Stenting in coronary angioplasty

Stenting in coronary angioplasty

Jeptha P. Curtis, John F. Setaro

Introduction

The introduction of stents stands as one of the truly revolutionary steps in the history of inter- ventional cardiology. Since worldwide approval of the balloon-expandable Palmaz–Schatz stent, the use of stents has become a routine part of percutaneous coronary interventions (PCI).

In 2002 it was estimated that stents are used in more than 80% of all coronary interventions at a cost of over 1.6 billion dollars in the USA alone. These numbers do not factor in the increased costs associated with drug-eluting stents. Clearly stents have had a profound impact on the contemporary practice of interventional cardiology. This chapter will review the studies that served as critical steps in the development and adoption of coronary stents.

The term “stent” is thought to come from the English dentist, Charles R. Stent, who developed a method of supporting misaligned teeth. Subsequently, stent (having permanently lost its cap- italization) was adopted by surgeons to describe any device designed to support a bodily orifice or cavity during skin grafting or to immobilize a skin graft following placement. In modern medical literature, the definition of stent has come to encompass all hollow devices inserted into the tubular structures in order to provide support and maintain patency.

Drs Dotter and Judkins initially proposed the development of intravascular stents in their seminal 1964 paper, “Transluminal Treatment of Arteriosclerotic Obstruction”. After describing the results achieved by serial coaxial arterial dilatations, they envisioned the use of an “endovascular (or, paravascular) splint [that] could maintain an adequate false lumen until the natural processes of fibrosis and re-intimalization had taken place”. Although it took only 5 years for Dr Dotter to implant coilspring tubes in canine femoral arteries, it would take almost two decades before technological innovations allowed the successful implantation of expandable metal stents in human arteries.

The need for intracoronary stents was driven by the two persistent limitations of balloon angioplasty, namely restenosis and acute closure. In the pre-stent era, acute closure due to dissection or residual stenosis led to emergency bypass surgery in more than 1% of patients.

Furthermore, 30–50% of patients had symptomatic restenosis requiring repeat interventions.

Stents were unique among advanced interventional devices, having a capability to address both problems simultaneously. In cases of threatened acute closure, interventionalists could use stents to tack up a dissection flap. In addition, the greater acute gain in luminal diameter associated with the use of coronary stents led to clinically and statistically significant reduc- tions in need for revascularization due to restenosis. Once approved for elective use in coro- nary interventions, the floodgates opened and stents swiftly became the rule rather than the exception.

Subsequent studies demonstrated the utility of stents in a variety of patients and lesion sub- groups including acute myocardial infarction, diabetics, total occlusions, saphenous vein grafts, and long lesions. Simultaneously, stent manufacturers have continuously improved their tech- nology, creating stents with thinner struts, increased radial support, and improved deliverability.

Undoubtedly the most important advance since the original introduction of coronary stents has been the development and approval of drug-eluting stents which have dramatically decreased the incidence of clinical and angiographical restenosis.

Collectively, these advances have allowed interventional cardiologists to approach higher-risk patients, and fewer patients are being sent for surgery or treated medically. This shift has led critics to question whether interventional cardiologists have gone too far and routinely use stents in situations where there is limited or no evidence of benefits associated with stent implantation. If there is truth to these charges, the challenge to interventional cardiologists will be to balance current evidence with the desire to advance the field of coronary intervention.

Title 1

Transluminally-placed coilspring endarterial tube grafts:

long-term patency in canine popliteal artery

Author

Dotter CT

Reference

Invest Radiol 1969; 4: 329–332

Abstract

Tubular prosthetic grafts introduced via carotid arteries were placed transluminally in femoral- popliteal arteries in 25 dogs using simple catheter techniques. While various impervious plastic tubes clotted promptly, the adoption of an open coilspring configuration has made possible long-term patency. Advantages of this potentially useful approach include freedom from the trauma usually associated with surgical vascular reconstruction.

Summary

In this paper, Dr Dotter presents his group’s technique for the percutaneous transluminal placement of tubes in 25 undiseased canine arteries. While procedural success rate was high, maintaining patency proved difficult due to early thrombus formation. This was universally true in the 19 dogs who received plastic tubes, all of which clotted within 24 h. More promising was the experience of “coilspring tubular prosthethes” implanted in six dogs. These devices consisted of wound no. 5 gauge stainless-steel wire ranging in length from 1 to 10 cm. Heparin was given during stent implantation and continued for 4 days or until occlusion occurred.

No antiplatelet therapies were employed. Of the metal prostheses implanted, three had occluded at 24 h. However, two stents remained patent for more than 2 years on follow-up angiography.

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Related References

1. Dotter CT, Judkins MD. Transluminal treatment of arteriosclerotic obstruction. Description of a new technic and a preliminary report of its application. Circulation 1964; 30: 654–670.

2. Dotter CT, Buschmann RW, McKinney MK, Rosch J. Transluminal expandable nitinol coil stent grafting: preliminary report. Radiology 1983; 147: 259–260.

3. Cragg A, Lund G, Rysavy J, Castaneda G, Castaneda-Zuniga W, Amplatz K. Nonsurgical placement of arterial endoprostheses: a new technique using nitinol wire. Radiology 1983; 147:

261–263.

4. Palmaz JC, Sibbett RR, Reuter SR, Tio FO, Rice WJ. Expandable intraluminal graft: a pre- liminary study: work in progress. Radiology 1985; 156: 73–77.

5. Wright KC, Wallace S, Charsangavej C, Carrasco CH, Gianturco C. Percutaneous endovas- cular stents: an experimental evaluation. Radiology 1985; 156: 69–72.

Key message

This brief report was the first demonstration of the technical feasibility of transluminal tube placement in arterial vasculature. This paper also identified the importance of thrombus forma- tion and established stainless steel as the preferred material for endovascular prostheses.

Perhaps most exciting, Dr Dotter demonstrated the potential for long-term patency associated with these tubes.

Why it’s important

This paper represented a significant milestone in the development of stent technology. Coming only 5 years after his initial call for the development of an “endovascular splint”, Dr Dotter suc- ceeded in significantly pushing the entire field forward and stimulated additional efforts aimed at improving stent technology.

