This article has Open Peer Review reports available.
Combining short stent implantation and drug-eluting stenting for routine use yields a low restenosis rate
- Ulrich Dietz1Email author,
- Cheryl Dauer1 and
- Heinz Lambertz1
https://doi.org/10.1186/1468-6708-6-18
© Dietz et al; licensee BioMed Central Ltd. 2005
Received: 21 September 2005
Accepted: 13 December 2005
Published: 13 December 2005
Abstract
Background
Stent length serves as a predictor of restenosis in use of bare metal stents (BMS). This has been demonstrated in a feasibility study that used a single short BMS implant (<9 mm) in a high proportion of lesions; the study observed a low rate of restenosis.
Methods
We performed a pilot prospective study to investigate in a series of consecutive patients the immediate and long-term effects of implantation of either 1) a single short BMS for all lesions with low probability of restenosis or 2) a drug-eluting stent (DES) for all other lesions.
Results
The 200 patients studied had 236 coronary artery lesions that were treated with short BMS in 168/236 patients (71.2%) and with DES in 68/236 patients (28.8%). Angiographic success was achieved in 230/236 lesions (97.5%) and procedural success in 194/200 patients (97.0%). Restenosis occurred in 15/153 lesions (9.8%) after short BMS, in 3/62 lesions (4.8%) after DES, and in 18/215 of all lesions (8.4%) angiographically controlled after six to eight months. Target vessel revascularization was performed in 16/218 lesion (7.4%).
Conclusion
Most of the coronary artery lesions in this small group of consecutive patients were treated sufficiently with a single BMS implant. This differential approach of treating suitable lesions in medium- to large-sized vessels with a single short BMS device and treating all other lesions with a DES implant resulted in a low incidence of restenosis.
Keywords
Introduction
Sirolimus- and Tarcolimus-eluting stents reduce restenosis rates in larger vessels and in longer lesions as compared to bare metal stents (BMS) [1, 2]. The low restenosis rates found with these drug-eluting stents (DES) suggests that all lesions could benefit from this type of stent. One concern about their use in the majority of lesions relates to cost, since these stents are much more expensive than bare metal stents [2]. A recently published cost-effectiveness analysis showed that treatment with DES would impart cost savings in patients with a BMS target vessel revascularization (TVR) rate >20% and cost effectiveness in patients with a BMS TVR rate >12% [3]. Stent length and vessel size represent primary factors affecting BMS restenosis rates [4]. Moreover, implantation of a BMS that is longer than the lesion itself increases the risk of restenosis independently [5].
In a previous prospective study, we demonstrated that stenting of only the most significant obstruction of a lesion after balloon dilatation or use of direct stenting alone was feasible in a high proportion of cases yielding low rates of stenosis. [6]. In another prospective study, we observed that short stenting significantly reduced the restenosis rate as compared to conventional stenting, which involves placement of the stent over the entire stenotic segment of a vessel [7]. In this latter study, vessel size only was found to predict restenosis after short stenting. In the present pilot study, we report on our ongoing evaluations by comparing a) short stenting with BMS in lesions with low probability of restenosis to b) stenting with DES in lesions with predicted restenosis rates of >10% after BMS.
Methods
Patients
Two hundred consecutive patients with symptoms of angina pectoris, a positive exercise tolerance test, or both, and coronary arteries with >60% diameter stenoses were included in this study. Patients with lesions in the left main artery and patients treated for myocardial infarction were excluded.
Procedures
Clopidogrel 75 mg was administered daily starting 4 days prior to elective interventions. All patients received acetylsalicylic acid for at least 14 days prior to intervention and heparin (5000 IU) as an intravenous bolus before the procedure and then by infusion during the procedure, at dose levels targeting a 2.5-fold prolongation of activated prothrombin time (aPTT). Percutaneous transluminal coronary angioplasty was performed initially in most cases using semi-compliant balloons. The balloon length was 15 mm for short lesions (<10 mm) and 20 mm for longer lesions. Balloon sizes were selected to achieve a balloon/artery ratio of 1.0 to 1.2 when fully expanded at >10 atm.
Use of BMS stents
- 1.
By direct stenting if the lesion had a length <10 mm located in the proximal part of the left anterior descending coronary artery, or of the right coronary artery; or
- 2.
After balloon dilatation of a longer lesion if angiography performed 5 min after the initial intervention showed a residual stenosis >30% that reflected a lesion ≤ 10 mm in length, in the absence of a longer dissection.
Use of DES stents
For all other lesions not suitable for a short BMS, a DES was implanted.
