Facilitated Percutaneous Intervention
Following Combination Therapy with Reteplase and Abciximab for Acute Myocardial Infarcti

Case Report. R.C. is a 45-year-old white male who presented to the Emergency Department at Largo Medical Center with a massive acute anterior wall myocardial infarction (MI). The patient denied any prior history of coronary artery disease (CAD), but admitted to intermittent chest pain over the preceding week. He had a moderately severe episode of chest pain lasting nearly 2 hours the evening before this event but the symptoms resolved spontaneously and he attributed the symptoms to indigestion. He was previously treated by his primary care physician with statin therapy for “mild” hyperlipidemia but self-discontinued that medication. The patient had a very strong family history of premature CAD with all male family members sustaining MI prior to age 52, including the patient’s father who had a MI at age 45. The patient was a non-smoker and had no history of hypertension or diabetes. On the day of admission, the patient was kayaking with his family and did not note any exertional symptoms of angina. While resting afterwards, he developed severe mid-sternal chest pain. Symptoms including chest pain, dyspnea, bilateral arm pain, diaphoresis, and nausea beginning at approximately 8:00 am. The patient informed his wife of the symptoms and requested she drive him to the hospital, which was more than 1 hour away. He arrived in the ER at 10:06 am with continued symptoms. He was quickly triaged based on his clinical presentation and a stat EKG demonstrated extensive ST elevation consistent with acute anterior wall MI (Figure 1). The patient received aspirin, nitroglycerin 10 ug/minute IV, a bolus of heparin (80 u/kg) IV, and Lopressor 5 mg IV. Following these treatments, the patient’s blood pressure was 110/60 and pulse was 59/minute; his symptoms lessened in severity but did not entirely resolve. Cardiovascular exam showed no jugular venous distention, a regular cardiac rhythm without any gallop or murmur, clear lungs, and no peripheral edema. Distal extremities were warm and well perfused with easily palpable pulses. After telephone consultation with the cardiologist, the ER physician initiated combination therapy in preparation for immediate facilitated percutaneous intervention in this clearly high-risk patient. The weekend on-call cardiac catheterization laboratory team was notified and arrived in approximately 30 minutes. The patient was screened for contraindications to fibrinolytic therapy or glycoprotein (GP) IIb/IIIa inhibitor therapy and was found to have no contraindications. He was treated with abciximab 0.25 mg/kg IV followed by initiation of a continuous infusion of 0.125 mcg/kg/minute. Reteplase 5 u IV bolus was administered immediately with a second dose of 5 u IV bolus given 30 minutes later. Shortly after the second dose of reteplase, the patient was transported to the cardiac catheterization laboratory at 11:28 am. Diagnostic angiography was performed via a right femoral arterial approach. The left main coronary artery was normal. The left anterior descending artery (LAD) had a severe, flow-limiting 95% stenosis at the level of the first septal perforator. There was TIMI-2 flow gradually filling the LAD which had an additional mid-vessel stenosis of 75% (Figure 2). A large first diagonal branch originating distal to the septal perforator had a 70% ostial stenosis. The left circumflex artery (LCx) was non-dominant and provided a single bifurcating obtuse marginal branch. The LCx had a 75% very proximal stenosis followed shortly by a 50% stenosis. The right coronary artery (RCA) was a large, normal vessel with unremarkable posterior descending and postero-lateral branches. ACT was 242 seconds. In view of the angiographic severity and slow flow in the LAD, the decision was made to proceed with immediate intervention. The interventional system included a 6 French XB3-5 guiding catheter, and a Choice PT extra-support exchange-length guidewire. The proximal LAD culprit stenosis was directly stented using a Cordis BX Velocity 3.0/18 mm stent (Figure 3). This stent was deployed with a 14 atmosphere balloon inflation with no residual stenosis. Stent deployment occurred at 11:56 am for a (weekend) “door to balloon” time of 110 minutes. The mid-LAD stenosis was stented as well using a BX Velocity 3.0/13 mm stent with no residual stenosis (Figure 4). Following placement of these two stents, there was no visible thrombus and TIMI-3 flow was noted throughout the LAD (Figure 5). Left ventricular angiography, using a 6 French (Fr) angled pigtail catheter, demonstrated an extensive antero-apical wall motion abnormality with a calculated ejection fraction of 38% in the 30º RAO projection (Figures 6A and 6B). Femoral angiography confirmed the position of the introducer sheath in the right common femoral artery overlying the femoral head. The sheath was removed in the catheterization