Clinical review

Intracoronary stents

Manish M Gandhi, senior registrar in cardiology,  Keith D Dawkins, consultant cardiologist. 

Wessex Cardiothoracic Centre, Southampton University Hospital, Southampton SO16 6YD

Correspondence to: Dr Gandhi

During the past five years there has been a sharp increase in the use of intracoronary stents as an adjunct to percutaneous transluminal coronary angioplasty (PTCA) for the revascularisation of patients with angina. In 1996 stents were used in half (mean 46%, range 15-99%) of the 20 500 PTCA procedures undertaken in the United Kingdom, representing a fivefold increase since 1994 (HH Gray, personal communication).

Stents were developed to improve clinical outcome after PTCA. In selected patients, PTCA is as effective as bypass surgery,¹ and more effective than medical treatment,² in relieving angina. The early benefit of PTCA over medical treatment particularly applies to patients with severe angina and single vessel coronary artery disease at baseline. This benefit, however, diminishes during long term follow up and in patients with multivessel coronary artery disease, partly because repeat revascularisation is required for restenosis. ^{3 4} In the early days after the first PTCA was performed in 1977, abrupt periprocedural closure of vessels and late angiographic restenosis were apparent.⁵ In an attempt to overcome these limitations, the first report of 24 coronary stents deployed in 19 patients was published 10 years later.⁶

View larger version (112K): [in this window] [in a new window]   Fig 1.   Balloon catheter (a), and close up of tip with balloon mounted coronary stent (b)

Stents are flexible endovascular prostheses made from stainless steel alloys. They are designed as either metallic coils or slotted tubes.⁷ Most stents are expandable by balloon, and some are self expanding. The stent is mounted on a balloon catheter and, with the aid of fluoroscopic screening and radiopaque markers, is positioned across the stenotic lesion, which has usually been predilated with a balloon. Inflation of the balloon results in expansion and deployment of the stent circumferentially in apposition to the endothelial surface of the coronary artery (figs 1 to 3). Available stents range from 2.5 mm to 6 mm in diameter and from 8 mm to 50 mm in length.

View larger version (46K): [in this window] [in a new window]   Fig 2.   Stent deployment. Accessing the femoral artery, a guide catheter is selectively engaged into the coronary artery ostium (left). The stenotic lesion is crossed with a guide wire (a), and the stent positioned across the predilated lesion and deployed by inflation of the balloon (b) resulting in an increase in luminal diameter of the vessel and improved blood flow (c)

View larger version (120K): [in this window] [in a new window]   Fig 3.   Severe stenosis in a coronary artery (top), and angiographic appearance (bottom) after stent deployment

	Methods

Top Methods Improved outcome Indications for stenting Stent thrombosis and... Long term follow up Stents in acute myocardial... Cost implications Future developments References

This article discusses the rapid emergence of intracoronary stent deployment as the "norm" in percutaneous coronary revascularisation. It is based on key randomised controlled trials or observational studies, published in peer reviewed journals, which have had an impact on changing coronary stenting practice during the past five years. As many aspects of best stenting practice continue to evolve rapidly, this article is based on the most recent literature combined with personal experience.

	Improved outcome

Top Methods Improved outcome Indications for stenting Stent thrombosis and... Long term follow up Stents in acute myocardial... Cost implications Future developments References

Two important studies published in 1994 resulted in an exponential increase in the use of intracoronary stents worldwide. The Benestent study⁸ and the stent restenosis study (STRESS⁹) were prospective randomised controlled trials that compared conventional coronary balloon angioplasty with stent implantation in patients with stable and unstable angina who had a single, de novo, focal stenosis in a large (>3 mm diameter) native coronary artery. After a six month follow up, the primary clinical end point in the Benestent studya composite of death, myocardial infarction, cerebrovascular accident, coronary artery bypass grafting, or repeat PTCAwas reached by significantly fewer patients in the stent group than in the PTCA group; 20% versus 30% respectively (relative risk 0.68, 95% confidence interval 0.5 to 0.92).⁸ In the stent restenosis study, the primary end point of angiographic restenosis at six months was significantly reduced in the stent group compared with the PTCA group32% versus 42% (P=0.046) respectively.⁹ In both studies, target lesion revascularisation was the more favourable clinical outcome in the stent groupthat is, the need for a second intervention involving the original coronary lesion.

Smaller trials in selected subgroups showed that patients who received stents for isolated stenosis of the proximal left anterior descending artery had less angina after one year.¹⁰ Less impressive differences were found in patients with bypass graft disease (table).¹¹

No significant differences have been reported between stenting and other forms of coronary revascularisation or medical treatment for death and myocardial infarction.

