Journal of Cardiology (2009) 54, 470—474

CASE REPORT

Two cases of acute coronary syndrome thatoccurred by preoperative discontinuation ofantiplatelet therapy in the chronic phaseafter stent implantation

Hajime Fujimoto (MD) ∗, Rieko Ishimura (MD), Susumu Tao (MD),Sachiko Ito (MD), Yo Fujimoto (MD), Sugao Ishiwata (MD, FJCC),Tetsu Yamaguchi (MD, FJCC), Minoru Ohno (MD, FJCC)

Department of Cardiovascular Center, Toranomon Hospital, 2-2-2 Toranomon,Minato-ku, Tokyo 105-8470, Japan

Received 7 September 2008; received in revised form 16 January 2009; accepted 12 February 2009Available online 20 March 2009

KEYWORDSStent;Thrombosis;Platelet inhibitors;Coronary artery disease

Summary After stent implantation in the coronary arteries, patients sometimeshave to undergo invasive examination or treatments that mandate discontinuation ofantiplatelet therapy for several days. We encountered two cases of acute coronarysyndrome that occurred after preoperative discontinuation of antiplatelet agents inthe chronic phase after stent implantation. In the first case, antiplatelet agents weretemporarily stopped 5 months after the implantation of a bare metal stent (BMS)in preparation for a kidney transplant. In the second case, antiplatelet agents werestopped 1.5 months after BMS implantation in preparation for esophageal bypasssurgery. In both cases, acute myocardial infarction occurred just after the invasive

operation, despite the fact that they had continued dual antiplatelet therapy for theperiod recommended by the American Heart Association/American College of Cardi-ology guideline. This report provides a warning about the temporary discontinuationof antiplatelet agents even in the chronic stage of coronary stent implantation.

ge of

© 2009 Japanese Collereserved.

After stent implantation in the coronary arteries,the patients sometimes have to undergo inva-sive examination or treatment. In such cases, the

∗ Corresponding author. Tel.: +81 3 3588 1111;fax: +81 3 3582 7068.

E-mail address: hafujimotoc-circ@umin.ac.jp (H. Fujimoto).

psaoaTo

0914-5087/$ — see front matter © 2009 Japanese College of Cardiolodoi:10.1016/j.jjcc.2009.02.009

Cardiology. Published by Elsevier Ireland Ltd. All rights

atients must stop taking antiplatelet agents foreveral days before the invasive procedure. Therere many reports about in-stent thromboses that

ccurred after discontinuation of antiplatelet ther-py within a few months of stent implantation [1,2].he American Heart Association/American Collegef Cardiology (AHA/ACC) guideline recommends

gy. Published by Elsevier Ireland Ltd. All rights reserved.

ACS at the chronic phase of stent implantation 471

Figure 1 Angiographic findings of Case 1. (A) Coronary angiography (CAG) revealed a severe stenosis in the mid-portionof the left anterior descending artery (LAD). (B) A Liberte stent (2.75 mm × 24 mm) was successfully implanted in theLAD on May 25, 2007. (C) Final angiogram of Liberte stent implantation. (D) CAG was performed on October 24, 2007.T lloonm ulari

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he picture shows thrombosis in the Liberte stent. (E) Baax. 10 atm). (F) Final angiogram of target lesion revasc

hat patients should be treated with clopidogrelnd aspirin for 1 month after BMS implantation, 3onths after sirolimus-eluting stent implantation,months after paclitaxel-eluting stent implanta-

ion, and ideally, up to 12 months if possible, inrder to provide continued protection for in-stenthrombosis [3]. The U.S. Food Drug and Admin-stration recommends adherence to the labelingor use of stents to avoid in-stent thrombosis.owever, it is unclear how long dual antiplateletherapy should be continued before the patientsafely stop antiplatelet agents. Here we report twoases of acute coronary syndrome that occurredfter preoperative discontinuation of antiplateletherapy following stent implantation. In both ofhe cases reported here, the patients had beendministered dual antiplatelet agents for at leasts long as recommended by the AHA/ACC guide-ine, but stent thrombosis occurred during theiscontinuation of antiplatelet therapy in the peri-

perative period. This report will alert physicianshat preoperative discontinuation of antiplateletherapy may be a risk for acute coronary syndromeven in the chronic stage after stent implanta-ion.

