Asian Cardiovasc Thorac Ann 2001;9:31-35
© 2001 Asia Publishing EXchange Pte Ltd
Abciximab During Rescue Angioplasty After Failed Thrombolysis
Upendra Kaul, MD,
Rakesh Sapra, MD,
Balbir Singh, MD,
Dinesh Sudan, MD,
Tapan Ghose, MD,
Narayan Shyamsunder Dixit, FRCP,
Harbans Singh Wasir, MD
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Department of Interventional Cardiology Batra Hospital & Medical Research Centre New Delhi, India
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For reprint information contact: Upendra Kaul, MD Tel: 91 11 609 1887 Fax: 91 11 644 3434 email: ukaul{at}del3.vsnl.net.in Department of Interventional Cardiology, Batra Hospital & Medical Research Centre, 1 Tughlakabad Institutional Area, Mehrauli Badarpur Road, New Delhi 110062, India.
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Abstract
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Abciximab (a glycoprotein IIb/IIIa inhibitor) was assessed in 16 of 36 patients with acute myocardial infarction who were referred for rescue angioplasty after failed thrombolysis. Baseline clinical and angiographic characteristics were comparable in the abciximab and non-abciximab groups. Coronary stenting was carried out in all patients in the non-abciximab group and in 13 in the abciximab group. Angiographic success was achieved in all patients. Persistence of slow flow was encountered more frequently in the non-abciximab group (30% versus 6.25%, p < 0.05). Stent thrombosis occurred in 2 patients (10%) who were successfully redilated and there was one case of bleeding requiring transfusion in the non-abciximab group; neither of these complications occurred in the abciximab group. Predischarge left ventricular ejection fraction was better in the abciximab group (44% ± 3% versus 36% ± 3%, p < 0.01). All patients were discharged alive and were asymptomatic at the one-month follow-up. Use of abciximab during angioplasty after failed thrombolysis improved angiographic and clinical results without increasing the risk of bleeding, and reduced the incidence of in-hospital complications. Larger studies are warranted to confirm this important observation.
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Introduction
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Failure of thrombolysis to achieve reperfusion in acute myocardial infarction (AMI) is associated with higher mortality.1 Rescue percutaneous transluminal coronary angioplasty (PTCA) in these patients, although not shown to reduce mortality, seems to be beneficial by improving left ventricular function.2–8 However, arteries in which thrombolysis fails may be associated with a deeper and larger plaque fissure and an increased thrombus burden.9 PTCA in this exceptionally thrombogenic milieu, not surprisingly, has a low angiographic success rate and a high incidence of reocclusion.2–8 Platelets play a crucial role in the formation and extension of thrombi and they are likely to be instrumental in stent thrombosis and occlusion. Platelets have also been implicated in the no-reflow phenomenon that is the predominant cause of lower angiographic success in this setting.10 Therefore, use of an antiplatelet agent is likely to be beneficial by reducing such complications of PTCA. The effect of a very potent antiplatelet drug, the glycoprotein IIb/IIIa inhibitor abciximab (ReoPro; Eli Lilly, Inc., Indianapolis, IN, USA), was assessed during rescue PTCA after failed thrombolysis.
