Acute stent thrombosis is a rare but serious complication of stent implantation. Although anecdotal reports suggest that the use of drug-eluting stents (DES) may increase the risk of stent thrombosis, this has not been borne out in randomized, controlled trials. We report a case of acute stent thrombosis following implantation of a DES, with review of the literature. Despite the initial favorable procedural result, the patient developed stent thrombosis 7 days later; intravascular ultrasound (IVUS) demonstrated incomplete deployment of the stent. We recommend the use of IVUS in the management of acute stent thrombosis in order to exclude incomplete stent expansion which may underlie acute thrombotic occlusion.

       Compared with bare metal stents (BMS), drug-eluting stents (DES) significantly reduce the risk of restenosis and the subsequent need for revascularization.¹ Stent thrombosis remains a serious complication with either BMS or DES, with an incidence of 0.5–1.9% with BMS.^2–3 The sequelae are serious: in one study, nonfatal myocardial infarction occurred in 69% of cases and death, in 45%.⁴ Suggested mechanisms include delayed endothelialization, enhanced platelet aggregation and intrinsic patient factors, such as resistance to antiplatelet agents. Mechanical factors such as stent underdeployment may also contribute to stent thrombosis.

Figure 1

(A) RAO caudal projection after stenting the left circumflex artery demonstrating a good result. White line indicates stented segment. (B) RAO caudal projection demonstrating occlusion of the left circumflex artery within the stented segment one week later.

       Anecdotal reports have raised the possibility that stent thrombosis may be more frequent in patients who have received DES.5 Factors more specific to DES technology that may increase the risk of stent thrombosis include delayed endothelialization and possible hypersensitivity to the stent polymer.

Figure 2

IVUS images from the distal (E) to proximal left circumflex artery (A). The minimal lumen area was measured at 2 mm2 (C) which corresponds to the arrowed segment. There is gross underexpansion of the stent struts within 360º of heavy calcification (C). The distal stent (D) and vessel beyond (E) demonstrate extensive thrombus (asterisks).

       Case Report. A 72-year-old male underwent staged percutaneous coronary intervention (PCI) for double-vessel coronary artery disease. Following successful stenting of the left anterior descending artery, he underwent PCI to the circumflex vessel. Due to heavy calcification, high-pressure predilatation was performed using a 3.0 mm cutting balloon. A 3.0 x 23 mm Cypher™ stent (Cordis Corporation, Miami, Florida) appeared well expanded at 12 atmospheres, achieving a good angiographic result (Figure 1). However, 1 week after discharge, he was readmitted with an acute coronary syndrome. Repeat angiography demonstrated stent thrombosis and total occlusion of the circumflex artery (Figure 1). The occlusion was gently dilated using a

Figure 3

IVUS images from the distal (E) to proximal left circumflex artery (A) following aggressive balloon dilatation. The calcification has been disrupted with improved stent expansion (C). Asterisks mark extensive thrombus which remains in the distal stent (E) and beyond the stented segment (E).

3.0 mm balloon. Intravascular ultrasound (IVUS) showed extensive thrombus with concentric failure of expansion of the stent in a heavily calcified vessel (Figure 2). Intravenous abciximab was administered and aggressive, sequential dilatation of the stent was performed using a 4.0 mm noncompliant balloon. Repeat IVUS demonstrated good stent expansion, with thrombus remaining in the distal vessel (Figure 3).

Discussion
       Despite anecdotal reports, recent meta-analyses demonstrate no significant difference in the rate of stent thrombosis in DES compared with BMS.^6–8 These findings are corroborated by studies examining the functional correlates of stent thrombosis, namely the hard clinical endpoints of death and myocardial infarction.¹ However, many of the early trials had restrictive inclusion criteria: only stable patients with non-complex lesions were eligible. In “real-world” practice, DES have often been used in “off-label” indications to treat more complex lesions.
       A recent “real-world” prospective cohort study of 2,229 consecutive patients observed a stent thrombosis rate of 1.3% 9 months after implantation of DES. Twenty-seven percent of these patients were diabetic, and 79% of the lesions were characterized as complex.⁴ This study identified a number of independent predictors of stent thrombosis, including premature discontinuation of antiplatelet therapy, bifurcation lesions, diabetes mellitus, renal impairment and low ejection fraction. However, the majority of these factors are not specific to DES. The most significant factor was premature discontinuation of antiplatelet therapy (hazard ratio: 89). This result was consistent with another prospective study of 652 patients who received DES: premature discontinuation of antiplatelet drugs was associated with a 30-fold increased risk of stent thrombosis.⁹ In this study, 25% of patients who discontinued clopidogrel experienced stent thrombosis. Although many of the risk factors for stent thrombosis apply to both BMS and DES, with premature discontinuation of antiplatelet therapy, the hazard of stent thrombosis may be greater with DES compared with BMS.
       Mechanical factors have also been demonstrated to contribute to stent thrombosis. In addition to lesion complexity,⁴ increasing stented length is also significantly associated with stent thrombosis.⁸ As stent length increases, full deployment becomes less likely. In a prospective IVUS-based study of 12 patients with stent thrombosis following BMS implantation, severe underexpansion was found in all patients.¹⁰ A case-control study of 15 patients with stent thrombosis after implantation of DES demonstrated significantly reduced cross-sectional area and stent underexpansion in the stent thrombosis group.¹¹ Underexpansion has also been shown to underlie failed treatment of in-stent restenosis (ISR): an IVUS follow-up study identified underexpansion in 9 of 11 cases of recurrence after DES implantation for ISR.12
       The predictive utility of IVUS in stent thrombosis was demonstrated in a study of 53 patients who underwent stent implantation under IVUS guidance and subsequently suffered stent thrombosis. Ninety-four percent had at least 1 prior abnormality on IVUS, whereas angiographic abnormalities were detected only in 32%.¹³ As well as identifying stent underexpansion, IVUS is also useful in guiding subsequent management. In a study of 15 patients with ISR, initial deployment of DES was associated with underexpansion in 66% on IVUS, despite predilatation and the use of cutting balloons.¹⁴ However, following high-pressure postdilatation, there was a significant increase in luminal dimensions on IVUS and a doubling in the proportion of patients with optimal stent deployment.
       Historically, IVUS was available in a minority of high-volume cardiac centers. Expertise was further limited by poor image quality and low spatial resolution. Improved catheter technology and higher spatial resolution have enhanced its utility, and reduction in costs has made IVUS a practical proposition for both low- and high-volume centers.

