Cardiovascular Revascularization Medicine 11 (2010) 264.e13–264.e15

Fibrinolytic therapy for very late stent thrombosis—is it a viable option?

Abdul Hakeem⁎, Sabha Bhatti, Imran Arif, Mohamed Effat, Mehmet Cilingiroglu

Division of Cardiovascular Diseases, College of Medicine, University of Cincinnati, Cincinnati, OH, USA

Received 4 October 2009; received in revised form 16 November 2009; accepted 20 November 2009

Abstract Stent thrombosis (ST) has a very high case fatality and morbidity rates. The risk of very late ST is

⁎ Corresponding a231 Albert Sabin WCincinnati, OH 45252216640.

E-mail address: ah

1553-8389/09/$ – seedoi:10.1016/j.carrev.2

significantly increased with drug-eluting stents (DES) compared to bare-metal stents for at least up to4 years. Discontinuation of clopidogrel therapy is the single most important consistently identifiedrisk factor. Immediate reperfusion, preferably by primary percutaneous coronary intervention (PCI),has been considered the therapy of choice. Compared to de novo ST-elevation myocardial infarction(STEMI), myocardial infarction (MI) related to ST has significantly higher major adversecardiovascular events (MACE) and lower reperfusion rates. Due to the significantly higher mortalityassociated with STEMI due to ST, prompt revascularization assumes paramount significance. Ourcase reflects the potential utility of fibrinolytic therapy for STEMI due to very late ST. Systemicfibrinolysis should be considered for ST in the presence of ongoing significant ischemia andunavailability of prompt PCI.© 2010 Elsevier Inc. All rights reserved.

Keywords: Late Stent thrombosis; Fibrinolysis

1. Case summary

A 57-year-old male with past medical history of coronaryartery disease, status post two DES implantations (sirolimus-eluting stent, 3.0×18 and 3.0×15 mm) to the right coronaryartery (RCA) 4 years ago and hyperlipidemia, wastransferred from an outside facility with an inferior wallST-segment elevation myocardial infarction (STEMI). Thepatient underwent a routine screening colonoscopy earlierthat day. Five days ago, he was taken off aspirin andclopidogrel as a routine measure precolonoscopy. Thepatient denied any recent exertional symptoms and hadbeen in his usual state of health. He had a normal stress testseveral months ago. He had an unremarkable colonoscopyand no biopsies were taken. During recovery from theanesthesia, the patient started experiencing chest pain withpressure radiating to his shoulders associated with some

uthor. College of Medicine, University of Cincinnati,ay, Academic Health Center, PO Box 670542,7-0542, USA. Tel.: +1 6086953048; fax: +1 513

akeem@gmail.com (A. Hakeem).

front matter © 2010 Elsevier Inc. All rights reserved.009.11.007

shortness of breath. He had no nausea, vomiting butappeared pale and diaphoretic. He was immediatelytransferred to the emergency room where a 12-lead EKGshowed normal sinus rhythm with acute ST-segmentelevations in leads II, III, and aVF with reciprocal changesin leads I and AVL, V1 through V3. Due to bad weather, hecould not be medflighted and the nearest mobile intensivecare unit was at least 60 min away. It was hence decided toproceed with fibrinolytic therapy after all contraindicationswere excluded. The patient was given 10 U of reteplase over2 min followed by another 10 U at 30 min apart. Followingreteplase, his chest pain resolved and there was nearcomplete resolution of ST elevation at 90 min. The patientstayed hemodynamically and electrically stable throughout.He was then transferred to our university hospital for furthermanagement. A transthoracic echocardiogram was donewhich showed a left ventricular ejection fraction of 50% withmoderate hypokinesis of the inferior myocardium.

A coronary angiogram showed normal left main coronaryartery and nonobstructive disease in the left anteriordescending and circumflex arteries. RCA was a very largedominant vessel with a patent stent in the distal segment andTIMI 3 flow throughout the vessel. The mid RCA had a

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patent stent, but just proximal to this stent there was a 40–50% stenosis (Fig. 1). Left ventricular angiogram showed anejection fraction of 55–60%. The left ventricular end-diastolic pressure was 15 mmHg. The inferobasal and midinferior walls were hypokinetic.

The patient was started on optimal medical therapyincluding dual antiplatelets (ASA 325 mg qid and clopido-grel 75 mg qid), beta-blocker, ACE inhibitor, and statin. Hedid remarkably well throughout the hospitalization withoutany adverse events and was discharged 3 days later. Thepatient was seen 3 weeks later in the clinic and he was totallyasymptomatic. He underwent an exercise treadmill test andhe walked for N9 min without any symptoms.