Strengths

This was the first report of successful stent implantation and laid the groundwork for all future efforts.

Weaknesses

While Dr Dotter demonstrated the potential for long-term patency, the small size and limited expandability of the coilspring tubes made them unsuitable for use in humans. As such, the field would essentially remain static until technological advances made self-expanding and balloon- expandable stents possible.

Relevance

Although the technology and techniques developed by Dr Dotter, and described in this paper have no application to modern interventional cardiology, this paper established the feasibility of stent implantation and laid the foundation for further research. Moreover, the scientific ingenuity and intellectual curiosity embodied by Dr Dotter remains a standard for all interventionalists.

Title 2

Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty

Author

Sigwart U, Puel J, Mirkovitch V, Joffre F, Kappenberger L

Reference

N Engl J Med 1987; 316: 701–706

Abstract

Occlusion and restenosis are the most common reasons that transluminal balloon angioplasty may fail to provide long-term benefit. An intravascular mechanical support was therefore developed with the aim of preventing restenosis and sudden closure of diseased arteries after angioplasty. The endoprosthesis consists of a self-expandable stainless-steel mesh that can be implanted nonsur- gically in the coronary or peripheral arteries. Experiments in animals showed complete intimal cov- erage within weeks and no late thrombosis during a follow-up period of up to one year. We performed 10 implantations in 6 patients for iliac or femoral arterial disease; 24 coronary-artery stents were implanted in 19 patients who presented with coronary-artery restenoses (n
17) or abrupt closure (n
4) after transluminal angioplasty or deterioration of coronary-bypass grafts (n
3). We observed three complications in the group with coronary disease. One thrombotic occlusion of a stent resulted in asymptomatic closure, a second acute thrombosis was managed successfully with thrombolysis, and one patient died after bypass surgery for a suspected but unfound occlusion. Follow-up in the patients has continued for nine months without evidence of any further restenoses within the stented segments. Our preliminary experience suggests that this vas- cular endoprosthesis may offer a useful way to prevent occlusion and restenosis after transluminal angioplasty. Long-term follow-up will be required to validate the early success of this procedure.

Summary

In this paper, the investigators describe their experience deploying self-expanding stents in peri- pheral and coronary arteries. The authors used a canine model to demonstrate the feasibility of deploying self-expanding stents in the femoral and coronary arteries of mongrel dogs.

Examination of the stents and arterial segments at 9 months demonstrated endothelialization of stent struts with a smooth neointimal layer. The authors then turned their attention to human sub- jects. In coronary arteries, procedural success was over 90%. In the four patients who received a stent for failed angioplasty, successful delivery of a stent restored coronary blood flow and averted the need for emergency coronary bypass surgery. During follow-up three patients developed stent thromboses (17%) and one patient died (6%). There were no cases of in-stent restenosis, though two patients developed new, symptomatic stenoses at sites remote from the coronary stent.

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Related References

1. Serruys PW, Strauss BH, Beatt KJ, et al. Angiographic follow-up after placement of a self- expanding coronary-artery stent. N Engl J Med 1991; 324: 13–17.

2. Roubin GS, Cannon AD, Agrawal SK, et al. Intracoronary stenting for acute and threatened closure complicating percutaneous transluminal coronary angioplasty. Circulation 1992; 85:

916–927.

Key message

Implantation of stainless steel, self-expanding stents in human coronary arteries can be used to treat acute closure following balloon angioplasty, and may be associated with a lower rate of restenosis.

Why it’s important

By 1987, the potential benefits and limitations of percutaneous balloon angioplasty had largely been identified. Although technical improvements permitted successful dilatation of most lesions, bal- loon angioplasty was limited in the short term by acute closure and in the long term by restenosis.

Other technologies aimed at circumventing these problems included directional atherectomy, rotablation, and laser angioplasty. In this paper, Sigwart and colleagues established the technical feasibility and safety of the placement of intravascular stainless-steel stents in human peripheral and coronary arteries, and established stents as a potentially useful adjunct to balloon angioplasty.

Strengths

This paper was another landmark in the application of stent technology and represented the largest series of patients successfully treated with self-expanding stent implantation.

Weaknesses

As a case series, the investigators have no control group for comparison, and it is likely the majority of cases could have been treated successfully with simple balloon angioplasty. In addition, while starting to identify the periprocedural risks associated with stent implantation, the number of patients was too small and the clinical follow-up was too short to define fully the risks of stent thrombosis and in-stent stenosis.

Relevance

This paper was the first to bring significant attention to the potential of intracoronary-stent implantation. It represents a pivotal moment in the history of interventional cardiology providing evidence that intravascular stents could be used to prevent or treat acute closure and hinting at the possibility of reducing restenosis. Nevertheless as the authors accurately stated, “further studies will determine with greater precision the benefits and risks of this new approach”.

Title 3

A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease

Author

Fischman DL, Leon MB, Baim DS, et al., for the Stent Restenosis Study Investigators

Reference

N Engl J Med 1994; 331: 496–501

Abstract

BACKGROUND: Coronary-stent placement is a new technique in which a balloon-expandable, stainless-steel, slotted tube is implanted at the site of a coronary stenosis. The purpose of this study was to compare the effects of stent placement and standard balloon angioplasty on angio- graphically detected restenosis and clinical outcomes. METHODS: We randomly assigned 410 patients with symptomatic coronary disease to elective placement of a Palmaz–Schatz stent or to standard balloon angioplasty. Coronary angiography was performed at base line, immediately after the procedure, and six months later. RESULTS: The patients who underwent stenting had a higher rate of procedural success than those who underwent standard balloon angioplasty (96.1 percent vs. 89.6 percent, p
0.011), a larger immediate increase in the diameter of the lumen (1.72 0.46 vs. 1.23  0.48 mm, p  0.001), and a larger luminal diameter immediately after the procedure (2.49 0.43 vs. 1.99  0.47 mm, p  0.001). At six months, the patients with stented lesions continued to have a larger luminal diameter (1.74 0.60 vs. 1.56  0.65 mm, p
0.007) and a lower rate of restenosis (31.6 percent vs. 42.1 percent, p
0.046) than those treated with balloon angioplasty. There were no coronary events (death; myocardial infarction; coronary-artery bypass surgery; vessel closure, including stent thrombosis; or repeated angioplasty) in 80.5 per- cent of the patients in the stent group and 76.2 percent of those in the angioplasty group ( p
0.16). Revascularization of the original target lesion because of recurrent myocardial ischemia was performed less frequently in the stent group than in the angioplasty group (10.2 per- cent vs. 15.4 percent, p
0.06). CONCLUSIONS: In selected patients, placement of an intra- coronary stent, as compared with balloon angioplasty, results in an improved rate of procedural success, a lower rate of angiographically detected restenosis, a similar rate of clinical events after six months, and a less frequent need for revascularization of the original coronary lesion.

