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ARE STENTS BEING OVER USED?

Pradeep K Shetty
Senior Consultant Cardiologist, ST John’s Hospital, Bangalore.

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Coronary angioplasty has replaced coronary artery bypass graft surgery as the prime mode of revascularisation in recent years. Percutaneous coronary angioplasty (PTCA) has undergone a dramatic transformation to include mechanical devices and endoprosthesis. In the US, stenting amounts to over 60% of percutaneous revascularisation procedures. [1] In the last couple of years the proportion of stenting is probably higher in India, exceeding 75%. In the US in 1998 alone, over half a million patients have received stents at an average of 1.7 stents per patient. [1]

From the time of the first PTCA was performed by Dr. Gruntzig, two problems have continued to nag the interventionist. Acute vessel closure and restenosis within the first six months. To over come these limitations several techniques were tried of which intra coronary stenting has proved very useful. Stenting was initially indicated specifically for acute vessel closure or threatened closure. Aggressive anticoagulation as practised initially has been abandoned. Antiplatelet drugs Aspirin and Ticlopidine and high pressure stent deployment reduced the incidence of acute stent thrombosis, resulting in shorter hospital stay, and reduced bleeding complications with resultant cost saving. However stents ability to reduce the incidence of restenosis is still controversial. [2]

Are stents being overused? This is a difficult question to answer and even more difficult to prove either way. There has been a phenomenal growth in the usage of stents in the last four years. Is it due to the interventionist’s conviction or does it reflect a response to angiographic gratification? i.e., the image of a large smooth arterial lumen as mused by Eric Topol, [1] in his editorial which he aptly calls the "oculo stentotic reflex".

The oft quoted trials regarding clinical benefits of stenting as compared to balloon angioplasty have highlighted a lower need of target vessel revascularisation. However the risk of death or myocardial infarction is higher in stented patients as shown in a recent large clinical trial and this risk was averted by the use of GP IIb/IIIa receptor blockade. [3]

HISTORICAL BACKGROUND

When stents were first used in 1986 the indications were acute vessel closure during coronary angioplasty (Bailout), treatment of restenosis, and narrowing of saphenous vein grafts. In 1994 the Benestent and Stress trials showed superiority of stenting over PTCA in relation to restenosis. [4, 5] The advent of ticlopidine and later GP IIb/IIIa receptor blocker "abciximab" have rendered stenting safe in relation to stent thrombosis which at present is a rare complication. Plain balloon angioplasty is more time consuming, has inferior angiographic result, and has a higher rate of reported restenosis which have all made stenting extremely popular. Based on the above two trials, in May 1994 the FDA approved the Palmaz Schatz stent for elective coronary placement in selected group of patients to prevent restenosis following angioplasty.

However at this point of time there are several caveats in elective stenting.

1. Long term results are still unknown.
2. At one year there is some reduction in the benefit of stenting over balloon angioplasty
   raising the question that stenting only delays rather than prevent restenosis.
   
3. There are few data on the potential late migration of the stent, metal fatigue, endarteritis,
   and other late complications of metallic endoprosthesis that are possible. [6]
4. There is a definite risk of sub acute stent thrombosis (though reduced due to abciximab
   usage) which can result in death or Myocardial infarction.
5. Stents are expensive and result in longer hospital stay.
6. The patient groups in Benestent and Stress trials may not be representative of larger population of patients who may need stenting.
7. The patients who are likely to benefit most, i.e. those who are likely to develop restenosis
   after PTCA, have not yet been identified and studied in a randomised trial.
8. There is more restenotic tissue as a result of greater luminal diameter produced by
   stenting, thereby higher intimal hyperplasia.
9. Stents result in higher degree of neointimal formation and are difficult to use in some situations as in bifurcation stenosis.
10. Stents are responsible for the new, difficult to treat entity called "instent restenosis".
11. Stents are a problem to the operating surgeon while operating in patients who ultimately
    have to go through coronary artery bypass graft surgery.
12. Stent endarteritis is a dreaded complication and mostly fatal.
13. The complications of vessel perforation and rupture are mainly complications of high pressure stent deployment.
14. Improved efficacy of plain ordinary balloon angioplasty are reflected in the results of the controlled arms of three recent major clinical trials namely BOAT, BENESTENT II, and EPILOG, each showing a cross over rate of only 14% to stenting in its patients randomised
    to receive balloon angioplasty.
15. The overall rate of target vessel revascularisation in these three trials for balloon
    angioplasty was only 17.5%.