All stents, premounted on semi-compliant balloons, were sized to achieve a stent to artery ratio of 1.1 at >12 atm. The short BMS included 168 MultiLink stents, while the DES involved 53 Cypher stents and 15 Taxus stents. After the procedure, all patients were prescribed acetylsalicyclic acid 100 mg daily indefinitely. For patients who had received a stent, clopidogrel 75 mg daily was also prescribed for 4 weeks. Patients with hypercholesterolemia were strongly advised to take a cholesterol synthesis inhibitor regularly. Six months and eight months after implantation of the BMS and DES implants, respectively, control angiography was performed using projections that were identical to those employed during the intervention.
Quantitative coronary angiography
The CAAS II Research System (Pie Medical Imaging, Maastricht, The Netherlands) was used for automated contour detection and quantification. The system and validation data are described elsewhere [8]. The measurement procedure was previously published in detail [9]. Angiography was performed before and after all interventions and at angiographic follow-up using identical projections and analyses. Frames were selected as recommended by Herrington and Walford [10]. Analyses followed the guidelines proposed by Reiber et al. [11]. Lesion length was the distance along a vessel segment characterized by a diameter stenosis >50%, as compared to the reference segment. Lesion length, mean diameter within the lesion (mean stenosis diameter), and minimum lumen diameter (MLD) were calculated for the target vessel segment. In addition, mean diameter stenosis and minimum lumen diameter were measured at a distance of 5 mm from each stent edge. Restenosis was defined as > 50% in segment diameter stenosis at angiographic follow-up.
Statistical analyses
Continuous data are expressed as the mean ± the standard deviation. Chi-square tests were used to compare categorical variables, and the Mann-Whitney test was employed to compare continuous variables. Statistical significance was accepted at p<0.05.
Results
Baseline characteristics
Variable | All patients N = 200 |
|---|---|
Age (years) | 62 ± 10 |
Males | 154 (77.0%) |
CCS III – IV | 78 (38.0%) |
Hypertension | 153 (76.5%) |
Hypercholesterinemia | 155 (77.5%) |
Diabetes mellitus | 48 (24.0%) |
Multivessel coronary disease | 97 (48.5%) |
Lesion baseline characteristics
Variable | All lesions N = 236 |
|---|---|
De novo lesion | 227 (94.9%) |
Total occlusion | 8 (3.4%) |
Left anterior descending artery | 83 (35.2%) |
Left circumflex artery | 53 (22.5%) |
Right coronary artery | 73 (30.9%) |
Coronary artery side branches | 23 (9.7%) |
Venous coronary bypass | 4 (1.7%) |
Lesion morphology | |
Eccentric | 157 (66.5%) |
Diffuse | 33 (14.0%) |
AHA type A/B1 | 93 (39.4%) |
AHA type B2/C | 143 (60.6%) |
Procedural data and baseline characteristics of quantitative coronary angiography
Variable | Short BMS n = 168 | DES n = 68 | p | All Stents n = 236 |
|---|---|---|---|---|
Stent length (mm) | 8.3 ± 0.2 | 18.4 ± 5 | <0.0001 | 11.2 ± 8 |
Nominal device diameter (mm) | 3.0 ± 0.4 | 2.7 ± 0.2 | <0.0001 | 2.9 ± 0.5 |
Inflation pressure (atm) | 13 ± 3 | 13 ± 3 | ns | 13 ± 3 |
Device/artery ratio | 1.12 ± 0.1 | 1.14 ± 0.1 | ns | 1.13 ± 0.1 |
Reference diameter (mm) | 3.1 ± 0.4 | 2.8 ± 0.3 | <0.0001 | 3.0 ± 0.5 |
Diameter stenosis before (%) | 74 ± 14 | 76 ± 13 | <0.0001 | 75 ± 14 |
MLD before (mm) | 0.77 ± 0.4 | 0.73 ± 0.4 | ns | 0.76 ± 0.3 |
Plaque area (mm2) | 9 ± 5 | 14 ± 7 | 0.0001 | 10 ± 6 |
Lesion length (mm) | 8.7 ± 3 | 14.6 ± 5 | <0.0001 | 9.8 ± 5 |
Angiographic analysis revealed that residual plaque outside the short BMS contributed to 25% to 45% residual diameter stenosis in 15/168 (8.9%) lesions, and none after DES implantation.
