary artery.

Stents capable of providing significant radial force(eg, Palmaz-Schatz and Palmaz “biliary” stents) arebelieved to be of particular value for ostial stenting.

The ideal stent for ostial deployment should behighly visible, facilitating precise placement. The Pal-maz “biliary” stent is among the most visible of rou-tinely used stents and is thus a favored device foraorto-ostial stenting.

Proximal and distal edge markers (such as seen onthe GR II) can further facilitate precise placement atostial locations, thus avoiding compromise of the leftmain, coverage of the circumflex origin (in ostial leftanterior descending disease), or extension into theaorta (with ostial right coronary artery or vein graftstenoses). Coil stents, however, are generally deemedsuboptimal for ostial stenting, in which stents withmaximal radial strength are a more appropriate choice.

Figure 12

Attempts to treat bifurcation stenoses with rigid, slotted tubularstents are frequently compromised by failure to cover allaspects of pathology. A half stent is commonly used for branchdisease. (Modified from drawings of Dr. Ian Penn and usedwith permission.)

stent deployment in the unprotected left main arterywas viewed by the majority of the faculty to be anunproved application with distinctive potential for seri-ous adverse outcomes.

Is high-pressure deployment of stents a necessaryroutine?

A broad experience with the Palmaz-Schatz stent ledoperators to conclude that high-pressure dilatation isgenerally obligatory after initial deployment with theconventional Johnson & Johnson delivery system.IVUS studies have demonstrated that incomplete appo-sition and underexpansion are common in the absenceof high-pressure stent deployment.

A variety of noncompliant balloons are available tofacilitate full deployment of the Palmaz-Schatz stent.These balloons are uniformly flawed by poor rewrap-ping characteristics, and it is usually necessary toremove and manually rewrap the balloon beforereuse. “Winging” of the deflated balloon material canalso lead to entrapment of the deflated balloon withinthe stent. Many European investigators have switchedto “semicompliant” balloons for stent deploymentbecause of their more favorable rewrapping character-istics. Semicompliant balloons are less ideal for very

high-pressure deployment (16 to 20 atm); however, itis uncertain that it is the “high pressure” rather than anappropriate cross-sectional area of the balloon thatwill be as important for the next generation of stents.

Although full stent expansion and complete apposi-tion appear to be associated with less acute and suba-cute thrombosis, high-pressure stent deployment canlead to deeper media damage, hence, greater late loss.It is possible that lower-pressure dilatation and moreappropriate upsizing of balloons may enable maximalstent expansion without the same degree of trauma tothe vessel wall. The balance between optimizing stentexpansion and minimizing the injury of deploymentshould be the focus of immediate clinical investigation.

Adjunct pharmacologic support of stentingAspirin has been shown to be therapeutic and cost

effective in preventing acute and subacute occlusionsafter coronary dilatation procedures and is routinelygiven before and after coronary angioplasty.24 Ticlopi-dine, in addition to aspirin therapy, likewise signifi-cantly reduces target vessel revascularization, Q-wavemyocardial infarction, or death after coronary stentingwhen compared with aspirin alone and aspirin pluscoumadin therapy (8.2% vs 12.4%, P = .01).25 The


Figure 13

Excellent angiographic result after balloon angioplasty in proximal right coronary artery. Intravas-cular ultrasound, however, shows significant discrepancy, including large plaque residual (A), cal-cium-associated dissection (B), and superficial calcium (C).

MIDCAB/stent synergyMinimally invasive direct coronary artery bypass

(MIDCAB) surgery has rapidly evolved with a series ofdifferent techniques. Internal thoracic pedicle graftsare now routinely anastomosed to anterior coronaryvessels without the use of cardiopulmonary bypass.Although “minimally invasive” techniques have beendeveloped for surgery on an arrested heart (by usingpercutaneous bypass),29 the bulk of MIDCAB opera-tions are completed on a beating heart without the useof cardiopulmonary bypass.30,31 Routine access to theposterior circumflex and the distal right coronary arter-ies is not feasible with most beating heart techniques.

The potential synergy of MIDCAB with stenting formultivessel coronary artery disease has been advo-cated by many cardiologists. In this collaborativescheme, arterial grafting of the left anterior descend-ing artery is conceded to the cardiovascular surgeons,with cardiologists performing adjunct stenting of theposterior, inferior, and lateral circulation as a stagedor concomitant procedure. The combination of MID-CAB and percutaneous stenting can obviate the use ofa vein conduit with its inherent problems of earlydegeneration.


addition of ticlopidine therapy for 2 to 4 weeks aftersuccessful stenting is advocated. There are few clinicalstudies supporting the routine use of other adjunctpharmacologic agents before, during, or after thedeployment of intracoronary stents.