These results provide evidence that limited use of provisional stenting for sub optimal results may be very effective. This also reveals that over 80% of patients who received plain balloon angioplasty remained free from clinical restenosis, questioning the strategy of universal stenting. What is to be seen is how these two approaches can be best used together to optimise clinical results and reduce costs. At present universal stent placement has to be undertaken in 100 patients to benefit a meagre 5 or 6 patients. [2]

However, the Cardiologist may be seduced by the angiographic appearance of the vessel immediately after stenting and thereby overusing the stent. Discriminate use of stents can be justified in patients who are at high risk of restenosis, with large target vessel dimension and new focal lesion of less then 15 mm in length, and patients who have significant dissection following balloon angioplasty.

Highlighting this fact is that in the BENESTENT I trial, among the 90 patients who received angioplasty alone and were left with less than 30% residual stenosis, restenosis rate of 16% at one year and event free survival of 77% are nearly identical to the results of those who received the stents. The safety of plain balloon angioplasty is further enhanced by selective use of intravascular ultrasound (IVUS) and use of abciximab, which can also help to identify the patients who need stenting. In the CLOUT7 trial, optimal use of balloon after IVUS guidance, increased the vessel MLD from the mean of 1.95 + 0.49 to 2.21 + 0.47 using an average balloon artery ratio of 1.3 : 1.

Results of OCBAS (Optimal coronary balloon angioplasty versus stent study, [8] 116 patients withgood immediate result after POBA (Plain ordinary balloon angioplasty) randomised to either elective stenting or stenting for lesions only showing early loss of more than 0.3 mm within 30 minutes of balloon dilatation, only 13.5% patients in the angio plasty group required stenting and clinical and angiographic follow up showed no significant differences between the two groups in restenosis, target vessel revascularisation and freedom from major events.

In the BENESTENT II [9] study heparin coated stents were compared with plain ordinary balloon angioplasty in a selected group of patients. At six months a primary clinical end point occurred in 12.8% in stent group compared to 19.3% in the POBA group. Event free survival at 12 months was higher in the stent group (89%) vs 79% in the POBA group but at an additional cost of over 1,000 US Dollars per patient. However the hard end points of death (1% vs 1%) QMI (1.7% vs 1.9%) CABG (2.2% vs 2.4%) for POBA vs stenting were no different at 12 months.

The BENESTENT II revealed that the stenting was mainly beneficial to LAD lesions. Even more significant was the fact that the clinical outcome at one year for stent like result of POBA was similar to that of primary stented patient. [10]

Incidence of clinical events during follow up in 3 recent trials stent vs balloon
Event	Benestent II [9] 12 month follow up (%)	Restenosis stent [12] study 6 month follow up (%)	PAMI [13] 30 days follow up (%)
Death	1.0 vs 1.0	1.1 vs 1.1	0.8 vs 0
QMI	1.9 vs 1.7	2.8 vs 0.6	1.7 vs 0
Non QMI	1.5 vs 2.9	1.7 vs 0.6	—
CABG	1.9 vs 1.5	2.2 vs 0.6	—
TVR	11.9 vs 17.8	10.3 vs 26.0	5.0 vs 8.3

Clinical events in 3 different clinical trials involving native denovo lesions, restenotic lesion and primary angioplasty patients show no significant change in death, QMI, Non QMI and CABG. Only difference is in the rate of target vessel revascularisation (TVR).

Long term results and success rates after standard balloon angioplasty have improved significantly due to enhanced operator experience and improved equipment. It is also benefited by the availability of stents for bailout and backup situations, resulting in more aggressive balloon dilatation.

Mechanically stents scaffold the vessel wall, tacks up dissection, resulting in immediate vessel patency and flow. These endovascular devices stretch the vessel wall causing injury resulting in neointimal proliferation. This is expected to be counter balanced to some extent by the higher gain in luminal dimension.

In the US stenting procedure costs approximately 1,000 US dollars in excess per patient. In the US the stent production is a multi billion industry and it is presumed that it has a profit margin of over 85-90% [1] However fortunately in India the costs have come down quite remarkably in the last year or so, yet the additional cost per patient would be around Rs. 30,000/- on an average for every stent used.

