Intra-Arterial Infusion of a Glycoprotein IIb/IIIa Antagonist for the Treatment of Thromboembolism During Coil Embolization of Intracranial Aneurysm: A Comparison of Abciximab and Tirofiban

Discussion

Thromboembolism is a major complication during all steps of coil embolization because thromboembolisms disrupt blood flow and may cause intimal injuries. Accordingly, the prevention and treatment of thromboembolisms are major issues relevant to the use of coil embolization for cerebral aneurysms. Several agents, such as fibrinolytic drugs, tirofiban, and abciximab, have been used intravenously or intra-arterially to treat thromboembolisms during coil embolization of cerebral aneurysms.^{5,7⇓⇓⇓⇓–12} The general consensus is that fibrinolytic agents should not be used for thrombolysis because they carry a significant risk of cerebral hemorrhage. The use of abciximab for thromboembolism during coil embolization of cerebral aneurysms remains controversial; some studies have reported that it is associated with cerebral hemorrhage and severe thrombocytopenia, whereas others have reported no such relationship.^5,7,8 To reduce or prevent these problems, tirofiban, which is a relatively short-acting and reversible glycoprotein IIb/IIIa receptor inhibitor, has been used with increasing frequency for the treatment of thromboembolisms during the coil embolization of cerebral aneurysms. Although there have been studies conducted for acute coronary syndrome, there have been no comparative studies investigating abciximab and tirofiban infusion for the treatment of thromboembolisms induced by coil embolization of cerebral aneurysms. Although our study was not a randomized, controlled study, our comparison of abciximab and tirofiban provides valuable information regarding the treatment of thromboembolisms that occur during coil embolization of cerebral aneurysms because there was no selection intent between abciximab and tirofiban.

The dosage and method of administration of abciximab or tirofiban for the treatment of thromboembolisms during coil embolization of cerebral aneurysms were entirely based on the standard application of these drugs for acute coronary syndrome. Therefore, the dose and application method of these drugs must be adjusted for acute-onset thromboembolisms, which may occur during coil embolization of cerebral aneurysms. In our study, to avoid procedural complications such as cerebral hemorrhage and to reach a high recanalization rate, we administered these drugs intra-arterially rather than intravenously. Because intra-arterial access is most proximal to the thrombus, a smaller total dose of the drug is expected to be effective, and, as a result, dose-dependent complications such as cerebral hemorrhage may be reduced. Additionally, we did not use a loading infusion of abciximab or tirofiban. Repeated intra-arterial pulsatile injections of small doses (abciximab: 2 mg; tirofiban: 50 μg) of the drugs may be sufficient to resolve a thrombus. In our series, the mean dose of abciximab was 12.2 ± 4.1 mg, which represented approximately 70% of the recommended loading dose of abciximab (loading dose: 0.25 mg/kg) for a 70-kg patient. The minimal dose of abciximab was 10 mg, which exceeds 50% of the recommended loading dose. In comparison with our dose of abciximab, the mean dose of tirofiban was 470 ± 290 μg, which represented approximately 56% of the recommended loading of tirofiban (loading dose: 0.4 μg/kg/min × 30 minutes) for a 70-kg patient. Six patients were treated with <50% of the recommended loading dose of tirofiban. Even though our data did not provide the weight of the patients, our doses of abciximab and tirofiban may be lower than usual loading doses. Our dose of tirofiban may be relatively lower than that of abciximab, on the basis of usual loading doses of tirofiban and abciximab. Accordingly, regarding cost-effectiveness and safety, the lower dose of tirofiban that was used may be more beneficial.

Our immediate and follow-up recanalization rates for intra-arterial abciximab (72.7%, 100%) and tirofiban (90.9%, 100%) appear to be similar or superior to those reported in previous studies.^{5,7,8,10⇓–12} This result may be related to the fact that these drugs were used to treat freshly formed thrombi, which may be more readily resolved. Therefore, we suggest that a loading dose of abciximab or tirofiban is not necessary for the treatment of thromboembolisms that form during the coil embolization of cerebral aneurysms.

In our series, both abciximab-treated and tirofiban-treated groups showed no hemorrhage in the ruptured cerebral aneurysms. This may be related to the relatively lower doses of abciximab or tirofiban in comparison with the usual doses.

In our study, the immediate recanalization rate of the tirofiban-treated group was superior to that of the abciximab-treated group, but this difference was not statistically significant. The follow-up recanalization rate was 100% in both groups, with no cerebral hemorrhages. Unlike in the treatment of acute coronary syndromes,^2,3 the efficacy and safety of tirofiban may not be inferior to those of abciximab for the treatment of thromboembolisms during coil embolization of cerebral aneurysms. Accordingly, tirofiban, which has a short plasma half-life and is a competitive inhibitor of glycoprotein IIb/IIIa, may be more suitable than abciximab to treat thromboembolisms during coil embolization of cerebral aneurysms. Operations such as decompressive craniectomy or external ventricular drainage are sometimes necessary after coil embolization, especially in cases of ruptured cerebral aneurysms. Therefore, tirofiban is less likely than abciximab to induce operation-related hemorrhagic complications.