Restenosis is a complex response to injury. If oneaccepts that the first element of the response is throm-bosis at the site of injury, then one might predict thatplatelet antagonists such as abciximab (Reopro) wouldhave a significant impact on intrastent restenosis. Lateresults from the EPIC trial, in which abciximabreduced ischemic events at 6 months by 23%, tend tosupport this assertion.26

Although stents can substantially attenuate the con-tributions of recoil and shrinkage to restenosis,incomplete coverage of the exposed plaque leaves aclear pathway for smooth muscle cell migration andproliferation. Early reports of radiation strategieswith beta-particle–emitting stents or brachytherapywith either beta or gamma radiation suggest signifi-cant reductions in restenosis rates.27,28 A local phar-macologic radiation therapy or a combination ofboth may be required to fully abolish intrastentrestenosis.

Figure 14

Ostial encroachment in left circumflex artery (LCx) after placement of stent in ostial portion of left ante-rior descending (LAD) artery. Multiple angiographic views were taken in an effort to place stent distalto take-off of circumflex artery. Intravascular ultrasound shows that circumflex artery was “jailed.”

The real potential of MIDCAB/stent synergy mustnecessarily be reconciled in an economic context. Thequestion of whether these complementary procedureswill be more durable and cost effective when com-pared with conventional aortocoronary bypass surgeryis as yet unknown.

Stent imagingAlthough coronary angiography has long been the

standard for coronary stenosis assessment, it remains alimited means of assessing the acute stent result. IVUSprovides additional information that may assist stentimplantation. Particular advantages of IVUS over stan-dard contrast angiography include (1) preintervention:determination of reference vessel size and presence ofdisease, accurate assessment of lesion length, potentialto help direct other catheter-based prestent treatments(such as debulking) or poststent pharmacologic thera-pies and (2) poststent deployment (with or withoutadjunct PTCA): IVUS may enable stent placement,stent expansion, stent/vessel wall apposition, and stentmargin dissection recognition.

Despite extensive operator experience, high-qualityfluoroscopy, and the routine use of adjunct high-pres-sure PTCA, many stents are still improperly implanted.The routine use of IVUS after stenting has revealedinadequacies of stent deployment not apparent by con-trast angiography, including (1) lesion borders missed,(2) ostium not covered by the stent, (3) major branches


covered (eg, origin of left circumflex), (4) stents“squashed” to one side (presumably by rewiring a ves-sel and going around instead of through a stent), and(5) incomplete expansion (see Figs. 14 through 16).

Uren et al.32 retrospectively reviewed the IVUSrecordings of 57 patients who subsequently developedsubacute closure after stent deployment. In 90% ofcases they identified an IVUS abnormality includingincomplete apposition, incomplete expansion, prob-lems at the stent margins, and inflow or outflow dis-ease. These findings, clearly demonstrated by IVUS,were rarely recognized by concomitant angiography.Nevertheless, the routine use of IVUS after PTCA andbefore coronary stenting remains contentious. Fitzger-ald et al.33 demonstrated that the most significant pre-dictors of restenosis are residual percent plaque areaand minimal lumen diameter (MLD) as assessed by

Table II .

Figure 15

Example of unsuccessful rewiring of unexpanded stent resulting in wire being next to partially crushedstainless-steel stent.

IVUS. They propose that the combination of a residualplaque area <65% and an MLD >2.0 mm is predictiveof a successful long-term outcome in the absence ofstenting. Thus these IVUS end points could be reason-ably applied in an ultrasound-derived pathway forprovisional stenting (Table II).

The routine use of IVUS during stenting probablywould have less effect on subacute thrombosis (inwhich the event rate may be too low to demonstratea benefit for this end point) than on restenosis. TheAVID,34 CRUISE,35 and MUSIC36 trials showed thatIVUS guidance can facilitate a larger final stent area,with an overall gain of 1 mm2 compared withdeployment by using angiography alone. Two sin-gle-center studies have recently confirmed that thereis a direct relation between minimum stent area andthe incidence of instent restenosis and target vesselrevascularization.37,38 The suggestion that IVUS-guided stenting may translate into reduced resteno-sis rates is clear. However, the potential benefit ofIVUS-guided stent deployment must be balancedwith the added cost of ultrasound imaging. The costof performing IVUS is a moving target that is coun-try specific. In the United States, the cost of an IVUScatheter is less than a stent. In Europe, the cost ofan IVUS catheter approaches and, in some coun-tries, exceeds that of commonly used stents.Although the price of IVUS catheters may come


down, their routine use as a cost-effective strategy isyet to be proved.