Even in the 1960s the accuracy and reproducibility of coronary angiography was questioned. [11] Recently investigators have focussed on discordance between angiographic lesion and physiological effects of coronary stenosis. The important feature which stimulated the growth of stenting is improvement in the coronary luminogram. Stenting adds a 30% greater improvement to the initial lumen calibre but there is definitely an attrition over time. This angiographic gratification persists at 6 months follow up, resulting in the present explosion in stent usage. But procedures should not be performed only to improve the luminal appearance, or ‘coronary cosmetology’ as stressed by Topol and Nissen. [11]

Stents are most often used for suboptimal angioplasty results despite the lack of evidence that it is of benefit for this indication. Its being used in patients with long and diffuse disease, small arteries (< 2.5 mm) aorto ostial disease and also in bifurcation lesions. At present the indications for stenting with adequate clinical evidence are:

1. Restenotic : The REST study showed a 16% incidence of clinical event at six months for stented patients compared to 28% in patients of conventional angioplasty in treatment of restenotic lesions. Target vessel revascularisation was needed in 27% of POBA patients compared to 10% in stented patients, reiterating benefits of stenting in this group of patients. [12]
2. Bailout stenting : This probably is the most important and definite indication for stenting. No interventional Cardiologist will dispute this as it restores vessel patency immediately. Trials using various stents have shown excellent immediate results. Bail out stenting has definitely higher rates of acute stent thrombosis and restenosis rate than elective stenting. The acute stent thrombosis rate has much improved after the advent of abciximab.
3. SVG Grafts : SAVED TRIAL - demonstrated that stenting is better than PTCA at 6 months though at 5 years results appear similar. Average restenosis rates of 36% and 21% which need revascularisation in follow up of upto 65 months. [10]
4. Acute MI : Studies have shown high success rates with few complications. The PAMI stent Pilot trial, [13] has shown that primary stenting in acute myocardial infarction, even in thrombus containing lesions is safe with very few instances of stent thrombosis. However, rate of death, re MI, recurrent ischaemia, stroke, new onset congestive heart failure were not significantly different in stent and PTCA only groups.

CONCLUSION

Stenting is definitely the most important break through in cardio vascular medicine since the advent of balloon angioplasty. It is a welcome innovation for the interventionist, especially to get out of tight situations like bail out indications. For elective usage the costs are prohibitive.

There is evidence from published trials that compared to POBA elective stenting of discrete new onset and restenotic lesions in native arteries improves clinical and angiographic outcomes at 6 months. [14] Other indications being discrete lesions in saphenous vein grafts and probably in chronic total occlusions. There is a lack of objective evidence in favour of stents being used in many other situations. Stents have improved the safety of interventions, has decreased the need for emergency CABG and restored vessel patency in acute or threatened vessel closure during balloon angioplasty. Stents improve angiographically unsatisfactory results of angioplasty. Trials that support stenting for primary prevention of restenosis are undermined by operator bias. Each clinical situation is to be judged individually by the operator. Guidelines have to be drawn up for the optimal use of stents, primary or secondary. The problem of instent restenosis should be effectively addressed. The efficacy of stenting for complex lesions should be proved. The costs are to be reduced and late sequelae with permanent endovascular metallic devices should be completely ruled out.

Will elective stenting prove to be more effective than aggressive POBA with provisional stenting? At present we do not know. It is difficult to justify the primary and excessive use of stents in the majority of percutaneous coronary intervention which may appear to be for "INSTENT - GRATIFICATION" than for proven efficacy. Interventionists should exercise constraint and be selective in device usage without misusing them for a mere more gratifying angiogram, in the absence of a clear documentation of clinical advantage. Stenting should be an adjunct to POBA rather than an alternative. From the data available at present, an initial aggressive POBA followed by a reactive stenting, if necessary, should be the accepted strategy. Some parameters for stenting would be 1) actual or threatened closure, 2) dissection of more than 10 mm in length, 3) a residual narrowing of over 30% in a vessel which is 2.5 mm or more in size. A cost benefit analysis for other indications will provide important insight and information.

ACKNOWLEDGEMENT

I thank my wife Dr. Rekha and Senior Resident Dr. Nanda Kishore, in preparing this manuscript.

REFERENCES

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11. Eric J Topol. Our preoccupation with coronary luminology. The dissociation between clinical and angiographic findings in IHD. Circulation 1995; 92 : 2333-42.
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13. Grigg W Stone, Bruce R Brodic, John J Griffin, et al. Prospective multicentric study of the safety and feasibility of Primary Stenting in acute myocardial infarction. In hospital and 30 day results of the PAMI stent pilot trial. JACC 1998; 31 : 23-30.
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