Acute Myocardial Infarction Caused By Late Stent Thrombosis after Deployment of a Paclitaxel-eluting Stent

Since the use of combined antiplatelet therapy with aspirin and thienopyridines, the incidence of stent thrombosis is uncommon. Moreover, late stent thrombosis (> 30 days after stent implantation) is extremely rare with bare metal stents except after intracoronary irradiation, which delays vascular healing. However, clinical outcomes of stent thrombosis are severe catastrophic and most cases usually result in ST-segment elevation myocardial infarction or death. Recently, polymer-based drug-eluting coronary stents, which effectively inhibit neointimal hyperplasia that results in reducing the need for repeat percutaneous coronary intervention and the incidence of major adverse cardiac events (MACE), are rapidly replacing bare metal stents. Like intracoronary irradiation, because of delayed endothelialization of the stent, drug-eluting stents may also be susceptible to late stent thrombosis.^1,2 We report one case of a patient with acute myocardial infarction due to late stent thrombosis when clopidogrel was discontinued after deployment of a paclitaxel-eluting stent. Case Report. A 56-year old male patient came to our hospital due to severe chest pain that had lasted for 12 hours. He was a smoker for 35 years. However, the patient had no history of diabetes, hypertension or hyperlipidemia. Fourteen months prior, he admitted to the hospital due to an ST-segment elevation acute inferior wall myocardial infarction. Coronary angiography showed total occlusion of the proximal right coronary artery (RCA) with thrombus (Figure 1A) and diffuse, severe, irregular stenosis of the proximal left anterior descending (LAD) artery (Figure 1B). Severely narrow lesions in the distal left circumflex (LCX) artery and the ostial obtuse marginal (OM) artery were also noted. Primary percutaneous coronary intervention (PCI) was performed successfully in the proximal segment lesion of the RCA with deployment of a 3.0 x 16 mm bare metal JoStent® (Abbott Vascular Devices, Redwood City, California) (Figure 1C). Two weeks after primary PCI, the patient received a 3.0 x 32 mm Taxus™ Express 2™ paclitaxel-eluting stent (Boston Scientific, Maple Grove, Minnesota) in the proximal segment of the LAD without any complications (Figure 1D). The patient was then discharged and put on continuous combined antiplatelet medication with aspirin and clopidogrel. At 9-month follow-up, angiography revealed good patency in both stents, with no restenosis (Figure 2 A and B). IVUS examination revealed that many parts of the paclitaxel-eluting stent implanted at the proximal segment of the LAD were not covered by intimal hyperplasia (Figure 2C). After 2 months of combined antiplatelet treatment and another follow-up angiography, the patient was switched from the combined antiplatelet treatment with aspirin and clopidogrel to aspirin alone. Fourteen months after stent deployment and 6 weeks after the discontinuation of clopidogrel, the patient suffered severe chest pain for 12 hours and returned to our emergency room. Marked ST-segment elevation was noted at the precordial leads on ECG, and cardiac enzymes were also markedly elevated. The subsequent coronary angiography demonstrated stent thrombosus at the proximal edge of the paclitaxel-eluting stent, with total occlusion of the proximal LAD (Figure 3B), with collaterals from the right coronary system filling the distal part of the vessel, whereas the bare metal stent implanted at the proximal RCA was patent (Figure 3A). The patient received a 3.0 x 38 mm Multi-Link Penta® bare metal stent (Guidant Corporation, Indianapolis, Indiana) at the proximal occlusion site of the LAD. Coronary angiography after stenting showed restoration of normal coronary blood flow (Figure 3C). Discussion. Stent thrombosis after bare-metal stenting is a rare but catastrophic complication. This event typically presents in the first few days after the procedure, almost thrombosis causes an acute myocardial infarction or death. Because thrombosis is associated with inadequate stent expansion, implementation of high-pressure stent deployment in conjunction with combined antiplatelet therapy with aspirin and thienopyridine, reduce stent thrombosis rates to under 2%.³ In our case, we confirmed full expansion of stent immediate after procedure and late stent malapposition which cause thrombosis was not noted on follow-up IVUS examination. Because bare-metal stents become endothelialised within a few weeks of implantation, using combined antiplatelet therapy for 2 to 4 weeks after stenting is sufficient for prevention of late stent thrombosis. In contrast, drug-eluting stents might cause late stent thrombosis for far extended period after stent implantation due to delayed or incomplete reendothelialisation of the stent struts in addition to stent thrombogenicity or neointimal dysfunction determined by drug. Animal study with drug-eluting stent indicated that vascular healing is arrested, with sustained presence in the neointima of inflammatory cells as part of this delayed healing.⁴ Such an incomplete healing process may prolong the period of vessel wall thrombogenicity, as observed after endovascular radiation therapy. However, animal studies showed that re-endothelialiszation of the injured segment was affected only at a high dose of paclitaxel, so these results cannot be directly transferred to the human situation. Currently, the most appropriate duration of treatment with this antiplatelet therapy required to prevent this complication is still controversial. Based on the pivotal clinical trials that led to approval of such stents, trial protocols with these stents have mandated more prolonged antiplatelet therapy than earlier trials with bare-metal stents. Dual antiplatelet therapy is prescribed on an empirical basis, for 2 to 3 months after implantation of sirolimus-eluting stents, and for 6 months after implantation of paclitaxel-eluting stents, with life-long aspirin. In our case, paclitaxel-eluting stent was occluded by thrombosis rather than neointimal hyperplasia for reasons that neointimal hyperplasia was not noted follow-up IVUS examined after 9 months of stenting and a bare-metal stent implanted at RCA at the same time, remained patent. And because late stent malappoistion was not noted at follow-up IVUS, discontinuation of clopidogrel is contributing factor causing late stent thrombosis. Our report shows that thrombosis can arise very late (> 1 year after stenting) after uncomplicated placement of a paclitaxel-eluting stent, in a large vessel, when clopidogrel therapy is discontinued, even though without discontinuation of aspirin. Recently, McFadden et al. reported four cases of late stent thrombosis after discontinuation of antiplatelet therapy.⁵ They stopped prescription of aspirin or aspirin/clopidogrel for non-cardiac surgery or other reason. Compared to those cases, different points in our case are that we maintained antiplatelet therapy with aspirin after discontinuation of clopidogrel, and they did not performed follow-up angiography before development of late stent thrombosis. Therefore they could not exclude definitely possibility of neointimal hyperplasia rather than thrombosis as cause of total occlusiojn of coronary artery except one case who was performed IVUS examnination. In conclusion, until large studies address the timing of complete vessel healing after paclitaxel eluting stent implantation or the role of endothelial dysfunction is better defined, the clinician should consider the use of combined treatment with two antiplatelet agents indefinitely(aspirin plus ticlopidine or aspirin plus clopidogrel) after implantation of paclitaxel-eluting stent, especially in case who intimal hyperplasia is not noted within stent on follow-up IVUS like our one which might be meaning of incomplete vascular healing. ahnth@gilhospital.com

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