The majority of the summit attendees do not rely onIVUS to guide their stent deployments; however,those centers with the greatest IVUS experience (Stan-ford, Milan, and the Washington Hospital Center)have continued to depend on ultrasound guidance forvirtually all of their cases. The role of IVUS in routinecoronary stenting remains debatable and clearlyrequires further definition.

Intrastent restenosisThe widespread application of coronary stents has

precipitated a new clinical challenge for intervention-ists—intrastent restenosis. The BENESTENT andSTRESS trials demonstrated significant reduction in theincidence of restenosis after stenting of de novo coro-nary lesions; however, there was at least a 20% to 30%occurrence of intrastent restenosis in these trials.These large randomized trials were limited to simplelesions with single stents in relatively large vessels. Itappears that the increasing use of stents in ostial loca-tions and in small vessels along with the application ofmultiple stents in long lesions eventuates in evenhigher rates of intrastent restenosis.

Intrastent restenosis is seen with variable morphol-ogy and topography including proliferation at the mar-gins of the stent, at the articulation (with the Palmaz-

Figure 16

Angiographically successful stent deployment in circumflex artery. Intravascular ultrasound reveals incom-plete apposition shown between 4 and 8 o’clock positions, with struts unapposed to intimal surface.

Schatz stent), focally within the stent, and diffuselythroughout the stent.

Simple balloon angioplasty of intrastent restenosisrarely recaptures the MLD that was achieved at thetime of initial stent deployment; thus recurrence ratesare high. IVUS and angioscopic assessment suggest thatthe neointima of intrastent restenosis is extruded backthrough the stent lattice during high-pressure ballooninflation and that some of this extruded material imme-diately returns. In intrastent restenosis, IVUS studiessuggest that approximately half of the gain is achievedby extrusion of the neointima through the struts andthe remainder through further stent expansion.39

The majority of intrastent restenoses are diffuse;most of the summit faculty agreed that some sort ofdebulking procedure is desirable before PTCA of therestenotic narrowing. Debulking is particularly desir-able in self-expanding stents such as the Wallstent,which cannot be further reexpanded by balloon dilata-tion at the time of retreatment. Excimer laser angio-plasty has been advocated as a logical application ofthis ablative atherectomy device. A multicenter trial(LARS) is planned to address the relative value ofexcimer debulking compared with simple balloonangioplasty for intrastent restenosis.

High-speed rotational atherectomy (HSRA, Rotabla-tor), as an intrastent debulking procedure, has beenadvocated by many of the faculty because of their per-ception that it is more efficient. A randomized trial(TWISTER) will compare high-pressure balloon treat-ment of intrastent restenosis with a combinedapproach of HSRA with PTCA.

Local intracoronary radiation (brachytherapy) withgamma and beta emitters has recently received signifi-cant attention despite limited application. Teirsteinreported preliminary data from a small number ofpatients with intrastent restenosis who appear to havebenefited from intrastent brachytherapy after balloonangioplasty of intrastent restenosis.40

A low-dose, beta-emitting stent (Isostent [Cordis])has been developed as a primary approach to prevent-ing intrastent restenosis. Limited animal investigationsuggests that this 32P-coated stent has the potential tosubstantially abolish the proliferative response that isroutinely incited by full stent.41-43 The ultimate safetyand efficacy of this strategy will clearly need furtherdefinition from randomized clinical trials that haverecently started.

With nearly 50% of interventional procedures involv-ing stents, the challenges of prevention and treatmentof intrastent restenosis have emerged as major targetsof clinical investigation. The relative importance ofdebulking, coatings, coverings, and adjunct pharma-ceutical treatments will require large registries and insome instances, randomized clinical trials for greaterdelineation.

Noncoronary stentingStents are extensively used outside of the coronary

circulation. Interventional radiologists and cardiologistshave effectively used stents in a variety of vascular andnonvascular applications, including iliac, renal, aorta,brachycephalic and carotids, femoral-popliteal, andtransjugular intrahepatic portosystemic shunts (TIPS).