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angioplasty was performed (Voyager, 2.75 mm × 20 mm,zation.

ase reports

ase 1

51-year-old man was admitted to our hospi-al to undergo kidney transplantation in October007. He had a past history of diabetic nephropa-hy, and had started to undergo hemodialysis ineptember 2006. He was admitted to our hospital tondergo kidney transplantation on April 24, 2007.tress thalium scintigraphy performed on April 27evealed stress-induced ischemia in the antero-eptal area of the heart. Coronary angiographyevealed severe stenosis in the mid-portion of theeft anterior descending artery (Fig. 1A). He under-ent percutaneous coronary intervention (PCI) onay 25, 2007. A bare metal stent (Liberte stent,.75 mm × 24 mm) was implanted in the stenoticesion (Fig. 1B and C). Dual antiplatelet therapysing 100 mg of aspirin and 200 mg of ticlopidineer day was started and he was discharged from the

ospital on May 30. The patient was subsequentlyeadmitted to the hospital for kidney transplanta-ion on October 10. Aspirin and ticlopidine wereiscontinued and intravenous administration of

472 H. Fujimoto et al.

Figure 2 Angiographic findings of Case 2. (A) Coronary angiography (CAG) was performed in June 2008. There was asevere stenosis in the mid-portion of the right coronary artery (RCA). (B) A Driver stent (3.5 mm × 18 mm) was implantedin the RCA on July 2. (C) Final angiogram at percutaneous coronary intervention showed adequate dilatation of the

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stent. (D) Acute myocardial infarction occurred on Septethe Driver stent. (E) After thrombectomy and balloon dilastent (3.5 mm × 15 mm) was successfully implanted in therevascularization.

heparin at a dose of 400—600 units/h was startedon October 11, keeping the activated partial throm-boplastin time (APTT) between 40 and 60 s. OnOctober 23, oral administration of beta-blocker(5 mg of bisoprolol per day) was stopped. On Octo-ber 24, he underwent kidney transplantation. In themorning of the next day, he complained of chestcompression. The time from discontinuation of hep-arin to the onset of chest compression was 18 h.An electrocardiogram (ECG) showed ST elevationin leads V1—V5. He underwent emergent coronaryangiography, which showed definite thrombosisaccording to the Academic Research Consortium(ARC) definitions in the existing Liberte stent(Fig. 1D). Red thrombus was collected by thrombec-tomy followed by successful balloon angioplasty(Voyager, 2.75 mm × 20 mm, max. 10 atm, Fig. 1E).Peak serum creatine kinase was 1200 IU/ml (16 hafter the onset). There were no other major com-plications and the patient was discharged from thehospital on December 9.

Case 2

A 66-year-old man was admitted to our hospitalwith the diagnosis of carcinoma of the esopha-

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r 3. CAG showed thrombosis at the proximal portion ofn (Marverick, 3.75 mm × 20 mm, 12 atm), another Driverombosed lesion. (F) Final angiogram of the target lesion

us on June 15, 2007. Stress scintigraphy revealedtress-induced ischemia in the inferior wall. Henderwent coronary angiography (CAG) on June0. CAG showed severe stenosis in the mid-ortion of the right coronary artery (RCA). Hetarted dual antiplatelet therapy (100 mg of aspirinnd 200 mg of ticlopidine per day), and under-ent PCI on July 2. A bare metal stent (Driver

tent, 3.5 mm × 18 mm) was successfully implantedFig. 2A—C). Aspirin and ticlopidine were discon-inued and intravenous administration of heparint a dose of 500—700 units/h was started on August2, 2007, keeping APTT between 40 and 60 s. Oraldministration of beta-blocker (60 mg of meto-rolol) was stopped on August 18. He underwentsophageal bypass surgery on August 19, 2007. Hep-rin was restarted on August 22. However, beforeestarting the antiplatelet and beta-blocker ther-py, on September 2, he complained of chestain and an ECG revealed ST elevation in leadsI, III, and aVF. He underwent emergent CAGn suspicion of acute myocardial infarction. CAG

howed definite thrombosis in the stent accordingo the ARC definitions (Fig. 2D). Red thrombus wasollected by thrombectomy followed by balloonilatation and the implantation of another Driver