Summary

To determine the effectiveness of coronary stents to prevent restenosis, investigators random- ized 470 patients to compare a strategy of elective stent implantation with a strategy of balloon angioplasty with bail-out stenting for threatened closure or residual stenosis. Procedural success was significantly higher in the elective stent group with larger luminal diameters. Routine angiog- raphy at 6 months demonstrated a significantly lower rate of restenosis in the elective stent group compared with the balloon angioplasty group (31.6% vs. 42.1%). Revascularization for recurrent ischaemia was lower in the stent group, but there was a non-significant trend towards a higher risk of the combined end point of death, myocardial infarction, and vessel closure.

Citation Count

Related References

1. Serruys PW, de Jaegere P, Kiemeneij F, et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994; 331: 489–495.

2. Erbel R, Haude M, Hopp HW, et al. Coronary-artery stenting compared with balloon angioplasty for restenosis after initial balloon angioplasty. N Engl J Med 1998; 339: 1672–1678.

3. Versaci F, Gaspardone A, Tomai F, et al. A comparison of coronary-artery stenting with angioplasty for isolated stenosis of the proximal left coronary artery. N Engl J Med 1997; 336:

817–822.

4. Buller CE, Vladimir D, Carere RG, et al. Primary stenting versus balloon angioplasty in occluded coronary arteries. Circulation 1999; 100: 236–242.

Key message

The elective use of coronary stents improves procedural success and reduces rates of restenosis, but may be associated with slightly increased risk of major adverse cardiac events.

Why it’s important

Previous studies had defined a role for stents to prevent acute closure consequent to dissection or inadequate balloon angioplasty result. Although there was accumulating evidence that stents might lower the rates of restenosis, there had been no randomized trials comparing elective vs.

bail-out stenting for this indication. In this setting, the STRESS study, in conjunction with the Belgium–Netherlands Stent (BENESTENT) I trial, provided key evidence that stents significantly reduce (but do not eliminate) restenosis. Coronary stents were the first, and still the only, technology shown to decrease restenosis in randomized clinical trials. The STRESS and BENESTENT I studies served as the basis for the Food and Drug Administration’s (FDA’s) approval of elective coronary stenting in the USA, allowed the widespread adoption of stents, and to a large degree relegated other technologies to smaller, niche roles.

Strengths

The STRESS study was a well-designed and implemented randomized multicentre clinical trial.

Along with BENESTENT I, the STRESS investigators set the standard for trials of stents and other interventional devices.

Weaknesses

The trial protocol specified that lesions had to be less than 15 mm, treatable with a single stent, with a reference lumen of at least 3 mm. As such, the investigators excluded the complex lesions associated with the worst outcomes using balloon angioplasty alone, and it was not known if the results of this trial could be extrapolated to more complex stenoses or patients.

Relevance

In conjunction with the BENESTENT trial, the STRESS study laid the groundwork for approval of elective stenting. Additional studies demonstrated similar efficacy in saphenous vein graft stenoses, longer lesions, and for restenosis after balloon angioplasty. Collectively these trials established the use of coronary stents as the present day standard of care.

Title 4

Intracoronary stenting without anticoagulation

accomplished with intravascular ultrasound guidance

Author

Colombo A, Hall P, Nakamura S, et al.

Reference

Circulation 1995; 91: 1676–1688

Abstract

BACKGROUND: The placement of stents in coronary arteries has been shown to reduce restenosis in comparison to balloon angioplasty. However, clinical use of intracoronary stents is impeded by the risk of subacute stent thrombosis and complications associated with the anti- coagulant regimen. To reduce these complications, the hypothesis that systemic anticoagulation is not necessary when adequate stent expansion is achieved was prospectively evaluated on a consecutive series of patients who received intracoronary stents. METHODS AND RESULTS:

From March 1993 to January 1994, 359 patients underwent Palmaz–Schatz coronary stent insertion. After an initial successful angiographic result with20% stenosis by visual estimation had been achieved, intravascular ultrasound imaging was performed. Further balloon dilatation of the stent was guided by observation of the intravascular ultrasound images. All patients with adequate stent expansion confirmed by ultrasound were treated only with antiplatelet therapy (either ticlopidine for 1 month with short-term aspirin for 5 days or only aspirin) after the procedure.

Clinical success (procedure success without early postprocedural events) at 2 months was achieved in 338 patients (94%). With an inflation pressure of 14.9 3.0 atm and a balloon-to- vessel ratio of 1.17 0.19, optimal stent expansion was achieved in 321 of the 334 patients (96%) who underwent intravascular ultrasound evaluation, with these patients receiving only antiplatelet therapy after the procedure. Despite the absence of anticoagulation, there were only two acute stent thromboses (0.6%) and one subacute stent thrombosis (0.3%) at 2-month clinical follow-up.

Follow-up angiography at 3 to 6 months documented two additional occlusions (0.6%) at the stent site. At 6-month clinical follow-up, angiographically documented stent occlusion had occurred in 5 patients (1.6%). At 6-month clinical follow-up, there was a 5.7% incidence of myocardial infarction, a 6.4% rate of coronary bypass surgery, and a 1.9% incidence of death.

Emergency intervention (emergency angioplasty or bailout stent) for a stent thrombosis event was performed in 3 patients (0.8%). The overall event rate was relatively high because of intrapro- cedural complications that occurred in 16 patients (4.5%). Intraprocedural complications, how- ever, decreased to 1% when angiographically appropriately sized balloons were used for final stent dilations. There was one ischemic vascular complication that occurred at the time of the procedure and one ischemic vascular complication that occurred at the time of angiographic follow-up. By 6 months, repeat angioplasty for symptomatic restenosis was performed in 47 patients (13.1%).