2. Comment

Very late ST (N1 year) has emerged as a well-recognizedcomplication of DES. In observational studies, the risk oflate stent thrombosis (LST) continues to be reported at aconstant rate (0.6%/year; significantly higher with DES) upto at least 4 years after stenting [1]. It is now wellestablished that delayed healing (i.e., lack of completeendothelialization) is the primary pathologic substrateunderlying these events and that N50% of stent struts inhumans are not covered by the endothelium up to 24 monthsafter DES placement [2,3]. DES thrombosis leads tocomplete vessel occlusion with a high thrombus burden.The inciting event and pathophysiology are distinct fromplaque rupture and ensuing thrombosis. However, the finalcommon pathway is the same, i.e., thrombosis. Itsoccurrence is expected to increase with the number ofstent—in particular (DES)—implantation procedures doneworldwide. Clinical consequences of ST are generallycatastrophic, including short-term mortality rates of up to20% to 25% and major myocardial infarction (MI) in 60%to 70% of cases and 6-month mortality rates, amongsurvivors of ST, of up to 20% to 25% [4,5]. The

Fig. 1. Patent stent in mid-dist

presentation of ST is very often a STEMI [6,7]. Repeatpercutaneous coronary intervention (PCI) is the commonlyadopted treatment in the ST setting. However, few scientificdata are available on procedural and midterm comparison ofSTEMI due to ST vs. de novo STEMI.

Chechi et al. [8] compared outcomes and proceduralsuccess rates from 92 patients with STEMI due to ST with 98patients with de novo STEMI. All patients underwentprimary PCI. Patients with ST had a lower likelihood ofsuccessful reperfusion (odds ratio 6.8, P=.004), higher distalembolization rates, and higher rates of in-hospital majoradverse cardiovascular events (MACE). Patients in the STgroup had a higher in-hospital MACE rate (25.6% vs. 9.2%,P=.003), with higher mortality, reinfarction, and targetvessel revascularization rates but not stroke rate, which wassimilar between the two groups (17.4% vs. 7.1%, P=.03;8.1% vs. 1%, P=.02; 9.3% vs. 2%, P=.009; 0% vs. 1%,P=.3, respectively).

Primary PCI is considered the therapy of choice forSTEMI. There are, however, numerous limitations withlogistics being the major one. It is now well established thatin patients with total ischemic time (from onset of chest pain)b1 h, fibrinolytic therapy has the same success rate andclinical outcomes as compared to PCI [9]. The absolute riskreduction in death, reinfarction, and stroke conferred byprimary PCI over fibrinolysis is lost if the PCI-related timedelay (door-to-balloon time−door-to-needle time) is N1 h.Hence when a substantial delay in initiating primary PCI isanticipated, reperfusion therapy with fibrinolytic agentsshould be strongly considered [9,10]. This would be all themore important in the setting of an ST given the several-foldhigher adverse outcome rates.

One important issue pertains to establishing the precisediagnosis of ST, especially late and very late ST. Diagnosinglate or very late ST may be particularly challenging as eventscould occur secondary to restenosis and target lesionrevascularization, especially if an additional or different

al RCA with good flow.

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stent is implanted at that time [4]. Given this challenge, theAcademic Research Consortium (ARC) has formulatedconsensus definitions for DES study end points [11].Accordingly, ST is defined as definite (confirmation ofthrombus either at angiography, autopsy, or thrombectomy),probable (any MI that is related to documented acuteischemia in the territory of the implanted stent withoutangiographic confirmation of ST and in the absence of anyother obvious cause), or possible (clinical definition ofpossible ST is considered to have occurred with anyunexplained death from 30 days after intracoronary stentinguntil end of trial follow-up). Our patient met the criteria forboth definite and probable ST per ARC criteria. Moreover,the ARC recommends the combination of adjudicateddefinite and probable ST to best characterize very late ST.It should be noted that the ARC definitions require evidenceof a clinical event and do not include silent late occlusions asmanifestations of ST.

Sciahbasi et al. [12] recently reported four cases ofsuccessful fibrinolytic therapy for ST. All cases had a veryshort symptom-to-treatment time (b50 min). Bowater et al.[13] also presented a case of successful thrombolysis withtenecteplast and adjunctive glycoprotein IIb/IIIa inhibitor forsubacute ST. Similarly, our patient received fibrinolytictherapy within 30 min of onset of chest pain and had nearcomplete ST-segment resolution at 90 min.

Taken together, these cases demonstrate the feasibility,safety, and efficacy of fibrinolytic therapy for LST withoutthe need for further mechanical intervention. It is veryimportant to appreciate that success (immediate and long-term) of fibrinolytic therapy is largely contingent onsymptom-to-treatment time.

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