Safety of Endovascular Thrombectomy in Patients Receiving Non–Vitamin K Antagonist Oral Anticoagulants
Background and Purpose—Prospective data on the safety of endovascular thrombectomy in acute stroke patients on non–vitamin K antagonist oral anticoagulants are lacking.
Methods—Prospective multicenter observational study. Patients with ischemic stroke undergoing thrombectomy with or without preceding thrombolysis were enrolled into the Registry of Acute Ischemic Stroke Under New Oral Anticoagulants. Baseline characteristics and functional outcome at 3 months were assessed. Hemorrhagic transformation and symptomatic intracranial hemorrhage were analyzed. Reperfusion was graded using the modified Thrombolysis in Cerebral Infarction score.
Results—Of 28 patients treated with thrombectomy, 5 had received also systemic thrombolysis (18%). Intracranial hemorrhage was observed in 46%, but symptomatic intracranial hemorrhage occurred only in 1 patient. Successful reperfusion (Thrombolysis in Cerebral Infarction score, 2b–3) was achieved in 59%. At 3 months, 19% had a modified Rankin Scale score of 0 to 2, and mortality was 26%.
Conclusions—Thrombectomy in non–vitamin K antagonist oral anticoagulant patients seems safe although a comparatively high rate of asymptomatic hemorrhagic transformation was noted. Confirmation in larger prospective controlled cohorts is necessary.
Endovascular thrombectomy (ET) is an option in stroke patients with a contraindication for thrombolysis, such as anticoagulation, but the evidence for its safety in patients anticoagulated with non–vitamin K antagonist oral anticoagulants (NOACs) is sparse.1 In recent thrombectomy trials, the use of oral anticoagulation was either excluded2,3 or only a few anticoagulated patients were included.4,5
Here, we report the results on the safety and functional outcome after ET within the Registry of Acute Stroke Under New Oral Anticoagulants.
Registry of Acute Ischemic Stroke Under New Oral Anticoagulants was an investigator-initiated, multicenter, prospective registry (NCT01850797, http://www.clinicaltrials.gov). All management decisions were made by attending physicians. Thirty-eight certified German stroke units participated. The protocol was approved by the ethics committee of the Medical Faculty Heidelberg and the local ethics committees. Between February 1, 2012, and February 28, 2015, patients with acute ischemic stroke aged ≥18 years undergoing ET with or without intravenous thrombolysis (IVT) and therapy with NOAC at stroke onset were enrolled if informed consent by the patient or a legal representative was obtained.
Neuroradiological images were analyzed by 2 readers. Consecutive follow-up images until day 7 were analyzed (details are given in online-only Data Supplement). The main outcome variables were the occurrence of any intracranial hemorrhage (ICH) and symptomatic ICH (sICH; according to Safe Implementation of Thrombolysis in Stroke-Monitoring Study [SITS-MOST], European Cooperative Acute Stroke Study-II [ECASS-II], Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment [SWIFT-PRIME]; online-only Data Supplement). Clinical outcome at 3 months was determined by telephone interview.
χ2, Fisher exact, or Mann–Whitney U test was used for baseline and radiological outcome group comparisons. Associations of demographic and clinical characteristics with any ICH or unfavorable outcome at follow-up were measured using univariate logistic regression (details are in given in the online-only Data Supplement). Analyses were performed using IBM SPSS Statistics, version 23 (Armonk, NY), and SAS 9.3 (Cary, NC) with P values of <0.05 considered significant.
Twenty-eight patients were treated with thrombectomy alone (ET, n=23) or combined with IVT (IVT+ET, n=5).
Mean patient age was 74 years; 89% had an anterior circulation stroke (baseline characteristics are given in Table I in the online-only Data Supplement). Specific coagulation tests (available in 46%) indicated peak-range levels in 31% and trough-range in 69%. This was supported by unspecific coagulation tests (Table II in the online-only Data Supplement). For patients taking dabigatran, median activated partial thromboplastin time was not elevated, in contrast to the more sensitive thrombin time.
Procedural times are summarized in Table 1. The start of catheter angiographies was not delayed by IVT. No bleeding complications were reported at the puncture site or airway.
sICH occurred only in 1 patient who had fatal procedural vessel perforation (Table 1). Any ICH occurred in 46% of patients. In univariate analysis, no specific risk factor of sICH was identified (Table III in the online-only Data Supplement). Successful reperfusion (Thrombolysis in Cerebral Infarction score, 2b+3) was achieved in 59%, and 33% had partial reperfusion (Table 1).