CONCLUSIONS: The Palmaz–Schatz stent can be safely inserted in coronary arteries without subsequent anticoagulation provided that stent expansion is adequate and there are no other flow-limiting lesions present. The use of high-pressure final balloon dilatations and confirmation of adequate stent expansion by intravascular ultrasound provide assurance that anticoagulation therapy can be safely omitted. This technique significantly reduces hospital time and vascular complications and has a low stent thrombosis rate.

Summary

The authors present data from 359 patients who had stent implantation guided by intravascu- lar ultrasound. The authors demonstrated that traditional techniques resulted in underdeployed stents that often did not cover the entire lesion. They further showed that high-pressure inflations (14 atm) using balloons sized to the reference lumen were necessary to attain optimal stent expansion. Optimal stent expansion was attained in 321 patients (89.4%), and these patients received only ticlopidine or aspirin with no additional systemic anticoagula- tion. During follow-up of patients with optimal stent expansion, there were only five stent closures (1.6%).

Citation Count

Related References

1. Nath FC, Muller DWM, Ellis SG, et al. Thrombosis of a flexible coil coronary stent: frequency, predictors, and clinical outcomes. J Am Coll Cardiol 1993; 21: 622–627.

2. Karrillon GJ, Morice MC, Benveniste E, et al. Intracoronary stent implantation without ultrasound guidance and with replacement of conventional anticoagulation by antiplatelet therapy. 30-day clinical outcome of the French Multicenter Registry. Circulation 1996; 94:

1519–1527.

3. Leon MB, Baim DS, Popma JJ, et al. A clinical trial comparing three antithrombotic-drug regi- mens after coronary-artery stenting. N Engl J Med 1997; 339: 1665–1671.

4. Schömig A, Neumann F-J, Kastrati A, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996; 334:

1084–1089.

Key message

Optimal stent implantation can be achieved using intravascular ultrasound, appropriately sized stents, and high-pressure balloon inflations. Patients who receive optimal stent implantation do not require prolonged post-procedural systemic anticoagulation and can be safely treated with antiplatelet agents alone.

Why it’s important

Early recognition of the risks of introducing thrombogenic materials into coronary arteries prompted investigators to use intraprocedural heparin, dextran, and thrombolytic agents fol- lowed by prolonged aspirin, dipyridamole, and warfarin. This regimen, however, was associated with significant risk of bleeding and necessitated prolonged hospitalization, both of which greatly increased costs. Furthermore, in spite of these precautions, the incidence of stent thrombosis was as high as 18% in early case series.

These limitations significantly hindered the adoption of coronary stenting into routine clinical practice. Accordingly, the insights provided by Columbo and colleagues represented an important advance by offering both a practical method favouring high-pressure inflations and at the same time uncoupling stent implantation from the need for prolonged systemic anticoagulation.

Strengths

Although not a randomized clinical trial, the low 1.6% incidence of acute and subacute stent thrombosis in the absence of systemic anticoagulation was a remarkable finding that could almost stand on its own merit.

Weaknesses

Once again there is no direct control group for comparison with this series of patients. However, previous studies had demonstrated at least a 3–4% incidence of stent thrombosis, and in this context the low 1.6% rate of stent thrombosis observed by Columbo and colleagues was extremely favourable. In addition, patients were enrolled at a high volume, referral centres, and it was initially unclear whether similar results could be attained in general interventional practice.

Relevance

The insights of Columbo and colleagues completely changed the practice of stent implantation and ushered in the modern era interventional cardiology. Prior to this publication, stents provided an attractive bail-out option in the case of severe dissection and held promise for decreasing restenosis.

Nevertheless the use of stents was limited by the very real and potentially life-threatening risk of acute stent thrombosis, as well as the requirement of prolonged hospitalizations to achieve sys- temic anticoagulation following stent implantation. Their findings led to the Stent Anticoagulation Restenosis Study (STARS) trial in which patients randomized to aspirin plus ticlopidine had a significantly lower risk of stent thrombosis (0.5%) than patients who received aspirin alone (2.9%) or aspirin plus coumadin (2.7%). Thus the work of Columbo and colleagues freed inter- ventionalists from the need for prolonged anticoagulation and spurred the widespread adoption of routine coronary-stent use.

Title 5

Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease

Author

Serruys PW, Unger F, Sousa JE, Jatene A, Bonnier HJRM, Schonberger JPAM, Buller N, Bonser R, van den Brand MJB, van Herwerden LA, Morel M-AM, van Hout BA, for the Arterial Revascularization Therapies Study (ARTS) Group

Reference

N Engl J Med 2001; 344: 1117–1124

Abstract

BACKGROUND: The recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease. METHODS: A total of 1205 patients were randomly assigned to undergo stent implant- ation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year. The costs of hospital resources used were also determined. RESULTS: At one year, there was no significant difference between the two groups in terms of the rates of death, stroke, or myocardial infarction. Among patients who survived without a stroke or a myocardial infarction, 16.8 percent of those in the stenting group underwent a second revascularization, as compared with 3.5 percent of those in the surgery group. The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery ( p 0.001 by the log-rank test). The costs for the initial procedure were $4212 less for patients assigned to stenting than for those assigned to bypass surgery, but this difference was reduced during follow-up because of the increased need for repeated revascularization; after one year, the net difference in favor of stenting was estimated to be $2973 per patient. CONCLUSIONS:

As measured one year after the procedure, coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death, stroke, and myocardial infarction. However, stenting is associated with a greater need for repeated revascularization.

Summary

The authors enrolled 1205 carefully selected patients with multivessel coronary-artery disease and preserved left ventricular function. Patients were then randomized to either percutaneous intervention with routine stenting or coronary-artery bypass surgery. The incidence of all major adverse clinical events at 1 year was higher in the stenting group than the surgery group (26.2% vs.

12.2%). However, the difference was entirely attributable to the need for repeat revascularization for in-stent restenosis, and the incidence of death, stroke, and myocardial infarction were com- parable (9.3% stent vs. 8.8% surgery). Although angina was more frequent in the stent group due to restenosis, overall quality of life did not differ between the two groups. One-year medical costs including initial procedure were $2973 lower in patients randomized to stenting.