	Indications for stenting

Top Methods Improved outcome Indications for stenting Stent thrombosis and... Long term follow up Stents in acute myocardial... Cost implications Future developments References

Cardiologists rely almost exclusively on angiographic criteria for selecting patients for intracoronary stenting (fig 4). Clinical profiles and the results of non-invasive investigations can identify patients for cardiac catheterisation and possibly revascularisation but do not predict the most suitable treatment.

View larger version (51K): [in this window] [in a new window]   Fig 4.   Angiographic criteria used to select patients for deployment of intracoronary stents

	Stent thrombosis and antiplatelet treatment

Top Methods Improved outcome Indications for stenting Stent thrombosis and... Long term follow up Stents in acute myocardial... Cost implications Future developments References

Subacute stent thrombosis occurs in 0.8-3% of patients, usually within 7-10 days of the procedure, and results in occlusion of the stented vessel with platelet rich thrombus and associated myocardial infarction or death. To prevent this, the earlier use of aspirin, heparin, dipyridamole, and dextran was followed by the addition of warfarin. This was associated with a stent thrombosis rate of about 3.5% in clinical trials. ^{8 9}

During the past three years warfarin has been abandoned, as it is now recognised that antiplatelet treatment rather than anticoagulant treatment is the key to minimising the risk of subacute stent thrombosis. The synergistic combination of aspirin and ticlopidineticlopidine is an inhibitor of adenosine diphosphate induced platelet activationwas associated with a stent occlusion rate of only 0.8% compared with 5.4% with anticoagulation treatment.¹² These results have been confirmed elsewhere.¹³ Neutropenia (severe in 0.8% of patients), rash, and diarrhoea are side effects associated with ticlopidine, and necessitate regular monitoring of the white cell count. It is likely that ticlopidine will be replaced by clopidogrel, a less expensive but structurally similar drug reported to have fewer side effects.

In patients undergoing elective stenting, complications associated with the procedurein particular Q wave and non-Q wave myocardial infarctionare further reduced by intravenous abciximab.¹⁴ This is a fragment of monoclonal antibody that inhibits the platelet glycoprotein IIb/IIIa receptor involved in the final common pathway of platelet aggregation. At £840 per patient dose, abciximab is expensive and costs as much as or more than a stent; its cost effectiveness therefore needs to be carefully assessed when long term follow up data become available.

After discharge
Patients are advised to avoid driving for one week after coronary stenting, and to quit cigarette smoking permanently. We aim for a total fasting cholesterol concentration of <5.2 mmol/l. Bleeding with haematoma at the puncture site or a false femoral artery aneurysm can develop during the first few days after the procedure in 1.5-2.5% of patients. These patients require re-referral to the cardiologist for possible transfusion or surgical repair.

	Long term follow up

Top Methods Improved outcome Indications for stenting Stent thrombosis and... Long term follow up Stents in acute myocardial... Cost implications Future developments References

The beneficial effect of stenting over PTCA alone is maintained at one year. ^{15 16} Trial patients do not necessarily reflect clinical practice, however, and outcome in more heterogenous patients may be less favourable.¹⁷ In observational studies, the proportion of patients requiring additional revascularisation up to two years after stenting varied between 17% and 39%.^18-20 These data, based on retrospective cohorts, no longer apply because patients were recruited in the early days of stenting when the indications were predominantly bailout situations, restenotic lesions, or graft disease, and warfarin was used routinelyfactors now known to be associated with a worse clinical outcome. Long term outcome data in the current era of stenting with antiplatelet treatment are awaited.

	Stents in acute myocardial infarction

Top Methods Improved outcome Indications for stenting Stent thrombosis and... Long term follow up Stents in acute myocardial... Cost implications Future developments References

A randomised study that compared PTCA with thrombolysis in 395 patients with acute myocardial infarction reported a 60% reduction in hospital mortality and a 49% reduction in the composite end point of reinfarction and death in favour of PTCA after a six month follow up.²¹ These findings were not confirmed in a district hospital setting²² and generated an intense debate about the role of immediate or primary coronary angioplasty instead of thrombolytic treatment for acute myocardial infarction.²³ The discrepant results underline important issues in deciding the applicability of trial data, patient selection being the most critical. In the primary angioplasty in myocardial infarction (PAMI) trial, 395 patients with acute myocardial infarction were enrolled from 12 centres over a 23 month period. This gave a trial recruitment rate of 1.4 patients per centre per month or less than one patient per centre per month to the PTCA arm. This implies that, for whatever reason, more than 90% of patients presenting with acute myocardial infarction to these centres must have been excluded from the trial, severely limiting the extrapolation of results to the generality of patients presenting with acute myocardial infarction.

