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Letter: Safety and Efficacy Issues of Tirofiban Use in Endovascular Procedures: What Are the Actual Indications?

To the Editor: We have read with great interest the article, “A New Protocol for Anticoagulation With Tirofiban During Flow Diversion” by Chalouhi et al. Although the authors are to be commended for their research about new drug protocols to prevent thromboembolic events during endovascular procedures, we have some terminological and methodological concerns to report. First, we believe that the term anticoagulation is widely used throughout the article in amisleading way. As a matter of fact, no new protocol for anticoagulation is actually used because the heparin dosage reported is largely widespread in most centers: the novelty introduced by the authors is about the use of tirofiban. It is of paramount importance because it helps to better clarify drug activities and regimes, to distinguish antiplatelet or antiaggregation activity from anticoagulation. Tirofiban is an antiplatelet agent and its effect relies on the inhibition of the aggregation process, which subsequently leads to the activation of the actual coagulation cascade or secondary hemostasis. We believe that care must be taken in the use of the correct terminology to avoid confusion in describing the growing plethora of experimental drugs used in the field of thrombosis and hemostasis. Our second concern is about the conclusions that have been drawn from this study. Although the authors honestly outlined the limitations of this study, they have also stated that their protocol has optimal safety and practical characteristics, thus making it a desirable alternative to prophylactic aspirin and clopidogrel loading during the use of flow-diverter stents. In our opinion, this is at least still questionable. The protocol reported by the authors implies that a tirofiban administration of 0.1 mg per kilogram per minute is started immediately after a flow-diverter stent deployment and continued for the next 2 hours after the procedure. Because tirofiban's half-life range varies from 2 to 4 hours, it is acceptable to say that any prospective benefit that could arise from its use should be evident in the first few hours. Comparing the data from this study with the most extensive analogous series in literature, which was performed before the use of tirofiban, we have the chance to trace the differences in the incidence of complications by time of onset and by aneurysm location. Chalouhi et al report a global 4.9% of complication in the anterior circulation. In particular, the hemorrhage rate is 2.4% in the first 96 hours (1 of 41). In the same aneurysm localizations during the first 72 hours, Kallmes et al reported intracranial hemorrhage and ischemic stroke rates of 0.4% (3 of 703) and 2.1% (15 of 703), respectively, for a combined 2.5% rate. Clearly, the series presented does not allow us to draw any statistically sound conclusion. We cannot infer that tirofiban may increase the risk of early rebleeding, but what is more important is that nothing certain can be said about its prospective efficacy in ischemic stroke prevention. Relevantly, the same group reported in a previous publication that the increase in hemorrhagic events triggered by the use of a different tirofiban protocol during endovascular procedures led them to finally turn it into the current protocol. We surely believe that a fast-acting drug like tirofiban, which has a short half-life and no evidence of poor responders is appealing, especially in emergency or unexpected settings when antiaggregation is needed. On the basis of the currently available data in the literature, however, not only do we not know whether tirofiban has more (if any) efficacy on preventing ischemic issues, but we are not even sure whether the suggested tirofiban protocol turns out to be detrimental in comparison with the standard aspirin plus clopidogrel loading. Before endorsing the use of a prophylactic use of glycoprotein IIb/ IIIa inhibitors in the practical use, randomized trials are urgently needed to better evaluate the correct balance between their efficacy and safety. At the moment, we believe that glycoprotein IIb/IIIa inhibitors should be used only in the case of intraprocedural problems. CORRESPONDENCE