Iliac stentsThe positive impact of stent implantation has been

most dramatic in the iliacs in which simple balloonangioplasty (PTCA) has had historical patency rates of


Age 35 to 89 yearsCoronary artery disease 80%Carotid vessels treated 252Symptomatic 150 (61 strokes, 89 transient

ischemic attacks)Asymptomatic 102Stent types

Balloon expandable 203 JJ (biliary 165), Cook 38Self-expanding (Schneider Wallstent)

Table III. Carotid stenting

Technical success (233/236 [98.7%])Inability to access carotid

through femoral artery 2Air embolus during

baseline angiography 1Acute complications

Death 1 (retroperitoneal hematoma)Major stroke 2 (0.7% of vessels treated)Minor stroke 16 (6% of vessels treated)Stent thrombosis 1

Table IV. Carotid stenting

Death 10 (1 from cerebral bleed,others cardiac/pneumonia)

Transient ischemic attack 4Surgical endarterectomies 2Stent deformation 9

Table V. Carotid stenting: Clinical follow-up

approximately 75% at 5 years and 60% to 70% at 10years.44 The use of Johnson & Johnson Palmaz stents inthe iliacs has improved long-term patency rates to near90%.45 The results in the superficial femoral arteries havebeen less attractive with significant restenosis rates.

Carotid stentsCarotid angioplasty has emerged as a competitive

alternative to conventional surgical endarterectomy forsymptomatic occlusive disease of the common andinternal carotid artery. Stents have gradually become aroutine adjunct to PTCA of the carotid.

At the Stanford Stent Summit, Dean reported on aconsecutive series of 216 patients who underwentcarotid stenting at the University of Alabama fromSept. 1, 1994, through Oct. 31, 1996 (L. Dean, personalcommunication). Their results are summarized inTables III through V.

The concern over stent deformation was a criticalfactor that led to a change from the Palmaz “biliary”stent to the Schneider Wallstent for routine use incarotid stenting at the University of Alabama. It ispossible that some of the cases of stent deformationmay have derived from ultrasound examination infollow-up or from compression against the spinewith movement of the neck. The more flexible self-expanding Wallstent should mitigate the incidenceof this important limitation seen with the biliarystent.

The Wallstent may not be the perfect stent for use inthe carotids. It is long (covering the external carotid),with a significant metal/tissue interface. The edges aresharp and the delivery system is not ideal.

The 9F guiding catheters, commonly used for carotidstenting, are clearly inadequate and a frequent source oftechnical difficulty because they were primarily designedfor coronary use. Newer 7F sheath designs haveimproved the overall performance of carotid stenting.

Despite the widespread enthusiasm for carotid stent-ing, a relatively small number of cases has been com-pleted by a very select group of interventionists. It isclear that both the carotid stent and the delivery sys-tem need substantial improvement. Mainstream adop-tion of this procedure will unquestionably require awell-designed randomized clinical trial comparingPTCA with surgical endarterectomy.

Stent graftsThe use of covered stents (stent grafts) is more com-

mon in the periphery, where larger delivery profiles are

less of an issue. Aortic stent grafts are widely used in thedescending and abdominal aorta to exclude aneurysmswithout the need for open thoracotomy or laparotomy.

Stent grafts have significant potential for routine usein TIPS procedures. Bile leaks into the stented shuntare commonly encountered and profoundly thrombo-genic. A covered stent, deployed in the shunt, wouldpotentially exclude the bile leak and preserve thepatency of the intrahepatic portocaval shunt.

Summary: Stent trials in the nextdecade

The faculty agreed that further randomized clinicaltrials are probably unnecessary to confirm the effec-tiveness of derivative slotted tubular and expandablecoil stent designs. Multiple iterations of these designshave demonstrated efficacy in native coronary arteries,typically with delivery failure <3%, subacute thrombo-sis rate with aspirin and ticlopidine <1%, MACE (majoradverse cardiac events) at 30 days <5%, QCA resteno-sis rate <25%, and target lesion revascularization <15%.

The faculty agreed that stents of similar design,meeting these benchmarks, should not require ran-domization against balloon angioplasty or the Johnson& Johnson Palmaz-Schatz stent as a condition forapproval by the Food and Drug Administration; a thor-ough registry analysis should suffice.

