Bivalirudin as an Adjunct to Acute Coronary Intervention in
Post-operative Myocardial Infarction

Increasing evidence supports the use of bivalirudin as an adjunct to percutaneous coronary intervention to minimize bleeding complications.^1,2 We describe a patient who developed an acute myocardial infarction one hour following total knee arthroplasty. During emergent percutaneous coronary intervention, bivalirudin was used for anticoagulation with the intent of minimizing bleeding complications. Intervention was successful and he suffered no post-interventional bleeding from the surgical site. In this peri-operative setting, bivalirudin’s short half-life offered a potentially safer alternative to combination heparin and glycoprotein IIb/IIIa inhibitors. Case Report. A 67-year-old white male underwent total arthroplasty of his right knee at an outlying hospital. His past medical history included rheumatoid arthritis, obesity, hyperlipidemia and myocardial infarction two years prior. Post-myocardial infarction, the patient underwent percutaneous coronary intervention with the placement of a 3.5 x 18 mm BX Velocity™ coronary stent (Cordis Corporation, Warren, New Jersey) in his mid-left anterior descending (LAD) coronary artery. At that time, the patient also received an implantable cardioverter-defibrillator for poor left ventricular function and paroxysmal ventricular tachycardia. Diagnostic left heart catheterization with coronary angiography for cardiac clearance two weeks before his surgery revealed a widely patent mid-LAD at the site of the stent, mild plaque of the proximal LAD (Figure 1A), and an ejection fraction of 30%. The right, left main, and circumflex coronary arteries had subcritical plaque. The patient’s home medication included amiodarone 200 mg daily, aspirin 81 mg daily, clopidogrel 75 mg daily, furosemide 40 mg daily, potassium chloride 30 mEq daily, metroprolol 50 mg daily, simvastatin 10 mg daily, and ezetimibe 10 mg daily. Clopidogrel was discontinued 7 days before surgery. Total knee arthroplasty was uncomplicated except for elevated blood pressure for which the patient was given hydralazine. One hour after surgery, the patient developed ST-segment elevation across the precordial leads and an episode of ventricular fibrillation. The implantable cardioverter defibrillator appropriately discharged and restored normal sinus rhythm. Given his post-operative state, he did not receive anticoagulation or thrombolytics. After re-intubation, the patient was transferred to our facility for emergent cardiac catheterization. Upon arrival to the catheterization laboratory, the patient was artificially ventilated. His blood pressure was 80/50 mmHg and he was receiving intravenous dopamine, norepinephrine and dobutamine. Diagnostic catheterization and coronary angiography were performed by standard Judkin’s technique from the left femoral artery. Left ventriculography was not performed. The LAD was completely occluded within the segment of the two-year-old stent (Figure 1B). There were no other changes noted compared to his prior coronary angiogram. The patient was then given an initial 0.75 mg/kg bolus of bivalirudin followed by a 1.75 mg/kg/hour infusion. A 6 French 3.5 mm EBU guide catheter (Medtronic, Inc., Minneapolis, Minnesota) and a ChoICE® Intermediate J tip guidewire (Boston Scientific Corporation, Maple Grove, Minnesota) were used. The guidewire passed easily through the total occlusion and was advanced to the distal LAD. A Voyager™ Rx 3.0 x 15 mm balloon (Guidant Corporation, Santa Clara, California) could not be advanced beyond the intra-stent occlusion site. The guidewire was withdrawn and despite multiple passes with the guidewire distally in the LAD, the balloon could not advance. It appeared that the inability to advance the balloon was due to wire passage behind an incompletely expanded stent strut segment. Intravascular ultrasound (IVUS) was not attempted since we felt that the IVUS catheter would meet the same fate. Finally, the guidewire was advanced into the more central lumen and the balloon could be passed distally through the occluded stent segment to dilate the site of intra-stent occlusion. Four Taxus™ (Boston Scientific Corp.) stents (3.5 x 12 mm, 3 x 24 mm, 3 x 16 mm, 3 x 20 mm) were then deployed in tandem with TIMI grade 3 flow restored without residual obstruction or filling defects observed (Figure 1C). Before leaving the catheterization laboratory, the patient was given clopidogrel 600 mg through the nasogastric tube. The bivalirudin infusion was stopped at the end of the procedure and an intra-aortic balloon pump was inserted. The patient was transferred to the critical care unit in stable condition. Following completion of the procedure, the patient developed runs of paroxysmal ventricular tachycardia and was started on intravenous amiodarone. Dopamine, dobutamine, norepinephrine, and the intra-aortic balloon pump were continued for cardiogenic shock. Aspirin 81 mg daily, clopidogrel 75 mg daily and subcutaneous heparin for DVT prophylaxis were ordered upon admission to the critical care unit. His troponin I peaked one day post-infarction at 201 ng/mL. CPK and MB fraction peaked at 3,950 mg/dL and 402 mg/dL, respectively (relative index = 10%). Over the next 48 hours, he improved and was weaned from dopamine and norepinephrine. On the second day, the intra-aortic balloon pump was removed and he was extubated on day three. Orthopedic consultation confirmed no bleeding complications from his knee arthroplasty site. Echocardiography done on the second hospital day revealed an ejection fraction of 25%, with mid-septal-to-apical and mid-inferolateral-to-apical akinesis. The remainder of the patient’s hospital course was uncomplicated and he was discharged to an extended care facility for rehabilitation 13 days after admission. Discussion. Surgery is a well-recognized risk factor for myocardial infarction. Mangano et al. reported a 27% incidence of post-operative myocardial ischemia in patients with coronary artery disease or at risk for coronary artery disease. Changes consistent with myocardial ischemia were most common in the first 3 days after surgery. The authors further described post-operative myocardial ischemia as clinically silent and difficult to detect.