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Patients and Methods
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From June 1997 to December 1999, 36 patients underwent PTCA after failed thrombolysis. Patients in cardiogenic shock were excluded from the study. All enrolled patients had persistence or recurrence of chest pain after throm-bolysis for AMI, with either continuing or recurrent ST-segment elevation in the infarcted territory on electro-cardiography. They were treated on admission with 325 mg of aspirin and 500 mg of ticlopidine before undergoing coronary angiography. At this time, 16 patients were given a bolus injection of abciximab (0.25 mg•kg-1) and started on an infusion of 10 µg•min-1 for 12 hours. The decision to give abciximab was governed by the affordability of this drug to the patient (the cost of the drug being more than the cost of an intracoronary stent) and by the coronary lesion characteristics, especially the presence of a large thrombus, a small vessel (
2.5 mm in diameter), or a bifurcation lesion. Baseline activated clotting time (ACT) was checked in all patients as most were on intravenous heparin or subcutaneous low-molecular-weight heparin on admission. If baseline ACT was < 150 sec, 70 units•kg-1 of heparin was given intravenously at the beginning of the procedure; if baseline ACT was > 150 sec, 50 units•kg-1 of heparin was given. Further doses of heparin were adjusted to keep ACT > 300 sec in the non-abciximab group and > 200 sec in the abciximab group, as in the EPILOG trial.11
PTCA was performed by the standard technique with floppy guidewires and rapid exchange or over-the-wire balloon catheters. After restoration of flow, the lesion was assessed for stent deployment. No lesion was excluded because of the presence of thrombus before or after PTCA. There was no predetermined choice of stent; a variety of stents were used depending upon the vessel characteristics, availability of stents, and preference of the operator. The stents were deployed at high pressure (> 12 atmospheres). Any persistent dissection was treated with additional stents. An angiographic filling defect consistent with thrombus after stenting was treated with additional PTCA. Intracoronary thrombolysis was not used in any case. Slow-flow or no-reflow phenomena were treated with intracoronary nitroglycerin injection (200 µg) followed by intracoronary diltiazem (250 to 750 µg) with or without intracoronary adenosine (12 to 24 µg) if slow flow persisted. All lesions with a stenosis > 70% either proximal or distal to the AMI-related lesion, which might represent a significant inflow or outflow obstruction, were subjected to balloon angioplasty and stented if the result was suboptimal. After the procedure, the sheath was removed when the ACT fell below 160 sec. Two hours later, patients were started on subcutaneous low-molecular-weight heparin (enoxaparin sodium) at a dose of 1 mg•kg-1 12- hourly for 48 to 72 hours. All patients were treated with oral aspirin 160 mg per day indefinitely and ticlopidine 250 mg twice daily for 4 weeks. Patients were ambulated and discharged when stable. Repeat coronary angiograms and left ventriculograms were performed before discharge in all cases. After discharge, all patients were followed up for one month.
Procedural complications including abrupt closure, persistence of slow flow, stent thrombosis, the need for urgent repeat revascularization by PTCA or bypass surgery, and death were considered to be major adverse clinical events. Excessive bleeding was defined as that requiring blood transfusion. Angiographic success was defined as residual stenosis of less than 30% with TIMI flow 
2 (graded according to the Thrombolysis in Myocardial Infarction trial).12 Clinical success was defined as angiog-raphic success with no in-hospital major adverse clinical events.
Quantitative coronary analysis was performed by the automated edge-detection method that is part of the Philips digital angiography system (Philips Medical Systems, Eindhoven, The Netherlands). Antegrade flow during and after PTCA was assessed according to TIMI flow grading.12 TIMI grade 3 flow was defined as complete opacification of the distal coronary bed by the third cardiac cycle. The slow-flow and no-reflow phenomena were defined as sudden reductions of flow to TIMI grade 2 and TIMI grade 1, respectively.
Continuous variables were expressed as mean ± standard deviation, and qualitative variables as percentages. The Student t test and chi-squared test were used to compare continuous and categorical variables, respectively. Differences were considered statistically significant when the p value was < 0.05.
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Results
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Baseline clinical and angiographic characteristics of the abciximab and non-abciximab groups are shown in Tables 1 and 2
. Age, sex, underlying risk factors, location of AMI, Killip class at presentation, and time since throm-bolysis were comparable in the 2 groups. Use of urokinase was more common in the abciximab group. In 2 patients in the abciximab group, streptokinase was used at the time of AMI and urokinase was used on recurrence of chest pain with ST-segment elevation, before referral for PTCA. Thrombosis and small vessel size were more common in the abciximab group; use of abciximab was considered preferable in such cases if the patient could afford it. Multivessel involvement (2 or more vessels) was slightly more common in the non-abciximab group, although not statistically significant. On admission, PTCA of the AMI-related artery only was carried out; PTCA of other suitable arteries was performed before discharge (in 3 patients in the non-abciximab group, and in 2 in the abciximab group). Coronary stents were used in all patients except 3 in the abciximab group (due to small vessel size in 2, and to a huge ectatic artery of 5.5 mm in diameter in the other). The 40 stents deployed comprised almost all available types: 9 Palmaz-Schatz (Cordis, Miami, FL, USA); 8 NIR (Medinol, Jerusalem, Israel); 8 Multilink (Guidant, Temecula, CA, USA); 5 Pro-Stent (OCCAM, Eindhoven, The Netherlands); 2 Bard-XT (Bard, Billerica, MA, USA); 3 Cross-Flex (Cordis, Miami, FL, USA); 3 AVE-GFX (AVE, Santa Rosa, CA, USA); 1 Cook Stent (Cook, Bloomington, IN, USA); and 1 Freedom Stent (Global Therapeutics, Bloomfield, CO, USA). There was no predominance of any stent type in either group.