Could a derivative stent be labeled for use in aorto-coronary vein grafts, restenotic lesions, abrupt orthreatened closure without a randomized clinical trial?The faculty responded yes, if a reasonably scaled reg-istry (eg, 200 patients) documented adverse outcomesthat were not >50% of those seen with elective use inde novo lesions.

The question of whether it is reasonable to introducevariable stent lengths shorter and longer than 15 mmand expanded diameters greater than 4 mm withoutextensive randomized trials was addressed at the meet-ing. The summit faculty believed that stent lengths inthe range of 9 to 40 mm and diameters up to 6 mmcould be approved on the basis of registry data alone.

Significant stent modifications and expanded clinicalapplications probably will require full randomized clini-cal trials before receiving premarket approval from theUnited States Food and Drug Administration. It isexpected that randomized clinical trials will still berequired for (1) novel stent designs, for example, sheetdesigns, (2) new stent materials (the majority of stents inclinical use rely on stainless steel) (new materials such


as nitinol and polymers are unproved in terms of safetyand efficacy), (3) stent/drug combinations, drug deliverystents, (4) radioactive stents, and (5) new indications forstent deployment: acute myocardial infarction, small(<2.5 mm) vessels, bifurcations, unprotected left maindisease, carotid disease, and intrastent restenosis.

Many of these “newer” indications cannot be reliablyexplored with registry data because of limited compa-rable experience with the Johnson & Johnson Palmaz-Schatz stent.

Knowledge of stent-tissue interaction is incomplete.The pathophysiological consequences of balloonexpansion versus self-expansion remain undefined.The routine use of high pressures for stent deploymentevolved without a full understanding of the long-termresults or variability between stents. Immediate post-stent data have been carefully gathered, but late sur-veillance data after stent deployment are incomplete.There is minimal insight in regard to the long-termimpact of implanting a rigid stent implantation on thesurface of a vigorously contractile heart, and it isunknown whether issues of erosion, migration, andmetal fatigue emerge to haunt the next stent decade.

New stent designs should be evaluated by protocolthat mandates limited postmortem examination ofstented vessels so that we can learn more about theultra long-term consequences of stent implantation. Itis clear that this type of insight will not come from ani-mal surrogates but ultimately from human beings.

In summary, the first stent decade established thesafety and efficacy of intracoronary stents as anadjunct to balloon angioplasty for de novo lesions innative coronary arteries and aortocoronary vein grafts.Numerous “off-label” applications received generalacceptance without validation by a large clinical trial.

The Stanford Stent Summit faculty reached a consen-sus opinion on the role of coronary stenting in variousclinical scenarios. The use of debulking before stentdeployment was thought to be favorable in ostial dis-ease and with complex bifurcation stenoses or diffusecalcified coronary disease. When percutaneous treat-ment of saphenous vein grafts is to be undertaken,stenting was routinely advised. Unprotected left maincoronary stenting was viewed as an unproved, high-risk procedure and not generally recommended by thefaculty. Although metaanalyses of stent trials suggestedbenefit of stenting in small vessels <3.0 mm in diame-ter, the faculty agreed that clinical trials addressingsmall vessel disease are required before stentingshould be routinely recommended for this indication.

There was agreement that IVUS provides additionalinformation over standard coronary angiography, withparticular advantages related to determination of ves-sel size, lesion length, adequacy of plaque coverage,and stent deployment and expansion or the presenceof dissection. The role of IVUS and a provisional stent-ing algorithm with the use of ultrasound-determinedcriteria was discussed. The faculty concluded that fur-ther studies are required to fully define the therapeuticand cost benefits of such a strategy.

The routine use of aspirin and ticlopidine in coro-nary stenting was strongly recommended by the fac-ulty. Intrastent restenosis was highlighted as the major“bugbear” of current stenting techniques, with adjunc-tive pharmacologic therapies such as abciximab (Reo-pro) noted to impact favorably on clinical outcomeafter coronary stenting.

Although early studies of intracoronary radiationtherapy appear to show a reduction in intrastentrestenosis, the faculty agreed that this treatmentrequires further studies to fully define efficacy andlong-term safety. To date, carotid artery stenting hasbeen performed only by a select group of interven-tionalists, and widespread use of this technique awaitstrials comparing results with surgical endarterectomy.

