Outcomes of Overlapping Bare-Metal Stents with Sirolimus-Eluting Stents for Long Lesions in Small Coronary Vessels

ABSTRACT: Objectives. Compare outcomes of hybrid bare-metal stent (BMS)/sirolimus-eluting stent (SES) to BMS alone for the treatment of stenoses in small coronary arteries. Background. One approach to potentially reduce the risk of restenosis in long lesions with smaller distal reference diameters is to use a small (2.0–2.5mm) “BMS cap” (BMC) distally, telescoped in tandem with a SES(s) proximally, matched to a proximal segment where the diameter is ≥ 2.5 mm (creating a BMC/SES hybrid stent). Results from previous reports using “hybrid” drug-eluting stents and BMS are mixed. Methods. We performed a retrospective analysis of BMC/SES cases in small vessels at our institution and compared the outcomes with a control group (BMS) consisting of patients treated with at least one 2.0–2.5 mm BMS. Results. During the years 2003–2006, 41 BMC/SES and 62 BMS cases were identified and follow up was available in 33 and 49 patients, respectively. Baseline demographics, procedure indications and pertinent discharge medications for the two groups were similar. Despite the use of more stents and longer total stent length in the BMC/SES group compared to the BMS group (2.9 ± 0.79 vs. 1.4 ± 0.69 and 64 ± 21 mm vs. 26 ± 18 mm; p

J INVASIVE CARDIOL 2010;22:76–79

Key words: drug-coated stents; stents; coronary artery stenosis; coronary disease

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The relative high rate of restenosis following stent placement in smaller vessels is improved with drug-eluting stents (DES).^1–6 However, until recently with the release of the 2.25 mm Atom stent (2.31 mm at nominal pressure (9 atm) (Boston Scientific Corp., Natick, Massachusetts), the minimal DES stent diameter size available in the United States has been 2.5 mm, limiting treatment options for patients when the reference diameter of the vessel is 7 Furthermore, intravascular ultrasound and angioscopic follow up of sirolimus-eluting stents (SES) overlapped with BMS in a single patient showed that neointimal proliferation is inhibited in overlapped segment,⁸ however neointimal proliferation in the segment of the BMS without overlap is not inhibited. Prior clinical reports that investigated overlapping BMS and DES stents in de-novo lesions (both large and small vessels) have shown relatively high target vessel revascularization (TVR) rates of 32%.⁹ Whether or not clinical outcomes can be improved with the use of a BMC distally combined with a SES proximally in small coronary vessels is not known. Here we retrospectively compare the clinical outcomes of lesions with ≤ 2.5 mm distal reference vessel treated with a BMC/SES hybrid stent compared to those treated with a BMS alone.

Materials and Methods

Institutional review board approval was given by the Mayo Clinic and Midwestern University ethics committees. We performed a retrospective chart review of all patients treated with BMC/DES hybrid stents (BMC ≤ 2.5 mm) at Mayo Clinic Arizona (Phoenix, Arizona) from 2004–2007, searching all lesions treated with either a Pixel (Guidant Corp., Indianapolis, Indiana), a Minivision (Abbott Vascular, Santa Clara, California), or a Microdriver (Medtronic, Inc., Minneapolis, Minnesota) stent in tandem with a DES. The control population patients treated with at least one BMS ≤ 2.5 mm (and no DES at that lesion) at Mayo Clinic Arizona from 2002–2007 was identified as any lesion treated with either a Pixel, Minivision or Microdriver stent and no DES. If ≥ 6-month clinical outcomes were not available from medical records, a follow-up questionnaire (and consent) was mailed to the patient. Restenosis was defined as a lesion diameter stenosis > 50%. Major adverse cardiac events (MACE) were defined as the composite of cardiac death, myocardial infarction (MI) and restenosis. Dichotomous variables were analyzed by either the chi-square or Fisher’s exact test, as appropriate. Continuous data were analyzed using the Student’s t-test. Averages are shown ± the standard deviation. Statistical significance was determined to be p Results Forty-one BMC/DES hybrid stent patients were identified and 62 patients BMS (control) patients were identified. Patients were excluded if they refused to sign the consent (Authorization to Use and Disclose Protected Health Information Form) or if no endpoint had occurred with follow up of 10 for the three BMC/SES patients were: 1 (33%) Class 1C (focal body) involving the DES, 1 (33%) Class IV (total occlusion) involving the BMC, and 1 (33%) Class IV involving both the DES and BMC. In all patients from the BMC/SES group with restenosis, the BMS(s) was placed first and the SES(s) was placed second (SES “inside” of BMS). Two of the patients were treated with repeat PCI (1 with BMS and 1 with DES) and the third patient was treated with medical therapy. At last follow up for these 3 patients, all were alive without angina and none had a subsequent MI. The patterns of restenosis for the 8 BMS patients were: 2 (25%) Class IB (focal margin), both involving the proximal stent edge, 3 (38%) Class IC (focal body), 1 (13%) Class II (diffuse, intrastent), and 2 (25%) Class IV (total occlusion). Six (75%) of these patients were treated with re-PCI and 2 (25%) with coronary artery bypass graft surgery. One patient developed recurrent restenosis treated with re-PCI. At last follow up for these 8 patients, all other were alive and angina-free.

