Should antiplatelet therapy be interrupted in drug eluting stent recipients throughout the periendoscopic period? A very late stent thrombosis case report and review of the literature

Abstract

In-stent thrombosis after cessation of antiplatelet medications in patients with drug-eluting stents (DES) is a significant problem in medical practice, particularly in the perioperative period. We report a case of an 87-year-old man with a medical history of hypertension, coronary artery disease and chronic atrophic gastritis. Very late thrombosis of a sirolimus-eluting stent occurred 1207 days after implantation, seven months after discontinuation of clopidogrel, and the interruption of aspirin 13 days in preparation of an elective endoscopic gastrointestinal procedure presented with acute myocardial infarction. The patient was treated with thrombectomy and successfully revascularized with superimposition of two sirolimus-eluting stents. Medications administered in the catheterization laboratory included low molecular weight heparin and nitroglycerin. Flow was defined as grade 2 according to the thrombolysis in myocardial infarction scale. Electrocardiogram after the procedure revealed persistent, but decreased, ST-segment elevation in the anterolateral leads. The patient recovered and was discharged on aspirin and clopidogrel indefinitely. There was no cardiac event during the two year follow-up period. This case underlines the importance of maintaining the balance of thrombosis and bleeding during perioperation of non-cardiac procedure and the possible need for continuation of aspirin therapy during periendoscopic procedures among patients with low bleeding risks who received DES.

1. Introduction

Periendoscopic cessation of antiplatelet therapy by practitioners is common in both routine and emergency procedures; this is sometimes unnecessary and may give rise to life-threatening thrombotic complications in patients receiving coronary drug-eluting stents (DES). We report a case of very late stent thrombosis (VLST) that occurred 1207 days after implantation of multiple DES, seven months after discontinuation of clopidogrel and 13 days after interruption of aspirin for the preparation of an elective gastrointestinal (GI) endoscopy practice resulting in acute myocardial infarction.

2. Case Report

On 27 September 2006, an 87-year-old man presented with a medical history of hypertension, coronary artery disease and chronic atrophic gastritis. Cardiac catheterization revealed two vessel coronary diseases (Figure 1A). After preloading with 300 mg of clopidogrel and 300 mg aspirin (po), two sirolimus-eluting stents (SES, CYPHER SELECT™, Cordis Corp., Johnson & Johnson, Warren, New Jersey, 3.5 × 28 mm proximal and 2.5 × 33 mm distal) were deployed in the left anterior descending (LAD), two SES (CYPHER SELECT™ 3.0 × 18 mm mid and Firebird, MicroPort, Shanghai, China, 2.5 × 18mm distal) were implanted in the left circumflex coronary artery (LCX) (Figure 1 B). The procedure was successful with an excellent angiographic result. Thereafter, the patient was put on aspirin 100 mg and clopidogrel 75 mg daily (os). He remained asymptomatic and discontinued his clopidogrel 31 months after the percutaneous coronary intervention (PCI), continuing only on aspirin, statin and beta blockade. On January 18, 2010, he was advised to stop taking aspirin for the preparation of gastrointestinal (GI) endoscope examination requested by relations of patient due to positive serum tumor marker. Just before the procedure, cardiac CT showed no evidence of in-stent restenosis (Figure 1C and D). Thirteen days after his discontinue of aspirin because of gastric discomfort and avoiding gastric hemorrhage, he experienced severe retrosternal chest pain. An electrocardiogram showed ST-segment elevation of 1 mm to 5 mm in leads V1 through V4 (Figure 2 A). The patient's initial troponin I level of 0.02 ng/mL peaked at 25.97 ng/mL 10 h after his admission to the hospital. Coronary angiography performed 3-h after the onset of heart attack revealed total occlusion in the distal LAD at the site of the CYPHER stent by fresh thrombosis (Figure 1E). Aspiration thrombectomy of the distal LAD was attempted, followed by the placement of two overlapping DES (SES, EXCEL, JW Medical System, Weihai, China, 2.75 × 28 mm proximal and 2.5 × 18 mm distal) just because the appropriate size of bare stents was not available in catheter room at that time (Figure 1 F). Flow was defined as grade ? according to thrombolysis in myocardial infarction (TIMI) scale. Medications administered in the catheterization laboratory included low molecular weight heparin and nitroglycerin. Electrocardiogram after the procedure revealed persistent, but decreased, ST-segment elevation in the anterolateral leads (Figure 2 B). The patient recovered and was discharged on aspirin (100 mg/d) and clopidogrel (75 mg/d) indefinitely. There was no cardiac event during the 2-year follow-up period.