Finally, the Stanford Stent Summit faculty identified amultitude of engineering, technical, and clinical chal-lenges awaiting resolution in the second stent decade.Important challenges for clinical research include (1) afuller understanding of the impact of various stentdesigns on deployment strategies, anticoagulationrequirements, and long-term stent—tissue interaction,(2) the role of stenting in expanded lesion subsets:small vessels (<2.5 mm), long lesions/diffuse disease(requiring coverage >20 mm), bifurcation stenoses,unprotected left main disease, and acute thromboticmilieu (eg, acute myocardial infarction), (3) the role ofstent registries as an alternative to costly randomizedclinical trials, (4) application of stents into newanatomic frontiers: carotids, renals, aorta, and smallvessel peripheral vascular disease, (5) potential ofstent graft prostheses (“covered stents”), (6) primaryprevention and secondary treatment of intrastentrestenosis: coated stents, radioactive stents, stents as aplatform for small molecule and gene transfer, and (7)influence of operator technique: stent location and siz-ing, deployment strategies (predilatation, debulking,high pressure), and approach to bifurcations, ostialstenoses, and chronic total occlusions, (8) clarificationof the role of “provisional” stenting, (9) a more com-



plete analysis of costs and benefits, particularly in thetreatment of multivessel coronary artery disease, (10)most appropriate method of stent assessment: IVUS,pressure and flow wires, and QCA, (11) relative role ofstents in the context of emerging technologies (eg,MIDCAB, brachytherapy)—competitive, complemen-tary, or synergistic, and (11) ultra long-term (>5 to 10years) analysis of stent/tissue/coronary interaction.

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25. Kuntz RE, Baim DS, Popma JJ, Ho KK, Senerchia C, Fitzpatrick M, etal. Late clinical results of the stent anticoagulation regimen study(STARS) [abstract]. Circulation 1997;96(suppl I):I-594.

26. Topol EJ, Califf RM, Weisman HF, Ellis SG, Tcheng JE, Worley S, etal., for the EPIC Investigators. Randomised trial of coronary inter-vention with antibody against platelet IIb/IIIa integrin for reductionof clinical restenosis: results at six months. Lancet 1994;343:881-6.

27. Baim DS, Fischell T, Weissman NJ, Laird JR, Marble SJ, Ho KK. Short-term (1 month) results of the RIS feasibility study of a beta-particle emit-ting radioisotope stent [abstract]. Circulation 1997;96(suppl I):I-218.

28. Russo RJ, Massullo V, Jani SK, Schatz RA, Guarneri EM, SteutermanS, et al. Restenting versus PTCA for in-stent restenosis with or withoutintracoronary radiation therapy: an analysis of the SCRIPPS trial[abstract]. Circulation 1997;96(suppl I):I-219.

29. Stevens JH, Burdon TA, Peters WS, Siegel LC, Pompili MF, VierraMA, et al. Port-access coronary artery bypass grafting: a proposedsurgical method. J Thorac Cardiovasc Surg 1996;111:567-73.

45. Palmaz JC, LaBorde JC, Rivera FJ, Encarnacion CE, Lutz JD, MossJG, et al. Stenting of the iliac arteries with the Palmaz stent: experi-ence from a multicenter trial. Cardiovasc Intervent Radiol1992;15:291-7.

Stanford Stent Summit facultyYaron Almagor, Shaare Zedek Medical Center,

Jerusalem; Donald Baim, Beth Israel Hospital, Boston;Maurice Buchbinder, Sharp Memorial Hospital, SanDiego; Antonio Colombo, Columbus Hospital-Milan,Lennox Hill, New York; Michael Dake, Stanford Uni-versity; Larry Dean, University of Alabama, Birming-ham; Peter Fitzgerald, Stanford University; HermanGold, Massachusetts General Hospital, Harvard Med-ical School, Boston; Sheldon Goldberg, MassachusettsGeneral Hospital, Harvard Medical School, Boston;Eberhard Grube, Sieburg, Germany; Tomako Hino-hara, Stanford University; Richard Kuntz, Beth IsraelHospital, Harvard Medical School; Martin Leon, Wash-ington Hospital Center; Gary Mintz, Washington Hos-pital Center; Michael Mooney, Minneapolis Heart Cen-ter; Marie Claude Morice, Clinique du Bois deVerrieres, Antony, France; Stephen Oesterle, StanfordUniversity; Ian Penn, Vancouver, British Columbia,Canada; Augusto Pichard, Washington Hospital Cen-ter; Steven Ramee, Ochsner Clinic, New Orleans;Nicolaus Reifart, Red Cross Hospital and FrankfurtHeart Center, Frankfurt, Germany; Robert Schwartz,Mayo Clinic, Rochester, Minn.; Ulrich Sigwart, RoyalBrompton National Heart and Lung Hospital, London;John Simpson, Stanford University; Richard Stack,Duke University, Durham, N.C.; Simon Stertzer, Stan-ford University; Renu Virmani, Armed Forces Instituteof Pathology, Washington, D.C.; Patrick Whitlow,Cleveland Clinic Foundation; Tetsu Yamaguchi,Ohashi Hospital, Tokyo, Japan; Alan Yeung, StanfordUniversity; Paul Yock, Stanford University; BramZuckerman, United States Food and Drug Administra-tion, Washington, D.C.