Immediate results
Clinical and angiographic outcomes
Variable | All lesions n = 236 |
|---|---|
Angiographic success | 230 (97.5%) |
Procedural success | 194/200 (97.0%) |
Final minimum lumen diameter (mm) | 2.9 ± 0.3 |
Final diameter stenosis (%) | 15 ± 12 |
Acute gain (mm) | 2.2 ± 0.3 |
Final plaque area (mm2) | 2.8 ± 2.2 |
Clinical follow-up
Angina pectoris (Canadian Cardiovascular Society classes III or IV) recurred during follow-up in 3 patients, and major cardiac events were experienced by 3 patients, of whom 2 died during the 8-month follow-up period while the third underwent elective coronary artery bypass grafting. Target vessel revascularization was performed in 16/218 (7.4%) lesions at follow-up.
Angiographic follow-up
Angiographic follow-up
Variable | All lesions n = 215 |
|---|---|
Percent diameter stenosis | 33 ± 20 |
Minimum lumen diameter (mm) | 2.3 ± 0.6 |
Late loss (mm) | 0.58 ± 0.5 |
Loss index | 26 ± 15 |
Net gain (mm) | 1.5 ± 0.7 |
Net gain index | 51 ± 24 |
Neo-plaque area (mm2) | 1.8 ± 3.5 |
Net plaque reduction (mm2) | 6.2 ± 4 |
Restenosis (%) | 18 (8.4%) |
Discussion
Although BMS implants in many lesions have reduced the restenosis rate as compared to PTCA, stent implantation in the clinical setting continues to yield restenosis rates exceeding 20% [12]. In general, in-stent restenosis (ISR) can be predicted based on stent size and stent length and based on the presence of diabetes mellitus [4, 13]. Previous analyses have demonstrated that stent length can serve as a predictor of ISR independent of lesion length [14, 15]. A recent meta-analysis of intervention trials noted that stent length exceeds lesion length in about 90% of interventions; this excess in stent length increased the risk of ISR independent of other parameters in bare metal stenting [5].
In a previous study investigating the feasibility of routinely shortening stent length to cover only those vessel segments with significant obturating plaque and leaving nonobstructing plaque material unstented, we found it suitable to use a single stent <10 mm in 60% of all stent implantation procedures [6]. The 6-month angiographic restenosis rate in this study was 16% for all stented lesions. In a prospective study of 400 consecutive patients who underwent short stenting of their coronary artery lesions, we compared immediate and long-term results with a matched-pair control group of patients treated earlier with conventional-length stents. We found a significantly lower restenosis rate after short stenting, with no difference in the procedural success rates [7]. Vessel size was the only predictor of ISR after short stenting. In 91% of all lesions stented, the TVR rate was <10% in all vessels >2.7 mm.
With the routine use of drug-eluting stents, a lower restenosis rate can be anticipated. However, the costs of routine use of DES implants are high. A recent cost-effectiveness analysis for DES showed that these devices are cost effective when the TVR rate of BMS exceeds 12% [3].
The present pilot study was designed to demonstrate the feasibility of using short stenting in lesions with a < 10% probability of restenosis and implanting DES in all other lesions. In keeping with the results of the former investigation, a single short BMS was sufficient in the majority of interventions (252/310, 81.3%). There was a nearly 1:1 match of the stent and the lesion length. The resulting restenosis rate was within the range found in larger trials for the given stent dimensions used [13, 16].
Our protocol included percutaneous transluminal coronary angioplasty as the initial procedure for most lesions. Balloon dilatation alone achieved a low residual stenosis in only a few lesions; however, it did reduce the length of obturating plaques responsible for diameter stenoses >30%. This shortening of the significant portions of the lesions contributed to the high number of lesions that could be treated adequately with single short stents. In 5.4% of these lesions, however, their length was underestimated or a stent was misplaced, thereby requiring an additional stent, which contributed to restenosis found in the short BMS group. Plaques that were adjacent to a BMS and that caused luminal narrowing < 45% exhibited no increased frequency of restenosis. This finding is consistent with previous investigations, in which incomplete plaque coverage was not associated with increased risk for restenosis.
In conjunction with the strategy of incomplete plaque coverage, Colombo et al. introduced the concept of 'spot stenting' long lesions (>15 mm). These researchers compared a) complete coverage of a treated long lesion to b) stenting only those stenosis segments that did not meet pre-defined intravascular ultrasound criteria for successful treatment after initial balloon dilatation [17]. They observed a lower restenosis rate in the latter group. Indeed, restricting stent surface to the minimum necessary area might reduce proliferative responses of the arterial wall to the stent [18, 19].