Figure 1. Coronary images study.

(A): Baseline coronary angiography in right anterior oblique caudal view showing diffused significant lesions in the proximal and distal segments of the LAD coronary artery (black arrow), and two separate local eccentric lesions with severe stenosis in the middle and distal portion of the LCX (white arrow). (B): Post-procedure coronary angiography in the same view after direct stenting in the same region of LAD (black arrow) and LCX (white arrow). There is no residual stenosis and TIMI 3 flow has been restored in the distal vessel. (C): Coronary and stents morphology visualized by 64-slice MDCT shows patent stents in LAD, with no evidence of restenosis or in-stent thrombus. (D): Curved CT image show patent stents in LCX, with no restenosis and in-stent thrombus. (E): Coronary angiography 38 months after the procedure shows total thrombotic occlusion at the stent site in the distal segment of the LAD (white arrow). (F): The restoration of arterial luminal diameter at the same region of the LAD after the deployment of two drug-eluting stents (white arrows). LAD: left anterior descending; LCX: left circumflex coronary artery; TIMI: thrombolysis in myocardial infarction; MDCT: multidetector computed tomography.

Figure 2. 12-lead electrocardiogram studies after the MI attack.

(A): Electrocardiogram taken 2-h after the onset of chest pain shows ST-segment elevation of 1–4 mm in leads V1 through V5 with hyperacute T waves, consistent with acute anterior-wall MI; (B): Electrocardiogram taken 2-h post PCI shows the ST elevation of chest leads normalized immediately, and proper ST resolution was obtained. MI: myocardial infarction; PCI: percutaneous coronary intervention.

3. Discussion

This case highlights the importance of balancing the interruption of risk/benefit ratio of antiplatelet therapy versus continuation among patients receiving DES during periendoscopic procedures, and the possible need for maintaining antiplatelet medication in high thrombolic risk patients.

Stent thrombosis is a rare but usually a catastrophic complication of stent implantation with high mortality rates of up to 45%.[1] Though dual antiplatelet therapy (DAPT) has markedly reduced the occurrence of stent thrombosis related catastrophic event, the optimal duration of DAPT after DES placement is still unknown. The current guidelines on the optimal duration of DAPT in PCI setting are rather discordant based on the results of studies which are often controversial.[2]^–[5] Cessation of DAPT during the first 6 months after DES implantation, even if temporary, significantly increases the risk of stent thrombosis. Two-thirds of the late DES thromboses are were linked to the discontinuation of antiplatelet drugs.[6] However, the benefit of prolonged DAPT beyond 12 months is not clearly demonstrated.[7]^,[8]

The decision of withdrawing anti-platelet is challenging, particularly among individuals at risk for stent thrombosis, such as those who have atherosclerotic CAD and those who are undergoing PCI. Elective GI procedures per se pose a relatively lower risk for cardiovascular adverse events other than cessation of antiplatelet drugs in high risk patient.[9]^–[16]

However, compared with the high rate of stent thrombosis associated with premature discontinuation of DAPT, the doubled infarction and death rates in ACS and a more difficult emergency PCI for revascularization of a thrombosed coronary vessel, it appears that periendoscopic bleeding is generally less hazardous than thrombosis, and therefore, it is preferable to continue antiplatelet therapy during endoscopy whenever reasonable.

To the best of our knowledge, 1207 days is a relative longer interval between the deployment of a DES and the occurrence of a clinical event that was associated with VLST. Herein, we discuss the case of our patient, review the pertinent medical literature, and reinforce the importance of continuous and uninterrupted aspirin therapy in DES recipients throughout the periendoscopic period, except in circumstances when the risk of bleeding significantly outweighs the benefit of continued anticoagulation.