30. Arom KV, Emery RW, Nicoloff DM. Mini-sternotomy for coronaryartery bypass grafting. Ann Thorac Surg 1996;61:1271-2.

31. Calafiore AM, Angelini GD, Bergsland J, Salerno TA. Minimally inva-sive coronary bypass grafting. Ann Thorac Surg 1996;62:1545-8.

32. Uren NG, Schwarzacher SP, Metz JA, Alderman EL, Abizaid A,Fitzgerald PG, et al., for the POST Registry. Intravascular ultrasoundprediction of stent thrombosis: insights from the POST registry[abstract]. J Am Coll Cardiol 1997;29(suppl A):60A.

33. The GUIDE Trial investigators. IVUS-determined predictors ofrestenosis in PTCA and DCA: final report from the GUIDE trial,phase II [abstract]. J Am Coll Cardiol 1996;27(2):156A.

34. Russo RJ, Nicosia A, Teirstein PS, for the AVID investigators. Angiog-raphy versus intravascular ultrasound-directed stent placement[abstract]. J Am Coll Cardiol 1997;29(suppl A):60A.

35. Metz JA, Fitzgerald PJ, Osha A, Hayase M, Weissman NJ, DiverDJ, et al. Impact of intravascular ultrasound guidance on stenting inthe CRUISE substudy [abstract]. Circulation 1996;94:I-199.

36. Mudra H, Sunamura M, Figulla H, Almagor Y, Bilodeau L, Penn I, etal., MUSIC study investigators. Six month clinical and angiographicoutcome after IVUS guided stent implantation [abstract]. J Am CollCardiol 1997;29(suppl A):171A.

37. Akiyama T, Dimario C, Reimers B, Ferraro M, Moussa FI, BlenginoS, et al. Do we need intracoronary ultrasound after high pressurestent expansion [abstract]? J Am Coll Cardiol 1997;29(A):59A.

38. Kim MH, Ziada K, DeFranco A, Raymond R, Whitlow PL, Ellis SG, et al.“Step-up” or “step-down” in small stented vessels does not adverselyimpact clinical outcome [abstract]. J Am Coll Cardiol 29(A):279A.

39. Mehran R, Mintz GS, Popma JJ, Hong MK, Laird JR, Satler LF, et al.Treatment of in-stent restenosis: an intravascular ultrasound study ofresults in 159 stented lesions [abstract]. J Am Coll Cardiol 1997;29(suppl A):77A.

40. Teirstein PS, Massullo V, Jani S, Popma JJ , Mintz GS, Russo RJ, etal. Catheter based radiotherapy to inhibit restenosis after coronarystenting. N Engl J Med 1997;336:1697-703.

41. Laird JR, Carter AJ, Kufs WM, Hoopes TG, Farb A, Nott SH, et al.Inhibition of neointimal proliferation with low-dose irradiation frombeta-particle-emitting stent. Circulation 1993;93:529-36.

42. Carter AJ, Laird JR, Bailey LR, Hoopes TG, Farb A, Fischell DR, et al.Effects of endovascular radiation from a beta-particle emitting stentin a porcine coronary restenosis model: a dose-response study. Cir-culation 1996;94:2364-8.

43. Rivard A, Leclear G, Bouchard M, Beaudoin G, Carrier R, JanickiC, et al. Low-dose β-emitting radioactive stents inhibit neo-intimalhyperplasia in porcine coronary arteries: a histological assessment.J Am Coll Cardiol 1997;29(suppl A):238A.

44. Becker GJ, Katzen BT, Dake MD. Noncoronary angioplasty. Radiol-ogy 1989;170:403-12.

the stent decade: 1987 to 1997

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