Conclusion
       Stent thrombosis is a rare but serious complication which can occur with DES or BMS. Despite early anecdotal reports, meta-analyses have not found any significant difference in the rate of stent thrombosis in DES compared with BMS if antiplatelet therapy is used appropriately. Several independent predictors of stent thrombosis have been identified, and stent underexpansion is likely to play a key role. In “real-world” practice, DES are frequently used in more complex and technically demanding situations, and in these circumstances, the importance of adequate deployment must not be underestimated.
       The achievement of adequate stent expansion and vessel wall apposition is crucial to minimize ISR and stent thrombosis, regardless of the nature of the stent. We suggest that the use of IVUS is essential in the management of acute stent thrombosis to identify stent underdeployment and guide subsequent management.

1. Hill RA, Dundar Y, Bakhai A, et al. Drug-eluting stents: An early systematic review to inform policy. Eur Heart J 2004;25:902–919.
2. Orford JL, Lennon R, Melby S, et al. Frequency and correlates of coronary stent thrombosis in the modern era: Analysis of a single center registry. J Am Coll Cardiol 2002;40:1567–1572.
3. Cutlip DE, Baim DS, Ho KK, et al. Stent thrombosis in the modern era: A pooled analysis of multicenter coronary stent clinical trials. Circulation 2001;103:1967–1971.
4. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126–2130.
5. McFadden EP, Stabile E, Regar E, et al. Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet 2004;364:1519–1521.
6. Bavry AA, Kumbhani DJ, Helton TJ, et al. Risk of thrombosis with the use of sirolimus eluting stents for percutaneous coronary intervention (from registry and clinical trial data). Am J Cardiol 2005;95:1469–1472.
7. Bavry AA, Kumbhani DJ, Helton TJ, et al. What is the risk of stent thrombosis associated with the use of paclitaxel-eluting stents for percutaneous coronary intervention?: A meta-analysis. J Am Coll Cardiol 2005;45:941–946.
8. Moreno R, Fernandez C, Hernandez R, et al. Drug-eluting stent thrombosis: Results from a pooled analysis including 10 randomized studies. J Am Coll Cardiol 2005;45:954–959.
9. Jeremias A, Sylvia B, Bridges J, et al. Stent thrombosis after successful sirolimus eluting stent implantation. Circulation 2004;109:1930–1932.
10. Alfonso F, Suarez A, Angiolillo DJ, et al. Findings of intravascular ultrasound during acute stent thrombosis. Heart 2004;90:1455–1459.
11. Fujii K, Carlier SG, Mintz GS, et al. Stent underexpansion and residual reference segment stenosis are related to stent thrombosis after sirolimus-eluting stent implantation: An intravascular ultrasound study. J Am Coll Cardiol 2005;45:995–998.
12. Fujii K, Mintz GS, Kobayashi Y, et al. Contribution of stent underexpansion to recurrence after sirolimus-eluting stent implantation for in-stent restenosis. Circulation 2004;109:1085–1088.
13. Uren NG, Schwarzacher SP, Metz JA, et al. Predictors and outcomes of stent thrombosis: An intravascular ultrasound registry. Eur Heart J 2002;23:124–132.
14. Blackman DJ, Porto I, Shirodaria C, et al. Usefulness of high-pressure post-dilatation to optimize deployment of drug-eluting stents for the treatment of diffuse in-stent coronary restenosis. Am J Cardiol 2004;94:922–925.