Citation Count

Related References

1. The Bypass Angioplasty Revascularization Investigation (BARI) Investigators. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med 1996; 335: 217–225.

2. King III SB, Lembo NJ, Weintraub WS, et al. A randomized trial comparing coronary angioplasty with coronary bypass surgery. Emory Angioplasty versus Surgery Trial (EAST). N Engl J Med 1994; 331: 1044–1050.

3. Versaci F, Gaspardone A, Tomai F, Crea F, Chiariello L, Gioffre PA. A comparison of coronary- artery stenting with angioplasty for isolated stenosis of the proximal left anterior descending coronary artery. N Engl J Med 1997; 336: 817–822.

4. Legrand VMG, Serruys PW, Unger R, et al. Three-year outcome after coronary stenting versus bypass surgery for the treatment of multivessel disease. Circulation 2004; 109: 1114–1120.

5. Stables RH, The SoS Investigators. Coronary artery bypass surgery versus percutaneous coronary intervention with stent implantation in patients with multivessel coronary artery disease (the Stent or Surgery trial): a randomised controlled trial. Lancet 2002; 360: 965–970.

Key message

Among patients with coronary anatomy suitable to either procedure, a strategy of multivessel percutaneous intervention incorporating routine stenting yields similar 1-year incidence of death, stroke, and myocardial infarction compared with coronary-artery bypass surgery. However, patients treated with stenting required repeat revascularization much more often than patients who underwent bypass surgery.

Why it’s important

While it has long been recognized that percutaneous intervention is preferable to coronary bypass surgery in the treatment of single-vessel coronary disease, the optimal method for mul- tivessel disease has been to be a source of controversy for more than two decades. Randomized comparisons of balloon angioplasty vs. coronary-artery bypass surgery suggested these tech- niques were comparable, and that surgery resulted in less residual ischemia when compared with multivessel angioplasty. In addition, the Bypass Angioplasty Revascularization Investigation (BARI) trial raised the possibility of excess mortality associated with multivessel angioplasty. The emergence of routine stent implantation, however, made a new round of trials necessary to reevaluate this question in the stent era.

Strengths

This is the largest randomized trial of routine stenting and coronary-artery bypass surgery. The study was well designed, and investigators managed to maintain excellent adherence to study protocol.

Weaknesses

The 1-year follow-up was too short to provide a true comparison of the relative merits of stenting vs. surgery. For example, a longer follow-up interval may have revealed a tendency towards graft attrition in the surgical group. As in all trials comparing percutaneous coronary interventions

(PCI) and surgery, the stringent clinical and angiographical characteristics required for enrolment greatly limits the generalizability of these results to the larger population of patients with multivessel coronary disease.

Relevance

The results of the Arterial Revascularization Therapies Study (ARTS) trial provides additional evi- dence that among appropriately selected patients with multivessel coronary disease, percu- taneous intervention with routine stenting offers results that are comparable to those of traditional bypass surgery. Nevertheless, the need for repeat revascularization among stent patients in the ARTS trial, as well the higher mortality among patients randomized to stenting in the Stent or Surgery trial leaves unanswered the question of which technique is superior. The emergence of drug-eluting stents further complicates the relative merits of multivessel angio- plasty vs. bypass surgery and makes yet another round of clinical trials necessary.

Title 6

Intracoronary Stenting and Angiographic Results: Strut Thickness Effect on REstenosis Outcome (ISAR-STEREO) Trial

Author

Kastrati A, Mehilli J, Dirschinger J, et al.

Reference

Circulation 2001; 103: 2816–2821

Abstract

BACKGROUND: Increased thrombogenicity and smooth muscle cell proliferative response induced by the metal struts compromise the advantages of coronary stenting. The objective of this randomized, multicenter study was to assess whether a reduced strut thickness of coronary stents is associated with improved follow-up angiographic and clinical results. METHODS AND RESULTS: A total of 651 patients with coronary lesions situated in native vessels2.8 mm in diameter were randomly assigned to receive 1 of 2 commercially available stents of compar- able design but different thickness: 326 patients to the thin-strut stent (strut thickness of 50m) and 325 patients to the thick-strut stent (strut thickness of 140m). The primary end point was the angiographic restenosis (50% diameter stenosis at follow-up angiography). Secondary end points were the incidence of reinterventions due to restenosis-induced ischemia and the combined rate of death and myocardial infarctions at 1 year. The incidence of angiographic restenosis was 15.0% in the thin-strut group and 25.8% in the thick-strut group (relative risk, 0.58; 95% CI, 0.39 to 0.87; p
0.003). Clinical restenosis was also significantly reduced, with a reintervention rate of 8.6% among thin-strut patients and 13.8% among thick-strut patients (relative risk, 0.62; 95% CI, 0.39 to 0.99; p
0.03). No difference was observed in the combined 1-year rate of death and myocardial infarction. CONCLUSIONS: The use of a thinner-strut device is associated with a significant reduction of angiographic and clinical restenosis after coronary artery stenting. These findings may have relevant implications for the currently most widely used percutaneous coronary intervention.

Summary

To determine the effect of strut thickness on the incidence of restenosis, the authors random- ized 651 patients undergoing percutaneous coronary intervention (PCI) to receive either an Advanced Cardiovascular Systems (ACS) RX Multi-Link stent with 50-m thick struts or an ACS Multi-Link RX Duet with 140-m thick struts. Procedural success was high in both groups, but the thin-strut stent was less likely to be delivered successfully (92.6% vs. 96.9%) requiring crossover to the thick-strut stent. During follow-up, patients who received the thin-strut stent were significantly less likely to have angiographical restenosis (15.0% vs. 25.8%) or restenosis requiring target-vessel revascularization at 1 year (8.6% vs. 13.8%).

Citation Count

Related References

1. Rogers C, Edelman ER. Endovascular stent design dictates experimental restenosis and thrombosis. Circulation 1995; 91: 2995–3001.

2. Garasic JM, Edelman ER, Squire JC, et al. Stent and artery geometry determine intimal thickening independent of arterial injury. Circulation 2000; 101: 812–818.