Our findings regarding DES are comparable to those from a larger investigation of more complex lesions [1]. The overall restenosis rate of 8.4% and the TVR rate of 7.4% noted with the differential use of short bare metal stenting and DES implantation raises the question of use of DES implantation in all lesions, in terms of economic considerations. Moreover, none of the observed restenoses were diffuse or proliferative after single short BMS, a finding that is compatible with a high long-term success rate after reintervention [20].
Methodological aspects
An exact determination of lesion length was crucial to the interpretation of angiographic results. The criterion used to measure lesion length by quantitative angiography (length of plaque causing >50% diameter reduction) reflects more precisely the extent of clinically relevant stenoses and makes it possible to standardize measurements, in contrast to overall lesion length as used by many automated contour detecting systems. However, lesion length as measured by the criterion described above is usually shorter, as compared to measuring total lesion length. Since the present study was not designed to compare immediate and long-term results of short BMS and DES, we did not perform statistical comparative analysis.
Limitations
Our criteria for selecting a short BMS implant versus a DES implant for study participants were based on results from a non-randomized study performed earlier at our institution [7]. Selection of the stent device was based on operators' visual interpretation of vessel dimensions. This may, in a few cases, have led to misinterpretation of the actual reference diameter, as demonstrated by quantitative coronary angiography. In these cases, the other stent device was, therefore, implanted. Finally, the study was not randomized, since we intended to prove feasibility of the differential approach in a pilot study. A randomized multicenter trial now seems suitable to elucidate compatibility and cost-effectiveness of this approach with routine DES implantation.
Conclusion
We demonstrated that: 1) for most lesions, a single short BMS is sufficient to treat the significant part of the stenotic lesion, and 2) the resulting restenosis rate using the single short BMS is low if vessels > 2.7 mm are treated. Use of DES for all other lesions that could not be treated sufficiently with a short BMS also resulted in a low restenosis rate. These findings suggest a positive synergism between short bare metal stenting and drug-eluting stenting, in terms of reducing costs while achieving overall low restenosis rates in unselected lesions.
Declarations
Authors’ Affiliations
References
- Hill RA, Dundar Y, Bakhai A, Dickson R, Walley T: Drug-eluting stents: an early systematic review to inform policy. Eur Heart J. 2004, 25 (11): 902-919. 10.1016/j.ehj.2004.03.023.View ArticlePubMedGoogle Scholar
- O'Neill WW, Leon MB: Drug-eluting stents: costs versus clinical benefit. Circulation. 2003, 107 (24): 3008-3011. 10.1161/01.CIR.0000079018.84618.0E.View ArticlePubMedGoogle Scholar
- Greenberg D, Bakhai A, Cohen DJ: Can we afford to eliminate restenosis? Can we afford not to?. J Am Coll Cardiol. 2004, 43 (4): 513-518. 10.1016/j.jacc.2003.11.020.View ArticlePubMedGoogle Scholar
- Cutlip DE, Chauhan MS, Baim DS, Ho KK, Popma JJ, Carrozza JP, Cohen DJ, Kuntz RE: Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials. J Am Coll Cardiol. 2002, 40 (12): 2082-2089. 10.1016/S0735-1097(02)02597-4.View ArticlePubMedGoogle Scholar
- Mauri L, O'Malley AJ, Cutlip DE, Ho KK, Popma JJ, Chauhan MS, Baim DS, Cohen DJ, Kuntz RE: Effects of stent length and lesion length on coronary restenosis. Am J Cardiol. 2004, 93 (11): 1340-6, A5.. 10.1016/j.amjcard.2004.02.027.View ArticlePubMedGoogle Scholar
- Dietz U, Holz N, Dauer C, Meinert R, Lambertz H: Short stent implantation for routine use is feasible in a high proportion of coronary interventions and yields a low restenosis rate. Cardiology. 2005, 103 (4): 212-218. 10.1159/000085200.View ArticlePubMedGoogle Scholar
- Dietz U, Holz N, Dauer C, Lambertz H: Shortening the stent length reduces restenosis with bare metal stents: matched-pair comparison of short stenting and conventional stenting. Heart. 2005Google Scholar