Unless a register of all possible patients is maintained, similar limitations will restrict the meaningful extrapolation of results from several small trials currently assessing the value of primary stenting in acute myocardial infarction.²⁴

	Cost implications

Top Methods Improved outcome Indications for stenting Stent thrombosis and... Long term follow up Stents in acute myocardial... Cost implications Future developments References

Purchasers of health care must be aware that lack of conclusive cost to benefit data for coronary stenting is not synonymous with lack of clinical efficacy. Cost effectiveness analysis of life years gained and quality adjusted life years gained require follow up over years. Such long term follow up is currently unavailable and indeed unlikely to be available because of the very rapid evolution of standard practice that outdates trials often before they are published.

	Future developments

Top Methods Improved outcome Indications for stenting Stent thrombosis and... Long term follow up Stents in acute myocardial... Cost implications Future developments References

The massive growth in use of intracoronary stents is mirrored by important advances in the reduction of within stent restenosis. Restenosis after coronary intervention is thought to result from the dual mechanism of recoil and geometric remodelling of the vessel, as well as from a proliferative response to injuryintimal hyperplasia being caused by smooth muscle cell migration and matrix production. In contrast to PTCA alone, the scaffolding effect of stent deployment may diminish recoil and remodelling but is thought to increase neointimal hyperplasia. Attempts to reduce within stent restenosis include evaluation of intracoronary radiotherapy using catheter based  radiation,²⁵ radioactive stents, the delivery of recombinant vascular endothelial growth factor with a balloon catheter to speed endothelialisation of a stent,²⁶ gene therapy, and local drug delivery.²⁷

In clinical practice, intracoronary stenting has become an indispensable tool for cardiologists, producing in most cases a far superior angiographic result than that of PTCA alone. But to what extent does responding to the oculostenotic reflexthe urge to intervene when an angiographically severe stenosis is visualisedand resultant satisfaction for the interventionist translate to better clinical outcome? Multiple stents, for example, are widely used, but in certain subsets of patient may be associated with more frequent subacute thrombosis.²⁸ Similar uncertainties of outcome benefit exist for patients with chronic total occlusions, long lesions, bifurcation lesions, diffuse non-discrete stenoses, and diabetes. Among the most eagerly awaited clinical trials will be the comparison of coronary stenting with bypass graft surgery in patients with multivessel disease. At least two such randomised clinical trials, the arterial revascularisation therapy study (ARTS) and the stent or surgery (SOS) study, are currently under way.

As we go into the new millennium, however, it seems likely that treatments other than metallic coronary implants will ultimately emerge to provide a more long term and widely applicable solution for symptomatic coronary artery disease.

	Acknowledgments

Funding: Wessex Cardiothoracic Centre.

Competing interests: None declared.

website extra: An extended version of this article appears on the BMJ's website www.bmj.com

	References

Top Methods Improved outcome Indications for stenting Stent thrombosis and... Long term follow up Stents in acute myocardial... Cost implications Future developments References