3. Lansky AJ, Roubin GS, O’Shaughnessy CD, et al. Randomized comparison of GR-II stent and Palmaz–Schatz stent for elective treatment of coronary stenoses. Circulation 2000; 102:

1364–1368.

4. Pache J, Kastrati A, Mehilli J, et al. Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO-2) trial. J Am Coll Cardiol 2003; 41:

1283–1288.

Why it’s important

As the use of coronary stents became routine, competition between an expanding number of stent manufacturers led to refinements in stent design. These innovations resulted in lower stent profile, increased visibility, improved deliverability, and decreased strut thickness. Despite these technological innovations, there was relatively little interest in determining whether differences in stent design would translate into clinically important differences in restenosis. The underlying assumption of many clinicians was that once delivered, all stents provided comparable reductions in restenosis. The Food and Drug Administration (FDA) reinforced this assumption by only requiring stent manufacturers to demonstrate comparable 30-day outcomes. The ISAR-STEREO inves- tigators made a significant contribution to the literature when they demonstrated that stent design does impact on restenosis.

Strengths

ISAR-STEREO was a randomized, multicentre clinical trial that was adequately powered to detect clinically meaningful differences in angiographical restenosis. The investigators used stents that had essentially identical design which minimized the chance that the observed differences in outcome were due to factors other than stent strut thickness.

Weaknesses

Interventional cardiologists were not blinded to the stent type. Similarly, though quantitative cor- onary angiography (QCA) analysis was performed by investigators blinded to group assignment, differences in fluoroscopic appearance may have compromised blinding.

Relevance

Although the ISAR-STEREO investigators definitively demonstrated that design impacts outcome, considerations of stent design have taken a backseat to the emergence of drug-eluting stents.

Nevertheless, optimizing patient outcomes after PCI will require combining the best drug with the best stent platform. Accordingly additional innovations in stent design will no doubt play an important role in the future of interventional cardiology.

Title 7

Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction

Author

Stone GW, Grines CL, Cox DA, et al., for the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Investigators

Reference

N Engl J Med 2002; 346: 957–966

Abstract

BACKGROUND: As compared with thrombolytic therapy, primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction reduces the rates of death, reinfarc- tion, and stroke, but recurrent ischemia, restenosis, and reocclusion of the infarct-related artery remain problematic. When used in combination with PTCA, coronary stenting and platelet glyco- protein IIb/IIIa inhibitors may further improve outcomes. METHODS: Using a 2-by-2 factorial design, we randomly assigned 2082 patients with acute myocardial infarction to undergo PTCA alone (518 patients), PTCA plus abciximab therapy (528), stenting alone with the MultiLink stent (512), or stenting plus abciximab therapy (524). RESULTS: Normal flow was restored in the tar- get vessel in 94.5 to 96.9 percent of patients and did not vary according to the reperfusion strat- egy. At six months, the primary end point – a composite of death, reinfarction, disabling stroke, and ischemia-driven revascularization of the target vessel – had occurred in 20.0 percent of patients after PTCA, 16.5 percent after PTCA plus abciximab, 11.5 percent after stenting, and 10.2 percent after stenting plus abciximab ( p 0.001). There were no significant differences among the groups in the rates of death, stroke, or reinfarction; the difference in the incidence of the primary end point was due entirely to differences in the rates of target-vessel revasculariza- tion (ranging from 15.7 percent after PTCA to 5.2 percent after stenting plus abciximab, p 0.001). The rate of angiographically established restenosis was 40.8 percent after PTCA and 22.2 percent after stenting ( p 0.001), and the respective rates of reocclusion of the infarcted-related artery were 11.3 percent and 5.7 percent ( p
0.01), both independent of abciximab use. CONCLUSIONS: At experienced centers, stent implantation (with or without abciximab therapy) should be considered the routine reperfusion strategy.

Summary

Using a 2-by-2 factorial design, the investigators randomized 2082 patients with acute myocar- dial infarction to receive one of the following treatment strategies: balloon angioplasty alone;

angioplasty with routine stent implantation; balloon angioplasty with the glycoprotein IIb/IIIa inhibitor abciximab; or angioplasty with routine stenting and abciximab. Patients were random- ized after diagnostic angiography and before the start of the percutaneous intervention. As expected, patients randomized to receive a stent had larger luminal diameters and less residual stenoses, but this did not correspond to significant differences in epicardial blood flow. At 30 days, patients randomized to receive a stent, abciximab, or both had lower incidences of the composite end point of death, reinfarction, disabling stroke, or target-vessel revascularization.

At 6 months, the need for revascularization among patients who received a stent was roughly half that of patients who had angioplasty alone with or without abciximab. However, there were no significant differences in the occurrence of death, reinfarction, or disabling stroke.

Citation Count

Related References

1. Zjilstra F, de Boer MJ, Hoorntje JC, et al. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993; 328: 680–684.

2. Stone GW, Brodie BR, Griffin JJ, et al. Clinical and angiographic follow-up after primary stenting in acute myocardial infarction: the PAMI Stent Pilot Trial. Circulation 1999; 99:

1548–1554.

3. Stone GW. Stenting in acute myocardial infarction: observational studies and randomized trials.

J Invest Cardiol 1998; 10: 16a–28a.

4. Grines CL, Cox DA, Stone GW, et al. Coronary angioplasty with or without stent implantation for acute myocardial infarction. N Engl J Med 1999; 341: 1949–1956.

5. Cox DA, Stone GW, Grines CL, et al. Outcomes of optimal or “stent-like” balloon angioplasty in acute myocardial infarction: The CADILLAC trial. J Am Coll Cardiol 2003; 42: 971–977.

Key message

When performing primary angioplasty for acute myocardial infarction, a strategy of routine stent implantation, with or without the use of glycoprotein IIb/IIIa inhibitors improves both angio- graphical and clinical outcomes.

