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Meta-Analysis
. 2023 Mar;8(1):117-124.
doi: 10.1177/23969873221131635. Epub 2022 Oct 29.

Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis

Michele Romoli  1 , Eleonora Matteo  2 , Ludovica Migliaccio  3 , Mauro Gentile  3 , Maria Giulia Mosconi  4 , Giuseppe Maria Scura  4 , Marcello Naccarato  5 , Enrico Colangeli  6 , Paolo Candelaresi  7 , Vincenzo Andreone  7 , Fabrizio Giammello  8 , Rosa Fortunata Musolino  8 , Cristina Dell'Aera  8 , Federica Nicoletta Sepe  9 , Edoardo Pronello  9 , Leonardo Barbarini  10 , Marcella Caggiula  10 , Federica Rizzo  11 , Marco Petruzzellis  11 , Elisa Giorli  12 , Maria Luisa Zedde  13 , Sabrina Anticoli  14 , Marilena Mangiardi  14 , Mario Muto  15 , Francesco Diana  16 , Maria Vittoria De Angelis  17 , Anna Digiovanni  17 , Letizia Concari  18 , Sara La Gioia  19 , Maria Sessa  19 , Sara Biguzzi  1 , Francesco Cordici  1 , Marco Longoni  1 , Maria Ruggiero  20 , Silvia Cenciarelli  21 , Paolo Eusebi  22 , Simona Sacco  6 , Valeria Caso  4 , Maurizio Paciaroni  4 , Stefano Ricci  2 , Andrea Zini  3 , Danilo Toni  23 , David Giannandrea  21
Affiliations
Meta-Analysis

Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis

Michele Romoli et al. Eur Stroke J. 2023 Mar.

Abstract

Introduction: Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke.

Patients and methods: We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0-2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups.

Results: Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39-4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12-4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63-3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67-3.50), death (OR = 1.53, 95% CI = 0.73-3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85-7.16).

Discussion and conclusion: People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.

Keywords: Stroke; antidote; direct oral anticoagulants; thrombectomy; thrombolysis.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors have no conflict of interest related to this work. Relevant disclosures outside the submitted work: MP received honoraria from Sanofi-Aventis, Boehringer Ingelheim, Bayer, Bristol Myers Squibb, Daiichi Sankyo, and Pfizer. VC received honoraria from Boehringer Ingelheim, Bayer, and Daiichi Sankyo, and Pfizer. SS reports personal fees and nonfinancial support from Allergan, Abbott, Eli Lilly, Novartis, Teva, Bayer, Pfizer, Medtronic, Starmed, Bristol-Myers Squibb, and Daiichi Sankyo. SR reports nonfinancial support from Bayer. AZ declares consulting fees from Boehringer-Ingelheim, Alexion and CLS Behring, and declares grant from the Italian Ministry of Health as principal investigator for clinical trial (RF-2019-12370834). DT reports fees for advisory board and speaker honoraria from Abbott, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, and Pfizer. All other authors have nothing to declare.

Figures

Figure 1.
Figure 1.
Pooled risk estimate for symptomatic intracranial hemorrhage (sICH), good functional outcome and death for dabigatran reversal versus control group.
See this image and copyright information in PMC

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