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Short-term ε-aminocaproic acid treatment and endovascular coil embolization

TO THE EDITOR: We read with interest the article by Malekpour and colleagues6 (Malekpour M, Kulwin C, Bohnstedt BN, et al: Effect of short-term ε-aminocaproic acid treatment on patients undergoing endovascular coil embolization following aneurysmal subarachnoid hemorrhage. J Neurosurg [epub ahead of print June 17, 2016; DOI: 10.3171/2016.4.JNS152951]), describing short-term treatment with ε-aminocaproic acid (EACA) in a consecutive case-control cohort undergoing endovascular treatment. The authors found no reduction in the risk of pretreatment recurrent bleeding in the EACA treatment group. Furthermore, short-term treatment showed no increase in pulmonary embolism and deep venous thrombosis (DVT), either in the risk of vasospasm, clinical stroke, or radiological infarction. This article is important: it is one of the few reports describing short-term EACA treatment before endovascular aneurysm occlusion. Interestingly, the authors found no increase in the risk of DVT, which is in contrast to the findings of Foreman et al.2 and Starke et al.7 This is especially remarkable because the authors continued EACA treatment until the start of the endovascular procedure, which is in contrast with previous reports in which EACA treatment was discontinued several hours before endovascular aneurysm treatment5,7 because of the potential risk of more thromboembolic complications during aneurysm treatment. Some points that might have strengthened the study are data on the total average dose of administered EACA, the mean duration of administration of EACA, and whether EACA treatment led to more risk of thromboembolic complications during aneurysm treatment. Furthermore, the authors report that short-term treatment resulted in no increase in the risk of vasospasm, clinical stroke, or radiological infarction. However, a clear definition of vasospasm and clinical stroke was not provided, nor were how and when radiological infarction was defined and which modality was used. Hence, interpretation of these results remains difficult. It is remarkable that the recurrent bleeding percentage was low when compared to findings reported in the literature: 3.1% versus 4.1% in the no treatment versus EACA treatment group, respectively. The authors report some factors that might have led to these low percentages: first, a decrease in the time interval between aneurysm rupture and treatment over the years; and second, interhospital transfers of some patients. A recent study by Germans et al.3 did indeed show that early recurrent bleeding occurs in 12% of individuals, with an additional 4% of patients having possible recurrent bleeding. Also, Germans et al.3 found that up to 40% of patients had recurrent bleeding before reaching a treatment center. Therefore it might be possible that out-of-hospital recurrent bleeding and that occurring during interhospital transfer was underreported. Nevertheless, Germans et al.3 found that the median time from onset of hemorrhage to recurrent bleeding was only 3 hours, precluding a positive effect of even more expeditious treatment. Therefore, it appears that the start of antifibrinolytic treatment as early as possible is warranted, preferably as soon as the diagnosis of subarachnoid hemorrhage (SAH) is made, and only for a very short period of time, up until the causative aneurysm is treated. In this way the beneficial effects on recurrent bleeding are maximized, and the side effects of long-term treatment are minimized, as proposed in the recent update on the use of tranexamic acid in patients with SAH.1 An ongoing, randomized, controlled trial (the UltraEarly Tranexamic Acid After Subarachnoid Hemorrhage [ULTRA] trial) is currently enrolling patients in the Netherlands,4 and is registered at the Dutch Trial Registry (NTR3272) and clinicaltrials.gov (NCT02684812). This study should provide an answer to the question of whether ultraearly (as soon as possible after diagnosis) and shortterm (until aneurysm treatment—with a maximum of 24 hours) tranexamic acid treatment leads to a better functional outcome. The final results are expected in 2019.