Why it’s important

Primary angioplasty has emerged as the treatment of choice for patients experiencing an acute myocardial infarction. A number of clinical trials have shown that, compared with thrombolytic ther- apy, primary angioplasty improves myocardial salvage and increases event-free survival primarily by reducing reinfarction and the need for target-vessel revascularization. Although pilot studies of stent implantation during primary angioplasty were promising, the first large randomized trial investigating the strategy of routine stent implantation suggested that stent use was associated with reductions in epicardial blood flow and increases in mortality. Based on these findings, it was recommended that stents be reserved for the treatment of suboptimal balloon angioplasty results. The Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) investi- gators provided important information regarding the safety and efficacy of routine stent implantation during primary angioplasty when combined with platelet inhibition.

Strengths

The investigators used relatively broad inclusion criteria to enrol patients who were representa- tive of the broader population of patients with acute myocardial infarction and improve the generalizability of the study’s findings. In addition, approximately 90% of patients who were eligible for enrolment after diagnostic angiography were randomized.

Weaknesses

Randomization took place after diagnostic coronary angiography. While it is unlikely that this affected the angioplasty vs. stent analysis, it may have limited the efficacy of abciximab in this setting.

Relevance

The number of hospitals performing primary angioplasty continues to increase. The CADILLAC trial provided strong evidence that the strategy of routine stent implantation provides superior clinical outcomes to patients undergoing primary angioplasty, and establishes this as the cur- rent standard of care. Nevertheless the design of the trial with initiation of IIb/IIIa inhibition in the catheterization laboratory leaves open the question of whether upstream use of IIb/IIIa inhibitors by paramedics or emergency physicians can lead to further improvements in patient outcomes.

Moreover, additional studies will be needed to refine the technique of primary angioplasty and clarify the role of distal protection devices, thrombectomy, and the use of drug-eluting stents in this setting.

Title 8

Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery

Author

Moses JW, Leon MB, Popma JJ, et al., for the SIRIUS Investigators

Reference

N Engl J Med 2003; 349: 1315–1323

Abstract

BACKGROUND: Preliminary reports of studies involving simple coronary lesions indicate that a sirolimus-eluting stent significantly reduces the risk of restenosis after percutaneous coronary revascularization. METHODS: We conducted a randomized, double-blind trial comparing a sirolimus-eluting stent with a standard stent in 1058 patients at 53 centers in the United States who had a newly diagnosed lesion in a native coronary artery. The coronary disease in these patients was complex because of the frequent presence of diabetes (in 26 percent of patients), the high percentage of patients with longer lesions (mean, 14.4 mm), and small vessels (mean, 2.80 mm). The primary end point was failure of the target vessel (a composite of death from cardiac causes, myocardial infarction, and repeated percutaneous or surgical revascularization of the target vessel) within 270 days. RESULTS: The rate of failure of the target vessel was reduced from 21.0 percent with a standard stent to 8.6 percent with a sirolimus-eluting stent ( p 0.001) – a reduction that was driven largely by a decrease in the frequency of the need for revascularization of the target lesion (16.6 percent in the standard-stent group vs. 4.1 percent in the sirolimus-stent group, p 0.001). The frequency of neointimal hyperplasia within the stent was also decreased in the group that received sirolimus-eluting stents, as assessed by both angiography and intravascu- lar ultrasonography. Subgroup analyses revealed a reduction in the rates of angiographic restenosis and target-lesion revascularization in all subgroups examined. CONCLUSIONS: In this randomized clinical trial involving patients with complex coronary lesions, the use of a sirolimus-eluting stent had a consistent treatment effect, reducing the rates of restenosis and associated clinical events in all subgroups analyzed.

Summary

The investigators randomized 1058 patients with significant coronary-artery disease to receive a sirolimus-eluting stent or a standard bare-metal stent. Over follow-up of 270 days, the use of sirolimus-eluting stents was associated with clinically and statistically significant reductions in both in-stent restenosis (3.2% vs. 35.4%) and in-segment restenosis (8.9% vs. 36.3%) com- pared with standard bare-metal stents. Although the rate of restenosis was considerably higher in patients with diabetes (about 18% in the sirolimus-stent group vs. about 51% in the standard- stent group), the absolute benefits associated with sirolimus-eluting stents were preserved.

Failure to cover the entire injured segment was the primary cause of restenosis in patients ran- domized to sirolimus-eluting stents.

Citation Count

Related References

1. Marx SO, Jayaraman T, Go LO, Marks AR. Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells. Circ Res 1995; 76: 412–417.

2. Suzuki T, Kopia G, Hayashi S, et al. Stent-based delivery of sirolimus reduces neointimal for- mation in a porcine coronary model. Circulation 2001; 104: 1188–1193.

3. Sousa JE, Costa MA, Abizaid A, et al. Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: a quantitative coronary angiography and three-dimensional intravascular ultrasound study. Circulation 2001; 103: 192–195.

4. Morice M-C, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002; 346: 1773–1780.

5. Park S-J, Shim WH, Ho DS, et al. A paclitaxel-eluting stent for the prevention of coronary restenosis. N Engl J Med 2003; 348: 1537–1545.

Key message

Sirolimus-eluting stents significantly reduced restenosis and the need for target-vessel revascu- larization. There was no subgroup who did not benefit from use of sirolimus-eluting stents.

Why it’s important

Since the original reports of complete suppression of neointimal proliferation by both oral and stent-delivered sirolimus, clinicians have eagerly awaited the arrival of drug-coated stents to achieve the ultimate goal of interventional cardiology – safe and effective coronary intervention with no risk of restenosis. These expectations were raised even further by the RAVEL trial in which sirolimus-eluting stents were associated with no restenoses and no repeat interventions. In this environment, the SIRIUS trial played an important role by confirming the promise of sirolimus- eluting stents and serving as the pivotal trial for Food and Drug Administration (FDA) approval in the USA.

Strengths

Another well-designed clinical trial, the SIRIUS trial, provided convincing evidence that sirolimus-eluting stents significantly reduces angiographical restenosis and prevents recurrent ischaemia.

Weaknesses

A number of high-risk lesion subtypes such as total occlusions, long segments of disease, in-stent stenosis, and bifurcation lesions were excluded from the SIRIUS trial. The efficacy of drug-elut- ing stents in these lesion subtypes are being looked at in ongoing trials. Although the authors did not formally test for an interaction between insulin requiring diabetes and efficacy of sirolimus- eluting stents, the relatively high rate of in-segment restenosis in this subgroup may be a cause for concern. Finally, the authors provide no information regarding the cost-effectiveness of sirolimus-eluting stents. Accordingly it is not known whether the incremental costs of drug-eluting stents, which cost more than three times the bare-metal stents, are offset by the decreased expenses attributable to lower rates of repeat revascularization.