lab with uncomplicated placement of a 6 Fr Angioseal vascular closure device. No further IV heparin was administered. The abciximab infusion was continued for 12 hours. The patient was loaded with clopidogrel 300 mg orally and then started on a 30-day course of clopidogrel 75 mg daily, in addition to aspirin (325 mg qd), metoprolol (25 mg bid), lisinopril (5 mg bid) and pravastatin (20 mg qhs). The patient’s clinical course was uncomplicated, despite a peak CPK of over 7,000 IU. There was no ventricular or other arrhythmia and the patient had no signs or symptoms of congestive heart failure. The patient ambulated without further anginal symptoms and was stable for discharge 4 days later with plans for elective re-admission for circumflex and diagonal branch intervention in order to achieve complete revascularization. He was readmitted 3 weeks later and underwent LAD/diagonal branch bifurcation stenting as well as ostial LCx stenting. The ventriculogram was repeated at the time of the second catheterization. The antero-apical wall motion abnormality was less extensive with a calculated ejection fraction which was improved from 38% to 45% without mitral regurgitation. The patient subsequently had a non-ischemic treadmill stress test exercising for 7 minutes, with 50 seconds using the Bruce protocol. After completing a course of cardiac rehabilitation, the patient returned to work and has resumed a full level of activity and exercise. Discussion. Optimal treatment of acute MI continues to evolve. Early approaches focused on administration of fibrinolytic agents due to the advantage of nearly universal availability and ease of administration. Third generation fibrinolytic agents such as reteplase and tenecteplase have been molecularly engineered in an effort to improve safety, ease of administration, rapidity of reperfusion, and clinical outcomes. Despite these advances, a mortality floor of approximately 6–7% has been noted in the large scale fibrinolytic trials (GUSTO-I1, GUSTO-III2, ASSENT-23). Angiographic studies have shown some improvement in restoration of normal TIMI-3 coronary flow but even this surrogate endpoint is reached in only approximately 60% of patients. An alternative to fibrinolytic therapy is direct percutaneous intervention. Studies with angioplasty and stenting have shown significantly higher TIMI-3 flow rates in excess of 90% but with similar or perhaps slightly lower (3–4%) mortality rates (PAMI4, PAMI-Stent5). This apparent superiority of acute percutaneous intervention compared to fibrinolytic therapy for acute MI is offset by several limitations. Only approximately 20% of U.S. hospitals possess interventional cardiac catheterization laboratories and a highly trained cardiology staff capable of successfully and safely performing intervention for acute MI. A further limitation is the nearly universal delay involved in transporting a critically ill patient from the ER to the cath lab. The “door to balloon” time in most institutions averages 90–120 minutes. Many physicians remain reluctant to choose an interventional approach to acute MI due to these delays in treatment. Adjunctive pharmacologic therapy for acute MI intervention is a complex issue. There are abundant data showing that results of acute MI intervention are improved considerably with the use of GP IIb/IIIa inhibitors (RAPPORT6, STOP-AMI7, ADMIRAL8), yet the safety of such agents used immediately following fibrinolytic therapy is not only not established, but is unstudied. Thus, ER physicians and cardiologists are often left with the choice of delaying therapy while awaiting transfer to the interventional setting, or administering fibrinolytic therapy prior to intervention knowing that a GP IIb/IIIa inhibitor can now no longer be added safely to the pharmacologic regimen, thereby putting the interventionalist at a disadvantage. Although a GP IIb/IIIa inhibitor may be administered in the ER, the vessel patency rate in patients with acute MI with these agents alone is only in the 25–30% range. Restoring culprit vessel patency prior to catheterization is important, since success rates for acute MI intervention are better in patients who arrive in the catheterization laboratory with a patent culprit artery. The efficacy, safety and feasibility of therapy combining a fibrinolytic agent with a GP IIb/IIIa inhibitor have been studied in 2 recently reported studies. The GUSTO-V9 study evaluated half-dose reteplase (5u + 5u) with full-dose abciximab versus standard reteplase monotherapy (10u + 10u). The ASSENT-310 study compared reduced dose tenecteplase combined with full-dose abciximab to standard dose tenecteplase with very low dose heparin with a third study arm evaluating tenecteplase administered with enoxaparin. Both studies employed lower than usual weight-adjusted heparin regimens. Although the GUSTO-V combination therapy protocol did not reduce mortality, it did meet the prespecified mortality endpoint of