1. Pocock SJ, Henderson RA, Rickards AF, Hampton JR, King III SB, Hamm CW, et al. Meta-analysis of randomised trials comparing coronary angioplasty with bypass surgery. Lancet 1995; 346: 1184-1189[Medline].
2. Parisi AF, Folland ED, Hartigan P, on behalf of the Veterans Affairs Angioplasty Compared to Medicine study investigators. A comparison of angioplasty with medical therapy in the treatment of single-vessel coronary artery disease. N Engl J Med 1992; 326: 10-16[Abstract].
3. Folland ED, Hartigan PM, Parisi AF. Percutaneous transluminal coronary angioplasty versus medical therapy for stable angina pectoris. J Am Coll Cardiol 1997; 29: 1505-1511[Abstract].
4. Participants in the Randomised Intervention Treatment of Angina (RITA-2) trial. Coronary angioplasty versus medical therapy for angina: the second randomised intervention treatment of angina (RITA-2) trial. Lancet 1997; 350: 461-468[Medline].
5. Gruentzig AR, Senning A, Siegenthaler WE. Non-operative dilatation of coronary artery stenosis: percutaneous transluminal coronary angioplasty. N Engl J Med 1979; 301: 61-68[Abstract].
6. Sigwart U, Puel J, Mirkovitch V, Joffre F, Kappenberger L. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N Engl J Med 1987; 316: 701-706[Abstract].
7. Serruys PW. Handbook of coronary stents. London: Martin Dunitz , 1997.
8. Serruys PW, Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, 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[Abstract/Free Full Text].
9. Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, et al. A randomised comparison of coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994; 331: 496-501[Abstract/Free Full Text].
10. 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[Abstract/Free Full Text].
11. Savage MP, Douglas JS, Fischman DL, Pepine CJ, King III SB, Werner JA, et al. Stent placement compared with balloon angioplasty for obstructed coronary bypass grafts. N Engl J Med 1997; 337: 740-747[Abstract/Free Full Text].
12. Schomig A, Neumann FJ, Kastrati A, Schuhlen H, Blasini R, Hadamitzky M, et al. A randomised comparison of antiplatelet and anticoagulent therapy after the placement of coronary artery stents. N Engl J Med 1996; 334: 1084-1089[Abstract/Free Full Text].
13. Leon M, Baim D, Popma J, Gordon P, Cutlip D, Ho K, et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. N Engl J Med 1998; 339: 1665-1671[Abstract/Free Full Text].
14. The EPISTENT investigators. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein IIb/IIIa blockade. Lancet 1998; 352: 87-92[Medline].
15. Serruys PW, van Hout B, Bonnier H, Legrand V, Garcia E, Macaya C, et al, for the Benestent Study Group. Randomised comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II). Lancet 1998; 352: 673-681[Medline].
16. Macaya C, Serruys PW, Ruygrok P, Suryapranata H, Mast G, Klugmann S, et al. Continued benefit of coronary stenting versus balloon angioplasty: one year clinical follow-up of Benestent trial. J Am Coll Cardiol 1996; 27: 255-261[Abstract].
17. Schwartz L, Blew B, Bui S. Intracoronary stent placement for coronary artery disease (letter). Lancet 1997; 350: 113-114[Medline].
18. Kimura T, Yokoi H, Nakagawa Y, Tamura T, Kaburagi S, Sawada Y, et al. Three-year follow-up after implantation of metallic coronary artery stents. N Engl J Med 1996; 334: 561-566[Abstract/Free Full Text].
19. Klugherz B, De Angelo D, Herrmann H, Hirshfeld J, Kolansky D. Three-year clinical follow-up after Palmaz-Schatz stenting. J Am Coll Cardiol 1996; 27: 1185-1191[Abstract].
20. Moussa I, Reimers B, Moses J, Di Mario C, Di Francesco L, Ferraro M, et al. Long term angiographic and clinical outcome of patients undergoing multivessel coronary stenting. Circulation 1997; 96: 3873-3879[Abstract/Free Full Text].
21. Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O'Keefe J, et al, for the PAMI study group. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993; 328: 673-679[Abstract/Free Full Text].
22. Every NR, Parsons LS, Hlatky M, Martin JS, Weaver WD, for the Myocardial Infarction Triage and Intervention Investigators. A comparison of thrombolytic therapy with primary coronary angioplasty for acute myocardial infarction. N Engl J Med 1996; 335: 1253-1260[Abstract/Free Full Text].
23. Lange RA, Hillis LD, Grines CL. Should thrombolysis or primary angioplasty be the treatment of choice for acute myocardial infarction? N Engl J Med 1996; 335: 1311-1317[Free Full Text].
24. Stone GW. Stenting in acute myocardial infarction: observational studies and randomized trials - 1998. J Inv Cardiol 1998; 10(suppl A): 16-26A.
25. Teirstein PS, Massullo V, Jani S, Popma JJ, Mintz GS, Russo RJ, et al. Catheter-based radiotherapy to inhibit restenosis after coronary stenting. N Engl J Med 1997; 336: 1697-1703[Abstract/Free Full Text].
26. Schneider D, Dichek DA. Intravascular stent endothelialisation, a goal worth pursuing? Circulation 1997; 95: 308-310[Free Full Text].
27. Bailey SR. Local drug delivery: current applications. Prog Cardiovasc Dis 1997; 40: 183-204[Medline].
28. Moussa I, Di Mario C, Reimers B, Akiyama T, Tobis J, Colombo A. Subacute stent thrombosis in the era of intravascular ultrasound-guided coronary stenting without anticoagulation: frequency, predictors and clinical outcome. J Am Coll Cardiol 1997; 29: 6-12[Abstract].