- Hausleiter J, Jost S, Nolte CW, Dirschinger J, Kastrati A, Stiel GM, Wunderlich W, Fischer F, Linderer T, Hausmann D, Schomig A: Comparative in-vitro validation of eight first- and second-generation quantitative coronary angiography systems. Coron Artery Dis. 1997, 8 (2): 83-90.View ArticlePubMedGoogle Scholar
- Dietz U, Rupprecht HJ, Brennecke R, Fritsch HP, Woltmann J, Blankenberg S, Meyer J: Comparison of QCA systems. Int J Card Imaging. 1997, 13 (4): 271-280. 10.1023/A:1005768523234.View ArticlePubMedGoogle Scholar
- Herrington DM, Walford GD: Optimal frame selection for QCA. Advances in Quantitative Coronary Arteriography. Edited by: Reiber JHC SPW. 1993, The Netherlands , Kluwer Academic Publishers, 125-135.View ArticleGoogle Scholar
- Reiber JH, van Eldik Helleman P, Visser Akkerman N, Kooijman CJ, Serruys PW: Variabilities in measurement of coronary arterial dimensions resulting from variations in cineframe selection. Cathet Cardiovasc Diagn. 1988, 14 (4): 221-228.View ArticlePubMedGoogle Scholar
- Kastrati A, Mehilli J, Dirschinger J, Pache J, Ulm K, Schuhlen H, Seyfarth M, Schmitt C, Blasini R, Neumann FJ, Schomig A: Restenosis after coronary placement of various stent types. Am J Cardiol. 2001, 87 (1): 34-39. 10.1016/S0002-9149(00)01268-6.View ArticlePubMedGoogle Scholar
- Serruys PW, Kay IP, Disco C, Deshpande NV, de Feyter PJ: Periprocedural quantitative coronary angiography after Palmaz-Schatz stent implantation predicts the restenosis rate at six months: results of a meta-analysis of the BElgian NEtherlands Stent study (BENESTENT) I, BENESTENT II Pilot, BENESTENT II and MUSIC trials. Multicenter Ultrasound Stent In Coronaries. J Am Coll Cardiol. 1999, 34 (4): 1067-1074. 10.1016/S0735-1097(99)00308-3.View ArticlePubMedGoogle Scholar
- Kereiakes D, Linnemeier TJ, Baim DS, Kuntz R, O'Shaughnessy C, Hermiller J, Fink S, Lansky A, Nishimura N, Broderick TM, Popma J: Usefulness of stent length in predicting in-stent restenosis (the MULTI-LINK stent trials). Am J Cardiol. 2000, 86 (3): 336-341. 10.1016/S0002-9149(00)00928-0.View ArticlePubMedGoogle Scholar
- Kobayashi Y, De Gregorio J, Kobayashi N, Akiyama T, Reimers B, Finci L, Di Mario C, Colombo A: Stented segment length as an independent predictor of restenosis. J Am Coll Cardiol. 1999, 34 (3): 651-659. 10.1016/S0735-1097(99)00303-4.View ArticlePubMedGoogle Scholar
- Antoniucci D, Valenti R, Santoro GM, Bolognese L, Trapani M, Cerisano G, Boddi V, Fazzini PF: Restenosis after coronary stenting in current clinical practice. Am Heart J. 1998, 135 (3): 510-518. 10.1016/S0002-8703(98)70329-1.View ArticlePubMedGoogle Scholar
- Colombo A, De Gregorio J, Moussa I, Kobayashi Y, Karvouni E, Di Mario C, Albiero R, Finci L, Moses J: Intravascular ultrasound-guided percutaneous transluminal coronary angioplasty with provisional spot stenting for treatment of long coronary lesions. J Am Coll Cardiol. 2001, 38 (5): 1427-1433. 10.1016/S0735-1097(01)01557-1.View ArticlePubMedGoogle Scholar
- Komatsu R, Ueda M, Naruko T, Kojima A, Becker AE: Neointimal tissue response at sites of coronary stenting in humans: macroscopic, histological, and immunohistochemical analyses. Circulation. 1998, 98 (3): 224-233.View ArticlePubMedGoogle Scholar
- Inoue T, Sohma R, Miyazaki T, Iwasaki Y, Yaguchi I, Morooka S: Comparison of activation process of platelets and neutrophils after coronary stent implantation versus balloon angioplasty for stable angina pectoris. Am J Cardiol. 2000, 86 (10): 1057-1062. 10.1016/S0002-9149(00)01159-0.View ArticlePubMedGoogle Scholar
- Mehran R, Dangas G, Abizaid A, Lansky AJ, Mintz GS, Pichard AD, Satler LF, Kent KM, Waksman R, Stone GW, Leon MB: Treatment of focal in-stent restenosis with balloon angioplasty alone versus stenting: Short- and long-term results. Am Heart J. 2001, 141 (4): 610-614. 10.1067/mhj.2001.113998.View ArticlePubMedGoogle Scholar
Copyright
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Please note that comments may be removed without notice if they are flagged by another user or do not comply with our community guidelines.