non-inferiority. Furthermore, there was a significant reduction in multiple secondary endpoints including recurrent MI (2.3% vs. 3.5%; p Facilitated Percutaneous Intervention Following Combination Therapy with Reteplase and Abciximab for Acute Myocardial Infarction Learning objectives. After reading this article and answering the questions, the following objective should be met: 1) provide a historical overview of the treatment approach to acute myocardial infarction; 2) discuss the emerging approaches to patient management of acute myocardial infarction with the use of fibrinolytics; and 3) summarize key clinical data as it relates to fibrinolytics in acute myocardial infarction. QUESTIONS: 1–10 1. Third generation fibrinolytic agents have emerged in an effort to improve: a. Safety b. Ease of administration c. Rapidity of reperfusion d. Clinical outcomes e. All of the above 2. Angiographic studies have shown improvement in restoration of normal TIMI-3 coronary flow in what percentage of patients: a. 40% b. 50% c. 60% d. 70% e. 80% 3. Angioplasty and stenting have shown TIMI-3 flow rates of what percent: a. 60% b. 70% c. 80% d. 90% e. 100% 4. What percentage of U.S. hospitals possess interventional cardiac catheterization laboratories: a. 20% b. 30% c. 40% d. 50% e. 60% 5. The “door to balloon” time in most institutions is: a. 60–90 minutes b. 60–120 minutes c. 90–150 minutes d. 120–150 minutes e. 90–120 minutes 6. The efficacy, safety, and feasibility of therapy combining a fibrinolytic agent with a glycoprotein (GP) IIb/IIIa inhibitor have been studied in which 2 recently reported studies: a. PAMI & GUSTO-III b. RAPPORT & ADMIRAL c. GUSTO-V & ASSENT-2 d. ASSENT-3 & GUSTO-V e. ASSENT-3 & GUSTO-III 7. In ASSENT-3, which of the following were the pharmacological study arms: a. Reduced dose tenecteplase combined with full-dose abciximab b. Standard dose tenecteplase combined with very low dose heparin c. Tenecteplase administered with enoxaparin d. a, b, & c e. a & b 8. In the SPEED study, what percentage of the PCI group obtained combined TIMI-2/3 flow: a. 96.7% b. 97.6% c. 91.7% d. 97.1% e. 96.1% 9. The ideal treatment for acute MI is one that would combine the rapidity and ease of administration of fibrinolytic therapy with: a. High final culprit vessel patency b. Activity against “white” clots and “red” clots c. Low mortality d. Low recurrent ischemic event rate e. All of the above 10. Which 2 treatment arms will be prospectively studied in the upcoming FINESSE trial? a. Combination therapy followed by intervention vs. emergent intervention with heparin and a GP IIb/IIIa inhibitor b. GP IIb/IIIa inhibitor combined with fibrinolytic therapy vs. PCI c. GP IIb/IIIa inhibitor combined with fibrinolytic therapy vs. emergent intervention with heparin d. Emergent intervention with heparin and a GP IIb/IIIa inhibitor vs. emergent intervention e. Third generation fibrinolytic vs. intervention Learning Asssessment: Successful completion entails completing the entire evaluation form, sending it to the correct address listed below, and scoring at least 70% on the learning assessment. Certificates will be mailed to those who successfully complete the learning assessment by February 31, 2003. All tests and evaluations must be received by February 31, 2003. Fax this completed form to (610) 560-0501 or mail it to: Trish Levy, CME Director HMP Communications 83 General Warren Blvd., Suite 100 Malvern, PA 19355 Evaluation and Registration Information: (Please Include the following information) Your Name Degree Position/Title Your Organization/Institute Department Your Mailing Address for Certificate (Home or work): Street Address City State Zip Code Email Address Social Security Number Phone ( ) Fax ( ) Answers (Refer to learning assessment) Circle one letter for each answer: 1. A) B) C) D) E) 2. A) B) C) D) E) 3. A) B) C) D) E) 4. A) B) C) D) E) 5. A) B) C) D) E) 6. A) B) C) D) E) 7. A) B) C) D) E) 8. A) B) C) D) E) 9. A) B) C) D) E) 10. A) B) C) D) E) Evaluation (circle one) Excellent (4) Good (3) Satisfactory (2) Poor (1) Accuracy and timeliness of content: 4 3 2 1 Relevance to your daily practice: 4 3 2 1 Impact on your professional effectiveness: 4 3 2 1 Relevance of the content to the learning objectives: 4 3 2 1 Effectiveness of the teaching/learning methods: 4 3 2 1 Avoided commercial bias or influence 4 3 2 1 Evaluation, Part 2: Now that you have read this article, can you: (circle one) 1) Provide a historical overview of the treatment approach to acute myocardial infarction? Yes No 2) Discuss the emerging approaches to patient management of acute MI with the use of fibrinolytics? Yes No 3) Summarize key clinical data related to the use of fibrinolytics in acute myocardial infarction? Yes No What questions do you still have? How will you use what you have learned from this activity? All tests must be received by February 31, 2003. Thank you for your participation.

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