Abciximab Bolus Injection Does Not Reduce Cerebral Ischemic Complications of Elective Carotid Artery Stenting
A Randomized Study
Background and Purpose— Abciximab has been shown to significantly reduce thromboembolic complications of coronary artery stenting. A prospective, randomized study was performed to test whether abciximab has comparable beneficial effects in carotid artery stenting.
Methods— Seventy-four consecutive patients undergoing elective stenting of the carotid artery were included in the study. Standard antithrombotic medication consisted of aspirin, clopidogrel, and heparin. In addition, half of the patients received an abciximab bolus of 0.25 mg/kg body weight given prophylactically before the intervention.
Results— The procedure was successful in all but 1 patient. In patients receiving abciximab, ischemic complications consisted of 4 transient ischemic attacks, 1 minor stroke, 1 nonfatal major stroke, and 1 fatal stroke caused by cerebral hemorrhage. In the control group, 2 transient ischemic attacks and 1 major nonfatal stroke occurred. In summary, the total number of periprocedural ischemic events was 7 (19%) in the abciximab group and 3 (8%) in the control group. Nonischemic complications consisted of 1 inguinal hematoma requiring blood transfusions in each group.
Conclusions— Abciximab bolus given prophylactically before elective carotid artery stenting does not reduce ischemic complications.
Carotid artery stenting has become an alternative method of treatment in patients with significant carotid artery stenosis.1,2⇓ The most important complication of the procedure consists of acute ischemic events, most likely resulting from cerebral embolism. Accepted adjuvant antithrombotic medical therapy to overcome this problem consists of aspirin combined with ticlopidine or clopidogrel. Abciximab, a glycoprotein IIb/IIIa antagonist, has been shown to reduce ischemic complications in percutaneous coronary interventions. In carotid artery stenting, however, the drug has not been given prophylactically in a randomized trial; therefore, its role is unclear. We conducted a randomized, prospective study to elucidate the value of abciximab bolus in addition to established antithrombotic therapy in patients undergoing elective carotid artery stenting.
Materials and Methods
Seventy-four consecutive patients undergoing elective stenting of the carotid artery were included in the study. The indication for the procedure was ≥80% stenosis of the extracranial carotid artery in asymptomatic patients or ≥60% stenosis in symptomatic patients. Baseline demographic characteristics are listed in Table 1. Exclusion criteria according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) protocol3 were present in 23 patients (31%). Premedication consisted of aspirin (100 mg/d) and clopidogrel (75 mg/d) starting 2 days before intervention. After vascular access was obtained, a bolus of 5000 U IV heparin-sodium was given. Immediately thereafter, patients were randomized by use of sealed envelopes to an abciximab group and a control group. The protocol of the study consisted of abciximab 0.25 mg/kg body weight IV in the abciximab group. Patients in the control group did not receive abciximab except in case of a cerebral ischemic event, which finally occurred in 3 patients. Another patient randomized to the control group received abciximab on the decision of the operator because of a visible dissection of the intima outside the implanted stent and the need to implant a second stent. In 1 patient in the control group, abciximab was given because of an emerging problem in a coronary vessel treated in the same session. All 5 patients in the control group who finally received an abciximab bolus were counted in the control group for statistical calculations on an intention-to-treat basis. In 1 patient in the abciximab group, the drug was not given because of an evolving hematoma at the puncture site, which was treated conservatively.
At least 2 projections of the carotid artery stenosis were obtained for calculation of vessel diameter and degree of stenosis. Stenosis diameter was determined according to the NASCET criteria with the distal internal carotid artery serving as the reference segment (Table 2). The calculation was performed with a semiautomatic device (Hicor, Siemens). Two experienced cardiologists using commercially available balloons and stents performed carotid artery stenting. A description of the principles of our technique has been published elsewhere.4 In summary, stenting was performed with a percutaneous transfemoral access. An 8F modified cerebral guiding catheter (Cordis) was placed in the common carotid artery just proximal to the segment to be treated. The stenosis was passed by an extra support coronary guidewire (Stabilizer, Cordis). After predilation with a 4- or 5-mm balloon that was 20 mm long, a self-mounted slotted-tube stent (Palmaz-Schatz, Jo-Stent) was deployed with high-pressure inflations (12 to 16 atm). In the last 24 consecutive patients, primary stenting without predilation was performed (Table 3). The ratio of stent balloon to artery diameter was ≈1.1: 1. Vascular sheaths were removed after 4 to 6 hours.
