Idarucizumab for dabigatran reversal: A systematic review and meta-analysis of indications and outcomes

Horst, S.F.B. van der; Martens, Emily S.L.; Exter, Paul L. den; Bos, Mettine H.A.; Mens, T.E. van; Huisman, Menno V.; Klok, Frederikus A.

doi:10.1016/j.thromres.2023.05.020

Cited by 8 publications

(3 citation statements)

References 35 publications

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“…ADX, IDA, PCC, and Vit-K are usually administered to address bleeding and prevent a poor prognosis. 1,5,6,13,[16][17][18] Therefore, the present investigation aims to verify the real-world incidence of major bleeding events associated with ongoing anticoagulation and to compare the results of the different reversal or repletion strategies currently available for pharmacological treatment. Because the present study is an analysis of the management of bleeding events in the real world without systematic verification of achievement of hemostatic control, other than through clinical judgment of cessation of bleeding, we chose short-term mortality as a hard endpoint to ensure that cases with adverse outcomes are highlighted depending on the poor effect of the therapy or the presence of comorbidities.…”

Section: Discussionmentioning

confidence: 99%

Reversal or Repletion Treatment Strategies and Outcomes of Patients With Major Bleeding Events Managed in the Emergency Department: Large Real-Life Investigation in the Northwestern Healthcare District of Tuscany

Conti,

Leorin,

Bogazzi

et al. 2024

Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine

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Objective: To verify the incidence of bleeding events in patients on ongoing anticoagulant treatment in the real world and compare the results of different reversal or repletion strategies currently available for pharmacological treatment. Methods: Patients managed in the emergency department (ED) with major bleeding events, on ongoing anticoagulation were stratified according to bleeding site and reversal or repletion therapy with andexanet alfa (ADX), idarucizumab (IDA), prothrombin complex concentrate (PCC), and vitamin K (Vit-K). Endpoint: Death at 30 days was compared in the subgroups with cerebral hemorrhage (CH) and gastrointestinal (GI) bleeding. Results: Of the 809,397 visits in the years 2022–2023 at 6 EDs in the northwestern health district of Tuscany, 5372 patients with bleeding events were considered; 3740 were excluded due to minor bleeding or propensity score matching. Of the remaining 1632 patients with major bleeding, 548 on ongoing anticoagulation were enrolled; 334 received reversal or repletion agents. Patients with CH (n = 176) and GI bleeding (n = 108) represented the primary analysis cohorts in the study’s strategic treatment assessment. Overall, 30-day survival of patients on ongoing aFXa treatment receiving on-label ADX versus off-label PCC showed a relative increase of 71%, while 30-day survival of patients on ongoing aFII receiving on-label IDA versus off-label PCC showed a relative increase of 30%; no substantial difference was found when comparing on-label PCC combined with Vit-K versus off-label Vit-K alone. Indeed, patients undergoing on-label ADX or IDA showed a statistically significant difference over off-label PCC (ADX vs. PCC: n = 15, events = 4, mean ± SD 82.50 ± 18.9, vs. 49, 13, 98.82 ± 27, respectively; analysis of variance [ANOVA] variance 8627; P < 0.001; posthoc test diff 32, 95% confidence interval: 28–35; P < 001; IDA vs. PCC: 20, 5, 32.29 ± 15.0 vs. 2, 1, 28.00 ± 0.0, respectively; ANOVA 1484; P < 0.001; posthoc test −29, −29 −29, respectively; P = n.d.). On-label PCC combined with Vit-K showed overall a slight statistically significant difference versus off-label Vit-K alone (52, 16, 100.58 ± 22.6 vs. 53, 11, 154.62 ± 29.8, respectively; ANOVA 310; P < 0.02; posthoc test 4, 0.7–7.2, respectively; P < 0.02). Data were confirmed in the group of patients with CH (ADX vs. PCC: n = 13, events = 3, mean ± SD 91.55 ± 18.6 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA variance 10,091, F = 261; P < 0.001; posthoc difference test 36, 95% confidence interval: 30–41; P < 0.001; IDA vs. PCC: 10, 2, 4.50 ± 2.5 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA 16,876,303, respectively; P < 0.001; posthoc test 41, 34–47, respectively; P < 0.001). On-label PCC combined with Vit-K showed an overall slight statistically significant difference compared with off-label Vit-K alone (P < 0.01 and P < 0.001 in the subgroups of CH and GI bleeding). Conclusions: Patients undergoing specific reversal therapy with on-label ADX or IDA, when treated with aFXa or aFII anticoagulants, respectively, showed statistically elevated differences in 30-day death compared with off-label repletion therapy with PCC. Overall, 30-day survival of patients on ongoing aFXa or aFII receiving on-label reversal therapy with ADX or IDA compared with off-label PCC repletion agents showed an increase of 71% and 30%, respectively.

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Section: Discussionmentioning

confidence: 99%

Reversal or Repletion Treatment Strategies and Outcomes of Patients With Major Bleeding Events Managed in the Emergency Department: Large Real-Life Investigation in the Northwestern Healthcare District of Tuscany

Conti,

Leorin,

Bogazzi

et al. 2024

Critical Pathways in Cardiology: A Journal of Evidence-Based Medicine

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“…Another study comparing idarucizumab-treated AIS patients who subsequently received IVT to patients treated with IVT with no prior anticoagulation showed better improvement (measured using NIHSS) and better functional outcome (measured using mRS) in the idarucizumab-treated group, with a similar frequency of complications [65]. The incidence of thromboembolic events after idarucizumab uptake also seems to be low -a recent systematic review with meta-analysis including 3,602 patients found it to be 2% [66].…”

Section: Discussionmentioning

confidence: 99%

Reversing dabigatran effect with idarucizumab to enable intravenous thrombolysis in patients with acute ischaemic stroke — a single centre experience

Włodarczyk,

Sawczyńska,

Wrona

et al. 2023

Neurol Neurochir Pol.