In-hospital angiographic and clinical outcome is shown in Table 3. Angiographic success was achieved in all patients. However, persistence of slow flow (TIMI flow grade 2) was encountered more often in the non-abciximab group. Stent thrombosis causing reinfarction was en-countered in 2 patients in the non-abciximab group. In the first patient who had an ulcerated proximal left anterior descending artery lesion, there was recurrence of chest pain with ST-segment elevation 6 hours after the initial PTCA and stenting. Repeat angiography showed thrombosis in the stented segment which was redilated and another stent was deployed successfully. The second patient who underwent successful PTCA and stenting of the left anterior descending coronary artery, developed hematemesis 8 hours after the procedure and required 2 units of blood. Chest pain and ST-segment elevation recurred 10 hours later. He was also found to have stent thrombosis; re-dilation and stenting were performed successfully. Both of these patients had patent arteries with TIMI grade 3 flow at the time of predischarge angiography. All 36 patients were discharged alive and remained free of symptoms at the one-month follow-up.
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Discussion
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Angioplasty after failed thrombolysis has been associated with a low rate of angiographic success and a high rate of reocclusion. Although placement of intracoronary stents during primary angioplasty has been reported to be safe and attributed with a better angiographic outcome, the results of stenting in patients with failed thrombolysis are not clear.13 This population has a high mortality rate and identification of this group is one of the challenges in contemporary cardiology. In such patients, angioplasty has been reported to improve left ventricular function and reduce the incidence of heart failure, however, reduced mortality has not been clearly demonstrated.2–8 This is possibly due to a lower angiographic success rate of 84% and a higher occlusion rate of 18%.8 Although failure of thrombolysis seems to be an unsatisfactory environment for coronary stenting, this study demonstrates that stent placement in this setting is feasible and relatively safe. However, persistence of slow flow was seen frequently and 2 patients developed acute stent thrombosis within 24 hours of the procedure. A possible reason for the high incidence of the slow-flow phenomenon is a large thrombus burden with platelet activation resulting from the thrombolytic therapy, leading to tissue edema, micro-embolization, microvascular plugging, and microvascular spasm.
Recently, abciximab, a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor was shown to be beneficial in high-risk coronary angioplasty and with primary PTCA, in improving in-hospital and long-term outcome.10,14 In addition, the role of abciximab in reversal of the no-reflow and slow-flow phenomena during coronary intervention was also documented.15 Beneficial effects of coronary stenting during rescue PTCA compared to plain balloon PTCA have recently been reported.16 In this study, we observed an additional benefit of abciximab in improving the angiographic result and reducing the incidences of slow-flow and reocclusion. Keeping in mind that baseline clinical and angiographic parameters were similar in the 2 groups, the greater preservation of left ventricular function in the abciximab group was attributed to the drug.
An important concern during PTCA in this setting is the increased risk of bleeding complications because of the use of antiplatelet and anticoagulant drugs in the post-thrombolytic phase. However, we did not encounter bleeding complications in the abciximab group, possibly because of careful adjustment of heparin dosage to maintain a low ACT value during PTCA. Further studies are needed to define the role of abciximab in rescue PTCA and determine the subgroups most likely to benefit from this drug, keeping in mind the additional cost involved in its use.
Presented at the 51st Annual Conference of the Cardiological Society of India, New Delhi, India, December 1–5, 1999.
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Abstract
Introduction