Neurological events were classified according to Wholey et al.5 A transient ischemic attack was classified as any neurological deficit that resolved within 24 hours and left no evidence of residual neurological damage. A minor stroke was classified as a new neurological event that resulted in slight impairment of neurological function that either completely resolved within 7 days or caused an increase in National Institute of Health (NIH) stroke scale of <4.6 A new neurological deficit that persisted after 7 days and increased the NIH stroke scale score by ≥4 was classified as major stroke.6 Ischemic events were assessed in all patients by neurological examination before and the day after intervention by a neurologist who was not aware of the patient’s treatment group. All patients were examined 30 days after the procedure by the neurologist; until this point in time, no additional neurological adverse events occurred.
Written, informed consent was obtained from each patient, and the study was approved by our institutional review board.
All values are expressed as mean±SD. Differences between both groups are compared by use of Student’s t test and the χ2 test. A value of P≤0.05 was considered significant. Data were analyzed on an intention-to-treat basis.
The intervention was successful in all but 1 patient, defined as a minimal residual stenosis of <20% after stenting (Table 3). In 1 patient in the abciximab group, access to the carotid artery was not possible because of severe angulation of the vessel. Nonischemic complications consisted of the necessity of blood transfusions as a result of inguinal hematoma in 1 patient in each group.
Ischemic complications consisted of 6 transitoric ischemic attacks, 1 minor stroke, and 2 major strokes, all occurring within 24 hours of the intervention (Table 4). After a major stroke, an 84-year-old man subsequently died during hospital stay. Autopsy confirmed an intracerebral hemorrhage as the underlying pathology. Although there was a trend toward more ischemic events in the abciximab group, the difference was not statistically significant. Within 30 days of the intervention and during the follow-up of a mean of 17±8 months, no further neurological events were observed.
Abciximab has been shown to reduce ischemic complications in percutaneous coronary interventions. The effects were more consistent in patients who experienced unstable angina.7–10⇓⇓⇓ In a small, placebo-controlled study, abciximab was used in patients with recent stroke.11 Abciximab showed minimal improvement in clinical outcome with no complications exceeding placebo. In another case report, thrombotic complications during angioplasty of cerebral arteries could be successfully treated with abciximab.12,13⇓
According to these promising results, abciximab was used in several small, uncontrolled studies in patients undergoing carotid artery stenting.14–16⇓⇓ Chastain et al16 used abciximab in 23 high-risk patients prophylactically or intraprocedurally as a bailout therapy. The study did not include a control group. Qureshi et al15 administered abciximab only prophylactically in 20 high-risk procedures involving not only the carotid arteries but also the vertebral and basilar arteries. Stents were not used in all patients. Both series showed promising results; however, because of the lack of control groups, the potential benefit of the drug could not be defined.
In our study, bolus injection of abciximab was not followed by an infusion for 12 hours. The rationale for this protocol was that cerebral embolism complicating carotid artery stenting usually occurs intraprocedurally, making an infusion for 12 to 24 hours following the intervention of no further value. However, giving an abciximab infusion for several hours was thought to increase the likelihood of intracerebral bleeding.