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tent (3.5 mm × 15 mm, Fig. 2E and F). Serum cre-tine kinase rose to 1626 IU/ml 18 h after the onsetf myocardial infarction.

iscussion

ere we report two cases of acute coronaryyndrome that occurred after preoperative discon-inuation of antiplatelet therapy in the chronichase of stent implantation. There are no clearuidelines and definitive strategy for the treatmentf patients who undergo stent implantation andave to discontinue antiplatelet therapy in prepa-ation for an invasive treatment. According to theHA/ACC recommendation, in order to prevent in-tent thrombosis after coronary stent implantation,atients should be treated with clopidogrel andspirin for at least 1 month after BMS implanta-ion [3]. These are based on the anticipated timet takes for the stent struts to become adequatelyndothelialized. In the cases presented here, acuteoronary syndrome occurred because of discontin-ation of dual antiplatelet therapy; in Case 1 aftermonths and in Case 2 after 1.5 months. Based on

hese findings, care should be exercised when dis-ontinuing antiplatelet therapy even in the chronichase after stent implantation.

Thus far, several risk factors of in-stent throm-osis have been reported, morphological androcedural factors such as long stents, small ves-els, and suboptimal stent results, as well as clinicalactors such as advanced age, renal failure, dia-etes, and the use of immunosuppressive agentshat may promote endothelial dysfunction [4—8]. Inase 1, several factors such as relatively small stent2.75 mm in diameter), renal failure, diabetes, andmmunosuppressive agents might have contributedo the in-stent thrombosis. However, in Case 2,here seems to be no additional risk factors otherhan discontinuation of antiplatelet therapy. So wehould reconsider the period of dual antiplateletherapy after stent implantation, and take moreare to avoid in-stent thrombosis even if the patienteems to have little risk for in-stent thrombosis.

Several pathological mechanisms of stent throm-osis have been reported [9]. In the two casesf our report, there is a possibility that plaqueupture occurred at the proximal portion of thetents, or there had been a plaque prolapse attent struts, inducing stent thrombosis. It was

lso reported that thrombosis is closely related tohe hyper-inflammatory state [10—12]. In both ofur cases, inflammatory reaction might have beenvoked at the stent sites by stopping aspirin. Anti-nflammatory drugs such as statins might be useful

473

n such cases [13]. In any case, discontinuation ofntiplatelet drugs might have been the most crucialrigger for stent thrombosis.

According to another AHA/ACC advisory regard-ng the discontinuation of dual antiplatelet therapyn patients with coronary artery stents [14], implan-ation of BMS or balloon angioplasty should beonsidered in patients who are undergoing prepa-ation for PCI and are likely to require invasive orurgical procedures within the next 12 months. Inoth cases reported here, it might have been bet-er to perform as a first treatment option PCI byalloon angioplasty only.

The AHA/ACC advisory described above alsotates that aspirin should be continued if possi-le for patients treated with coronary stents whore to undergo subsequent procedures that man-ate discontinuation of thienopyridine therapy, andhat thienopyridine should be restarted as soon asossible after the procedure [14]. In these twoases, it might have been better to perform kidneyransplantation and esophageal bypass surgery withontinuing aspirin if at all possible, or consider these of other antiplatelets that have shorter half-ife-time such as cilostazol and beraprost, etc. untilfew days before the surgical procedure.The AHA/ACC guideline also recommends periop-

rative beta-blocker therapy for patients with riskf coronary artery disease [15]. Beta-blocker ther-py had been discontinued for 1 day in Case 1, and4 days in Case 2 when stent thrombosis occurred.iscontinuation of the beta-blocker might also haveontributed to the in-stent thrombosis. Administra-ion of intravenous beta-blocker may be effectiveo prevent stent thrombosis when the patient can-ot take oral therapy.

In conclusion, we encountered two cases ofcute coronary syndrome that occurred after pre-perative discontinuation of antiplatelet therapy inhe chronic phase of stent implantation. This reportrovides a warning about the temporary discontin-ation of antiplatelet therapy in the chronic statef coronary stent implantation.

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