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Introduction.Our study analysed the safety and effectiveness of idarucizumab in enabling intravenous thrombolysis (IVT) in dabigatran-treated patients with acute ischaemic stroke (AIS).Clinical rationale for the study. New oral anticoagulants (NOAC), including dabigatran, are the first-choice treatment option for preventing ischaemic stroke in patients with non-valvular atrial fibrillation (AF). However, a significant percentage of AF patients develops AIS despite NOAC treatment. According to current guidelines, treatment with IVT is contraindicated in patients who have received NOAC within the last 48 hours. Idarucizumab is a fragment of a monoclonal antibody that reverses the anticoagulation effect of dabigatran. The latest research shows that it can enable safe and successful IVT in patients with recent dabigatran intake, but more data is needed to confirm the safety and effectiveness of such treatment. Material and methods.Our study included dabigatran-treated patients who received idarucizumab to allow AIS treatment with IVT in the University Hospital in Kraków (Poland) from December 2018 to June 2023. We gathered data on their past medical history, stroke severity, course of treatment and outcomes as defined by modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) scores at discharge. A good functional outcome was defined as mRS 0-2 points at discharge. Results. This observational study included 19 patients (13 male and six female) with a median age of 74 (IQR = 13) years. In all patients (100%), the reason for dabigatran treatment was AF. A good functional outcome after treatment (mRS 0-2) was achieved in 68.4% of patients, but mRS was already ≥ 3 points before stroke onset in three (15.8%) patients. Haemorrhagic transformation of stroke occurred in three (15.8%) patients, including symptomatic intracranial haemorrhage in two (10.5%). The mortality rate was 5.3%. Conclusions and clinical implications.Our study results are in line with previous research on this topic, showing that IVT after idarucizumab can be successfully administered and is reasonably safe in dabigatran-treated patients with AIS.

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“…Reversal agents include idarucizumab for dabigatran and andexanet alfa for rivaroxaban and apixaban [ 27 , 36 ]. The unfavorable side of these reversal agents is their exceptionally high price and the lack of availability in all centers.…”

Section: Discussionmentioning

confidence: 99%

Plasma Drug Values of DOACs in Patients Presenting with Gastrointestinal Bleeding: A Prospective Observational Study

Bozic,

Alicic,

Martinovic

et al. 2023

Medicina

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Background and Objectives: Anticoagulants are a well-known risk factor for gastrointestinal bleeding (GIB). In recent years, direct oral anticoagulants (DOACs) have taken a leading role in the treatment and prevention of thromboembolic incidents. The aim of this study was to investigate the prevalence of DOAC-treated patients with GIB whose plasma drug concentrations exceeded the cut-off values reported in the literature and to evaluate their clinical characteristics. Materials and Methods: Patients who were admitted to the Intensive Care Unit in the period 2/2020–3/2022 due to GIB were prospectively included in the study and classified into three groups according to the prescribed type of DOAC (apixaban, rivaroxaban, and dabigatran). For all participants, it was determined if the measured plasma drug levels exceeded the maximum serum concentration (Cmax) or trough serum concentration (Ctrough) obtained from the available data. A comparison of clinical parameters between the patients with and without excess drug values was performed. Results: There were 90 patients (54.4% men) included in the study, of whom 27 were treated with dabigatran, 24 with apixaban, and 39 with rivaroxaban. According to Cmax, there were 34 (37.8%), and according to Ctrough, there were 28 (31.1%) patients with excess plasma drug values. A statistically significant difference regarding excess plasma drug values was demonstrated between DOACs according to both Cmax (p = 0.048) and Ctrough (p < 0.001), with the highest rate in the group treated with dabigatran (55.6% for Cmax and 59.3% for Ctrough). Multivariate logistic regression showed that age (OR 1.177, p = 0.049) is a significant positive and glomerular filtration rate (OR 0.909, p = 0.016) is a negative predictive factor for excess plasma drug values. A total of six (6.7%) patients had fatal outcomes. Conclusions: Plasma drug concentrations exceed cut-off values reported in the literature in more than one-third of patients with GIB taking DOAC, with the highest rate in the dabigatran group. Clinicians should be more judicious when prescribing dabigatran to the elderly and patients with renal failure. In these patients, dose adjustment, plasma drug monitoring, or substitution with other, more appropriate DOACs should be considered.

show abstract

Idarucizumab for dabigatran reversal: A systematic review and meta-analysis of indications and outcomes

Cited by 8 publications

References 35 publications

Reversal or Repletion Treatment Strategies and Outcomes of Patients With Major Bleeding Events Managed in the Emergency Department: Large Real-Life Investigation in the Northwestern Healthcare District of Tuscany

Reversal or Repletion Treatment Strategies and Outcomes of Patients With Major Bleeding Events Managed in the Emergency Department: Large Real-Life Investigation in the Northwestern Healthcare District of Tuscany

Reversing dabigatran effect with idarucizumab to enable intravenous thrombolysis in patients with acute ischaemic stroke — a single centre experience

Plasma Drug Values of DOACs in Patients Presenting with Gastrointestinal Bleeding: A Prospective Observational Study

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