Discussion

We performed a retrospective comparison of patients treated at our institution with BMC/SES hybrid stents versus BMS alone for lesions with a distal reference vessel ≤ 2.5 mm. Long-term clinical follow up was available for approximately 80% of the 103 patients identified, and was similar in the two groups. The length of follow up was also similar between the groups. The groups also seemed well matched with respect to patient demographics. Despite longer total length of stents and more stents used per lesion, the patients treated with BMC/SES had significantly fewer MACE than the patients receiving BMS alone (9% vs. 29%). Treatment options for coronary stenoses in vessels 11,12 PTCA and cilastazol,¹³ cutting-balloon angioplasty,¹⁴ rotational atherectomy,¹⁵ and BMS^11,12 have relatively high restenosis rates. Rates are improved with DES,^1–4,6 however, stent sizes available (especially in the U.S. where the 2.25 mm Atom paclitaxel-eluting stent [PES] was just released recently, but other 2.25 mm DES remain unavailable) limit the lesions treatable by DES. The goal of our study was to evaluate outcomes in vessels in which the distal vessel was too small for safe placement of a DES, requiring a small BMS, or “bare-metal cap” (BMC) distal followed by a proximal DES(s) in tandem with the BMC. In our study patients, SES were used exclusively, as it was our preferred DES in small vessels during the time period of the study. Subsequent literature supports the superiority of SES compared to PES in small vessels.^16,17 As a control group, we chose lesions treated with BMS alone with a distal stent diameter ≤ 2.5 mm. We anticipated that the study design would favor the BMS group, as total length of stents and number of stents used would be less. Despite this, outcomes in the BMC/SES group compared favorably to the BMS group. In fact, from these data, one could argue that if the vessel is too small to enact “bigger is better”, then perhaps one should achieve “longer is better” using an SES. In this case, if the patient does develop in-stent restenosis in the SES, it is more likely to be focal and more easily treated.^3,17 Clinical restenosis and TLR rates (9% and 6%) appear comparable to those of published angiographic trials for DES alone in small vessels (in-segment restenosis ranging from 2–31%).¹⁸ Our conclusions differ from a previously published retrospective study on hybrid BMS/DES stents.9 However, there are many differences between this and the current study, making direct comparisons difficult. In the study, 44 patients were enrolled who were treated with overlapping DES and BMS and included all lesions, regardless of vessel diameter. The average stent diameter was 2.35 mm for the BMS which is larger than the 2.1 mm found in the current and lesion lengths in this previously published study were shorter (lesion length 17.8 mm versus total stent length 64 mm in the current study). Also, in the prior study, there was no control group and 44% of patients received at least 1 PES (current study is 100% SES). Quite different from our study, the authors found a TVR rate at 12 months of 31.8% and concluded that overlapping BMS and DES stents are associated with a high rate of TVR. It is not clear to what extent sirolimus delivery distal to the SES may be important for the presumed efficacy of BMC/SES. Two observations from clinical studies are consistent with the idea that drug is delivered to vessel distal to the DES: 1) focal edge restenosis in either SES or PES is more common proximally than distally;¹⁹ and 2) there is abnormal vasoconstriction distal to either SES or PES.²⁰ If, in fact, drug is delivered distally, then maximizing distal delivery may be important with regard to decreasing restenosis. Intuitively, it would seem that drug exposure to the vessel wall from the abluminal surface of the stent would be most important, and this would dictate that the SES should be delivered before the BMC (BMC “inside” SES). However, mathematical models and animal studies7 suggest that the adluminal surface contributes more to drug delivery than the abluminal surface, arguing that the BMC should be delivered before the SES (SES “inside” BMC). Intravascular ultrasound studies of neointimal formation in the distal (BMS) segment of lesions treated with BMC/SES (differentiating between the two potential deployment sequences noted above) could be useful to document what, if any, efficacy sirolimus has downstream of the SES. Study limitations. The utility of our findings may be diminished with the release of the Atom PES. How the BMC/SES compares to the Atom in longer lesions (> 28 mm requiring overlapping stents) is not known. Other limitations to our study include the retrospective and nonrandomized nature. Potential bias as to which patients received BMC/SES and which received BMS is of concern, and evidence of this may be the trend towards non-cardiac death (3% vs. 6%), as sicker patients with other comorbidities are probably less likely to receive DES due to their associated longer duration of thienopyridine therapy. Other major limitations include the small sample size, approximately 80% follow up, and a single center for data collection. The small size limits subgroup analysis and does not allow for multivariate analysis. Finally, the follow-up questionnaire may be subject to self-selection bias as well as a self report bias.

Conclusions

In patients with stenoses in small coronary vessels ≤ 2.5 mm, there was an observed clinical benefit using BMC/SES as the results compared favorably to a cohort of patients treated with BMS alone. Our findings support the use of BMC/SES in small vessels. Whether or not these finding extend to other DES is not known. Future prospective randomized studies are warranted.

References

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___________________________________________ From ^*Midwestern University, Glendale, Arizona, and ^§Mayo Clinic Arizona, Phoenix, Arizona. The authors report no conflicts of interest regarding the content herein. Manuscript submitted July 6, 2009, provisional acceptance given August 3, 2009, final version accepted August 14, 2009. Address for correspondence: F. David Fortuin, MD, Cardiology, 5777 E. Mayo Blvd., Phoenix, AZ 85054. E-mail: fortuin.david@mayo.edu