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Unique Challenges of Full Metal Jackets in the Era of Drug-Eluting Stents
From the Division of Cardiology, Hawaii Region Kaiser Permanente, Honolulu, Hawaii. The author reports no conflicts of interest regarding the content herein. Address for correspondence: Paul C. Ho, MD, FACC, FSCAI, Chief, Division of Cardiology, Hawaii Region Kaiser Permanente, 3288 Moanalua Road, Honolulu, HI 96819. E-mail: paul.c.ho@kp.org
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J INVASIVE CARDIOL 2009;21:51–42
“Full metal jacket” refers to extensive stent coverage of a very long segment to most of the length of the coronary artery. Extensive stent coverage is often necessary due to the diffuse nature of coronary arterial disease, and is often associated with long-standing atherosclerosis and risk factors such as diabetes and chronic total occlusions (CTO). In the days of bare-metal stents (BMS), long stented coronary segments were associated with high in-stent restenosis (ISR) rates in the order of 40% or more within 6 months.1 Although drug-eluting stents (DES) have significantly reduced the rates of ISR across multiple subsets of coronary lesions including very long stenoses, the continued appearance of late to very late stent thrombosis remains a concern and may be a unique issue with DES.
In early randomized clinical trials (RCT), the use of DES significantly reduced the incidence of ISR to approximately 5%, however, the same antiinflammatory/antiproliferative drugs and polymers responsible for the success of DES may be associated with an observed trend toward late to very late stent thrombosis, mostly attributed to delayed endothelialization of the metallic stent struts. In a pooled data analysis from a RCT of 1,748 patients,2 there was no statistical difference in stent thrombosis between BMS versus DES over a 4-year follow-up period. Within 1 year from stent implantation, however, stent thrombosis rates were significantly higher for DES: none for BMS versus 5 for sirolimus-eluting stents (p = 0.025); and 2 for BMS versus 9 for paclitaxel-eluting stents (p = 0.028). In the same study, both DES were found to be associated with lower rates of target lesion revascularization and no significant difference in cumulative rates of death or myocardial infarction.
The discomfort of late to very late stent thrombosis with DES is further magnified in the more complex “real-world” patients whose coronary lesions are longer, more diffuse, located in smaller vessels, are more angulated, more calcified and involve more side-branch issues compared to the preselected patients from RCT. A potentially useful risk prediction model for “real-world” stent thrombosis was developed from the ARRIVE 1 post-market data registry for the Taxus® Express 2 stent (Boston Scientific Corp., Natick, Massachusetts).3 A total of 8 clinical and angiographic predictors were determined to be most significant including: early discontinuation of thienopyridine, long stent length (> 28 mm), multiple stents, small vessel diameter (4 Though not a randomized study, practical information may be derived from the model. Based on the risk predictors, the score model discriminated low-, medium- and high-risk patient groups receiving DES for stent thrombosis. Analysis of patients from both the ARRIVE 1 and 2 registries found only 2% of patients in the high-risk category, which corresponded to a 12.6% rate of stent thrombosis in 1 year and 25% of patients in the medium-risk group with a 3.6% stent thrombosis rate. The rest belonged to the low-risk group, with 0.6% stent thrombosis.
Along with a current estimated 50% off-label use of DES in all of percutaneous coronary interventions, the article by Andron et al is relevant to the study of keys issues in the “real-world” use of DES, as with the ARRIVE registry. Although it involved a small sample size of 88 patients undergoing 91 single-vessel stent placement procedures, the unique feature of this study is that all patients have had very long segments of overlapping DES (> 50 mm), with a mean stent length of 70.6 mm (range: 51–135 mm). Patients with ISR and saphenous vein graft disease were excluded. The authors reported that 3/88 patients developed very late stent thrombosis (> 1 year) at a rate of 3.4%. Without direct application of the ARRIVE risk model, this finding appears to be within the range of other observations. All of the patients with very late stent thrombosis had discontinued clopidogrel at 12 months, which correlated with a similar finding from the ARRIVE model. As the authors also concluded, routine use of IVUS in this subset of patients may help to minimize the stent thrombosis rate by optimal stent apposition to the vessel wall,5 as would the traditional recommendation of high-pressure post-dilatation with noncompliant balloons.
Several observations of endothelial dysfunction associated with DES may add to the concern for long-term issues, especially when the stent burden is high. In several small studies, sirolimus-eluting stents implanted in human coronary arteries were associated with significant local endothelial dysfunction and a reduction in myocardial VEGF (vascular endothelial growth factor) secretion compared to BMS.6–8 A resemblance of a DES full metal jacket to a saphenous vein graft with respect to the issues of endothelial dysfunction and long-term durability is implied. Further studies in this area are necessary to address the long-term concern of endothelial dysfunction with extensive DES implantation.
In the era of DES, increased stent coverage has become the trend due to its superior performance in lowering ISR. As more complex and advanced disease subtypes are being treated, e.g., CTOs, longer stent segments and more overlapping stents will continue to be used. Risk stratification models such as that derived from the ARRIVE study may help to guide a stepwise recommendation for the duration of aspirin and clopidogrel administration. The routine conscientious practice of intravascular ultrasound use and high-pressure postdilatation for complex lesion types can minimize long-term complications. In patients with DES full metal jackets, careful follow up and monitoring for long-term adverse events are required.
References
1. Kim YH, Park SW, Lee CW, et al. Comparison of sirolimus-eluting stent, paclitaxel-eluting stent and bare metal stent in the treatment of long coronary lesions. Catheter Cardiovasc Interv 2006;67:181–187. 2. Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med 2007;356:998–1008. 3. Russell ME, Friedman MI, Mascioli SR, Stolz LE. Off-label use: An industry perspective on expanding use beyond approved indications. J Interv Cardiol 2006;19:432–438. 4. Baran KW, Lasala JM, Cox DA, et al; ARRIVE Investigators. A clinical risk score for prediction of stent thrombosis. Am J Cardiol 2008;102:541–545. 5. Cook S, Wenaweser P, Togni M, et al. Incomplete stent apposition and very late stent thrombosis after drug-eluting stent implantation. Circulation 2007;115:2426–2434. 6. Hofma SH, van der Giessen WJ, van Dalen BM, et al. Indication of long-term endothelial dysfunction after sirolimus-eluting stent implantation. Eur Heart J 2006;27:166–170. 7. Fuke S, Maekawa K, Kawamoto K, et al. Impaired endothelial vasomotor function after sirolimus-eluting stent implantation. Circ J 2007;71:220–225. 8. Obata JE, Kitta Y, Takano H, et al. Sirolimus-eluting stent implantation aggravates endothelial vasomotor dysfunction in the infarct-related coronary artery in patients with acute myocardial infarction. J Am Coll Cardiol 2007;50:1305–1309.