In our randomized study, abciximab did not diminish the procedural complication rate. Several factors could contribute to this finding: First, the components of the atherosclerotic plaque in carotid arteries differ from that usually found in coronary vessels. The presence or intraprocedural formation of thrombi does not play the same role as it does in coronary arteries.17 There are several clinical studies confirming intraprocedural thrombus formation as a major source of complication during coronary artery stenting.18 During carotid artery stenting, experimental models and clinical studies proved distal embolization of predominantly atherosclerotic debris and calcified material as the main cause of cerebral ischemic complications.19,20⇓ Second, the brain seems to be much more susceptible to bleeding complications than the heart, which explains the increased abciximab-related bleeding rates in carotid stenting compared with coronary stenting. Third, the risk of stent thrombosis increases with smaller stent diameters.21 The mean vessel diameter of carotid arteries is much larger than the diameter of coronary arteries. This means that the potential benefit of abciximab inhibiting clot formation is less pronounced in carotid arteries compared with coronary arteries. The question of whether plaque stabilization by abciximab provides any additional benefit for weeks after the intervention is not influenced by the present study because no delayed ischemic events occurred in either group.
The main limitation of the study is the relatively small number of patients compared with the multicenter trials investigating abciximab in the setting of coronary artery disease. To exclude harm from abciximab therapy in the setting presented, 150 patients in each group would have been necessary to achieve a test power of 80%.
- Received September 27, 2001.
- Revision received November 20, 2001.
- Accepted December 11, 2001.
- ↵Roubin GS, New G, Iyer SS, Vitek JJ, Al-Mubarak N, Liu MW, Yadav J, Gomez C, Kuntz RE. Immediate and late clinical outcomes of carotid artery stenting in patients with symptomatic and asymptomatic carotid artery stenosis: a 5-year prospective analysis. Circulation. 2001; 103: 532–537.
- ↵Mathias K, Jaeger H, Gissler M. Carotid angioplasty and stent placement: a 20-years experience.In: Henry M, Amor M, eds. Ninth International Course Book of Peripheral Vascular Interventions. Paris, France; 1998:591–599.
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- ↵Brott T, Adams HP, Olinger CP, Marler JR, Barsan WG, Biller J, Spliker J, Holleran R, Eberle E, Hertzberg V, Rorick M, Moomaw CJ, Walker M. Measurement of acute cerebral infarction: a clinical examination scale. Stroke. 1989; 20: 864–870.
- ↵Abciximab in Ischemic Stroke Investigators. Abciximab in Acute Ischemic Stroke: a randomized, double-blind, placebo-controlled, dose-escalation study. Stroke. 2000; 31: 601–609.
- ↵Wallace RC, Furlan AJ, Moliterno DJ, Stevens GHJ, Masaryk TJ, Perl J.II Basilar artery rethrombosis: successful treatment with platelet glycoprotein IIb/SUB-IIIa receptor inhibitor. Am J Neuroradiol. 1997; 18: 1257–1260.
- ↵Tong FC, Cloft HJ, Joseph GJ, Samuels OB, Dion JE. Abciximab rescue in acute carotid stent thrombosis. Am J Neuroradiol. 2000; 21: 1750–1752.
- ↵Cecena FA, Hoelzinger DH, Miller JA, Abu-Shakra S. The platelet IIb/IIIa inhibitor abciximab as adjunctive therapy in carotid stenting of potential thrombotic lesions. J Interv Cardiol. 1999; 12: 355–362.
- ↵Chastain HDII, Mt Wong P, Mathur A, Levine RL, Al-Mubarak NA, Iyer SS, Gomez CR, Vitek JJ. Does abciximab reduce complications of cerebral vascular stenting in high risk lesions? Circulation. 1997; 96: I-283.Abstract.
- ↵White CJ, Ramee SR, Collins TJ, Escobar AE, Karsan A, Shaw D, Jain SP, Bass TA, Heuser RR, Teirstein PS, Bonan R, Walter PD, Smalling RW. Coronary thrombi increase PTCA risk: angioscopy as a clinical tool. Circulation. 1996; 93: 253–258.
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- ↵Cutlip DE, Baim DS, Ho KKL, Popma JJ, Lansky AJ, Cohen DJ, Carrozza JP, Chauhan MS, Rodriguez O, Kuntz RE. Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials. Circulation. 2001; 103: 1967–1971.