Relevance

Since their introduction, drug-eluting stents have rapidly become the standard of care in both the USA and abroad. The SIRIUS trials, in combination with the results from RAVEL and TAXUS have demonstrated consistent reductions in restenosis. If drug-eluting stents prove similarly effi- cacious in all lesion subtypes, they will allow interventional cardiologists to approach more complex lesions and greatly expand the pool of patients who will benefit from percutaneous intervention.

Title 9

Stenting of unprotected left main coronary artery stenoses:

immediate and late outcomes

Author

Park S-J, Park S-W, Hong M-K, et al.

Reference

J Am Coll Cardiol 1998; 31: 37–42

Abstract

OBJECTIVES: We examined the immediate and long-term outcomes after stenting of unpro- tected left main coronary artery (LMCA) stenoses in patients with normal left ventricular (LV) function. BACKGROUND: Left main coronary artery disease is regarded as an absolute con- traindication for coronary angioplasty. Recently, several reports on protected or unprotected LMCA stenting, or both, suggested the possibility of percutaneous intervention for this prohibited area. METHODS: Forty-two consecutive patients with unprotected LMCA stenoses and normal LV function were treated with stents. The post-stent antithrombotic regimens were aspirin and ticlopidine; 14 patients also received warfarin. Patients were followed very closely with monthly telephone interviews and follow-up angiography at 6 months. RESULTS: The procedural success rate was 100%, with no episodes of subacute thrombosis regardless of anticoagulation regimen.

Six-month follow-up angiography was performed in 32 of 34 eligible patients. Angiographic restenosis occurred in seven patients (22%, 95% confidence interval 7% to 37%); five patients subsequently underwent elective coronary artery bypass graft surgery (CABG), and two patients were treated with rotational atherectomy plus adjunct balloon angioplasty. The only death occurred 2 days after elective CABG for treatment of in-stent restenosis. The other patients (without angiographic follow-up) remain asymptomatic. CONCLUSIONS: Stenting of unprotected LMCA stenoses may be a safe and effective alternative to CABG in carefully selected patients with normal LV function. Further studies in larger patient populations are needed to assess late outcome.

Summary

The authors provide characteristics and clinical outcomes of 42 patients with preserved left ven- tricular function who underwent stenting of an isolated, unprotected left main stenosis. All but one patient were thought to be good candidates for coronary-artery bypass surgery but strongly preferred a percutaneous intervention. Stents were used electively in 38 patients and as bail-out therapy in four patients. Procedural success was 100% with no significant peripro- cedural complications and no stent thrombosis. Quantitative coronary angiography (QCA) revealed an increase in minimal luminal diameter from 1.1 mm to 4.2 mm. During follow-up, seven patients (17%) had symptomatic restenosis less than 2 months after the procedure.

Among the 32 patients who underwent angiography at 6 months, restenosis occurred in seven patients. The only death occurred in a patient with in-stent stenosis who was referred for elect- ive coronary bypass surgery.

Citation Count

Related References

1. O’Keefe Jr JH, Hartzler GO, Rutherford BD, et al. Left main coronary angioplasty: early and late results of 127 acute and elective procedures. Am J Cardiol 1989; 64: 144–147.

2. Ellis SG, Tamai H, Nobuyoshi M, et al. Contemporary percutaneous treatment of unprotected left main coronary stenoses: initial results from a multicenter registry analysis 1994–1996.

Circulation 1997; 96: 3867–3872.

3. Silvestri M, Barragan P, Sainsous J, et al. Unprotected left main coronary artery stenting:

immediate and medium-term outcomes of 140 elective procedures. J Am Coll Cardiol 2000;

35: 1543–1550.

4. Park SJ, Park SW, Hong MK, et al. Long-term (three-year) outcomes after stenting of unpro- tected left main coronary artery stenosis in patients with normal left ventricular function. Am J Cardiol 2003; 91: 12–16.

Key message

In carefully selected, low-risk patients with isolated stenosis of the left main coronary artery, per- cutaneous intervention with routine stenting may offer an alternative to coronary bypass surgery.

However, patients are at significant risk of symptomatic restenosis and require close monitoring and routine angiography to identify recurrent ischaemia.

Why it’s important

Left main lesions present a unique challenge to the interventional cardiologist. In the era of balloon angioplasty, patient outcomes were disappointing with high rates of symptomatic restenosis and the spectre of catastrophic acute closure. The arrival of coronary stents improved procedural success rates, but did not eliminate the risk of restenosis or stent thrombosis. In this setting, this case series provided an important first glimpse at both the promise and pitfalls of left main stenting.

While initial procedural success was high, the 17% rate of restenosis presenting as unstable angina would give clinicians pause before adopting left main stenting as part of their interventional practice.

Strengths

There are two major strengths to this study. First, stents were implanted in all patients, which was not the case in other registries of left main stenting. Second, the authors almost exclusively enrolled patients who were also candidates for bypass surgery. Accordingly, patients were more similar to patients in clinical practice who are referred for coronary bypass surgery than what has been reported in other registries.

Weaknesses

This case series is far too small to determine the true risks and outcomes associated with stent implantation in unprotected left main stenosis. Although the authors excelled at identifying appropriate patients as evidenced by the high rate of procedural success, it may be difficult to replicate their decision-making process based on the description provided.

Relevance

For patients with significant stenosis of the left main artery, coronary bypass surgery offers a proven therapy shown to provide a survival advantage over medical therapy. In part due to the risks

identified by Park and colleagues, the interventional community has remained appropriately reluctant to perform percutaneous interventions on left main disease in the absence of a relative or absolute contraindication to surgery. Nevertheless, pharmacological advances and the low restenosis rates achieved with drug-eluting stents may allow left main stenting to offer a safe and efficacious alternative to coronary-artery bypass surgery. At present, however, stenting of the left main remains largely a therapy of last resort, one usually employed in the setting of a car- diac emergency, severe co-morbid disease, or a patient’s refusal to consider bypass surgery.