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Fatal oral anticoagulant‐related intracranial hemorrhage: a systematic review and meta‐analysis
Author(s) -
Katsanos A. H.,
Schellinger P. D.,
Köhrmann M.,
Filippatou A.,
Gurol M. E.,
Caso V.,
Paciaroni M.,
Perren F.,
Alexandrov A. V.,
Tsivgoulis G.
Publication year - 2018
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13742
Subject(s) - medicine , meta analysis , oral anticoagulant , intracranial hemorrhages , intensive care medicine , anticoagulant , subarachnoid hemorrhage , anesthesia , surgery , warfarin , atrial fibrillation
Background and purpose Intracranial hemorrhage ( ICH ) is the most feared complication in patients treated with oral anticoagulants due to non‐valvular atrial fibrillation. Non‐vitamin K oral anticoagulants ( NOAC s) reduce the risk of ICH compared with vitamin K antagonists ( VKA s). We performed a systematic review and meta‐analysis to evaluate the risk of fatal NOAC ‐related ICH compared with VKA ‐related ICH . Methods We calculated the corresponding risk ratios ( RR s) in each included study to express the relative risk of fatal ICH amongst all patients receiving oral anticoagulation with either NOAC s or VKA s. We additionally evaluated the mortality rates in NOAC ‐related ICH in patients treated with and without NOAC ‐specific reversal agents (idarucizumab and factor Xa inhibitors antidote). Case fatality was evaluated at 30–90 days following symptom onset. Results Our literature search identified six eligible studies (four randomized controlled trials and two open‐label trials of NOAC ‐specific reversal agents). In pairwise analyses, NOAC s were found to have a lower risk of fatal ICH compared with VKA s [ RR , 0.46; 95% confidence interval ( CI ), 0.36–0.58] with no heterogeneity ( I 2 = 0%) across included randomized controlled trials. However, the case fatality rate was similar in NOAC ‐related and VKA ‐related ( RR , 1.00; 95% CI , 0.84–1.19) ICH with no evidence of heterogeneity ( I 2 = 0%). In the indirect analysis, the case fatality rate of NOAC ‐related ICH in patients treated with specific reversal agents was lower compared with the remainder of the patients [17% (95% CI , 11–24%) vs. 41% (95% CI , 34–49%); P < 0.001]. Conclusions Non‐vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non‐valvular atrial fibrillation compared with VKA s, whereas indirect comparisons indicate that NOAC ‐specific reversal agents may be associated with a lower case fatality rate in NOAC ‐related ICH .