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Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid
Maud A Tjerkstra1, René Post1, Menno R Germans1
1From the Department of Neurosurgery (M.A.T., R.P., V.V., B.A.C., W.P.V., D.V.), Amsterdam UMC, University of Amsterdam; Department of Neurosurgery (M.R.G.), Clinical Neuroscience Centre, University Hospital Zurich, Switzerland; Department of Neurology and Neurosurgery (M.D.I.V., G.J.E.R.), UMC Utrecht Brain Centre, University Medical Centre Utrecht; Departments of Neurology (K.J.) and Neurosurgery (J.F.C.W.), Haaglanden Medical Centre, Den Haag; Departments of Neurosurgery (R.W.K.) and Neurology (N.D.K.), Leiden University Medical Centre; Departments of Neurosurgery (F.C.B., D.N.) and Intensive Care (H.K.), ISALA Hospital, Zwolle; Departments of Neurosurgery (B.P.) and Neurology (G.R.), Elisabeth Tweesteden Ziekenhuis, Tilburg; Department of Neurology (F.B.), Spaarne Gasthuis, Haarlem; Department of Neurology (L.J.A.R.), Ziekenhuisgroep Twente, Almelo; Department of Neurology (P.J.A.M.B.), Medisch Spectrum Twente, Enschede; Department of Neurology (V.I.H.K.), OLVG, Amsterdam; Department of Neurology (T.C.R.), Dijklander Hospital, Hoorn; Department of Neurology (H.P.B.), Gelre Hospital, Apeldoorn; Department of Neurosurgery (H.D.B.); Department of Neurology, Donders Institute for Brain, Cognition and Behaviour (C.J.M.K.), Radboud University Medical Centre, Nijmegen; Departments of Radiology and Nuclear Medicine (R.B., C.B.L.M.M.), Intensive Care (J.H.), and Neurology (Y.B.W.E.M.R.), Amsterdam UMC, University of Amsterdam., the Netherlands.
Background And Objectives:
The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH.
Methods:
The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade (p = 0.10).
Results:
Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56).
Discussion:
This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care.
Trial Registration Information:
ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013).
Classification Of Evidence:
This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.