³ The mechanism by which the coagulation system becomes activated after surgery is poorly understood. However, trauma to tissue leads to exposure of tissue factor and a hyperocoagulable state. Thrombus formation is then dependent on a balance between coagulation and fibrinolysis.^4,5 The initial inability to advance a balloon through the occluded stent segment suggests why the acute infarction occurred. An incompletely expanded stent segment may have been the site of platelet aggregation previously suppressed by chronic clopidogrel therapy. Stopping clopidogrel before surgery, coupled with the relative hypercoagulable state induced by surgical trauma may have been the stimulus causing the thrombosis, despite the fact that pre-operative angiography 2 weeks earlier demonstrated an apparently patent LAD. Although there are reports of late stent thrombosis with drug-eluting stents following clopidogrel withdrawal, we felt that the use of the paclitaxel stent with long-term, uninterrupted use of clopidogrel offered the patient the best opportunity for continued patency.⁶ IVUS interrogation after stent placement may have been ideal to assure optimal stent expansion. However, taking the entire clinical situation into account, including procedural time of 3 hours, 740 ml of contrast used, and the precarious clinical state of the patient, we felt that ending the procedure as quickly as possible was in the patient’s best interest once we had obtained full stent expansion by angiography and assured TIMI 3 flow. There are no current guidelines concerning the cessation versus use of clopidogrel before orthopedic surgery. However, in a survey of 90 vascular surgeons in England, the majority of respondents did not stop clopidogrel therapy prior to surgery.⁷ The risk associated with continuing clopidogrel during the peri-operative period of coronary artery bypass grafting is unclear. In a prospective study of 312 consecutive patients who underwent coronary artery bypass grafting, Chu et al. reported increased blood loss and re-operation in patients taking clopidogrel.8 In a similar prospective study of 1,628 CABG patients, Karabulut et al. reported no significant increase in blood loss or transfusion in patients taking clopidogrel.⁹ Given his immediate post-operative state, the use of glycoprotein IIb/IIIa inhibitors in our patient would have likely led to an unacceptable bleeding risk. Orthopedic complications associated with anticoagulation include hematoma, infection, bleeding from the wound, and compartment syndrome.¹⁰ In the REPLACE-2 trial, heparin and glycoprotein IIb/IIa usage tripled the bleeding complication rate at the vascular access site compared to bivalirudin.¹ The TARGET trial, which compared tirofiban to abciximab, reported the percentage of total TIMI bleeding complications for both drugs as 3.7% and 5.0%, respectively.¹¹ The ESPRIT trial, which assessed the efficacy of routine versus bailout of eptifibatide revealed a 3.8% total TIMI bleeding complication rate.¹² The total TIMI bleeding complication rate for bivalirudin in REPLACE-2 was substantially lower than both trials at 1.9%.¹ In all of these trials, the majority of bleeding complications involved the femoral puncture site, which would be analogous to our patient’s surgical wound. Finally, FDA guidelines for eptifibatide, abciximab, and tirofiban list recent surgery as an absolute contraindication for use.^13–15 Orthopedic patients are typically treated with low molecular weight heparin, coumadin, or low-dose unfractionated heparin post-operatively to prevent thrombosis.¹⁶ Clopidogrel, glycoprotein IIb/IIIa inhibitors, and high-dose heparin protocols are not used for post-operative deep vein thrombosis prophylaxis.^17,18 Although anecdotal, this experience using clopidogrel in percutaneous coronary intervention in the immediate post-operative period of orthopedic surgery did not impose an increased risk of bleeding. This case demonstrates the safe and efficacious use of bivalirudin in a patient undergoing emergent percutaneous coronary intervention in an immediate post-operative acute myocardial infarction. The proximity of the surgery to percutaneous coronary intervention placed this patient at high risk for hemorrhagic complications at the operative site. Because of its short half-life, bivalirudin offered a potentially safer alternative to heparin and glycoprotein IIb/IIIa inhibitors in this setting. The REPLACE-2 trial demonstrated fewer overall bleeding complications with bivalirudin and provisional glycoprotein IIb/IIIa inhibitors compared to planned glycoprotein IIb/IIIa inhibition and heparin.¹ Increasing evidence supports the use of bivalirudin alone in the interventional treatment of ST-segment elevation myocardial infarction.19 In our patient, bivalirudin proved to be a safe choice to provide anticoagulation while minimizing post-operative hemorrhagic complications. Acknowledgement. We wish to thank Dan Evans, DO, for his review of the manuscript. jgorfinkel@cardiologyinc.com

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