At 3 months, 19% of ET patients but none of the IVT+ET patients were independent (Table 2), and 26% had died. In univariate analysis, previous ischemic stroke, male sex, and prestroke modified Rankin Scale score predicted unfavorable outcome (Table IV in the online-only Data Supplement).
Our main finding is that thrombectomy in NOAC patients was not associated with an increased rate of sICH compared with data reported in nonanticoagulated patients.
sICH only occurred in a single patient with procedural vessel rupture. This low rate of sICH (4%) is consistent with recently reported aggregate data (3%) from cohorts of patients undergoing thrombolysis alone or combined with thrombectomy.6 Forty-six percent of our patients experienced any hemorrhagic transformation. This proportion is comparable with a retrospective analysis in NOAC patients undergoing thrombectomy (53%)7 but higher than that in patients on vitamin K antagonists (27%)6 and the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN, 8%).4
Although mortality was similar, less patients experienced a favorable outcome (modified Rankin Scale score, 0–2) at 3 months than in studies reporting on mixed thrombectomy and thrombolysis cohorts.6,7 Less favorable outcomes might have been caused by the lower reperfusion rates,2–5,7,8 longer symptom onset to intervention times,9 higher age,10 and more premorbid disability in our cohort.10
Study limitations include the small sample size and the lack of a control group. Drug-specific coagulation tests indicated trough drug concentrations in the majority of patients (Table II in the online-only Data Supplement), and correspondingly unspecific coagulation tests (international normalized ratio and activated partial thromboplastin time) were frequently within the normal range. Information on the safety of the procedure at peak drug levels is, therefore, limited.
In summary, thrombectomy in NOAC patients seems reasonably safe although a comparatively high rate of asymptomatic hemorrhagic transformation was noted. Confirmation of these results in larger controlled prospective cohorts is necessary.
Sources of Funding
This study was investigator initiated, without commercial funding.
Personal fees, speakers, consulting honoraria, and research support were received from Pfizer (J.C. Purrucker, T. Rizos, R. Dziewas, C. Kleinschnitz, A. Binder, K. Gröschel, S. Poli, T. Neumann-Haefelin, P.A. Ringleb, and R. Veltkamp), BMS (T. Rizos, R. Dziewas, C. Kleinschnitz, A. Binder, K. Gröschel, S. Poli, G. Seidel, T. Neumann-Haefelin, P.A. Ringleb, and R. Veltkamp), Boehringer Ingelheim (J.C. Purrucker, R. Dziewas, C. Kleinschnitz, A. Binder, K. Gröschel, M.G. Hennerici, S. Poli, G. Seidel, T. Neumann-Haefelin, P.A. Ringleb, and R. Veltkamp), Bayer (T. Rizos, R. Dziewas, C. Kleinschnitz, A. Binder, K. Gröschel, M.G. Hennerici, S. Poli, G. Seidel, T. Neumann-Haefelin, P.A. Ringleb, and R. Veltkamp), Daiichi Sankyo (T. Rizos, R. Dziewas, C. Kleinschnitz, A. Binder, K. Gröschel, S. Poli, G. Seidel, P.A. Ringleb, and R. Veltkamp), and CSL Behring (R. Veltkamp), outside of the present work. P.U. Heuschmann received grants from German Federal Ministry of Education and Research, European Union, Charité, Berlin Chamber of Physicians, German Parkinson Society, University Hospital Würzburg, Robert-Koch-Institute, Charité–Universitätsmedizin Berlin (within Monitoring for Detection of Atrial Fibrillation in Ischemic Stroke [MonDAFIS], supported by unrestricted research grant to Charité from Bayer), University Göttingen (within Finding Atrial Fibrillation in Stroke Patients: Randomized Evaluation of Enhanced and Prolonged Holter Monitoring [Find-AF(RANDOMISED)], supported by an unrestricted research grant from Boehringer Ingelheim), and University Hospital Heidelberg (Registry of Acute Ischemic Stroke Under New Oral Anticoagulants-prime, supported by unrestricted research grant from Bayer, BMS, and Boehringer Ingelheim), outside of the present work. The other authors report no conflicts.
Guest Editor for this article was Stephen M. Davis, MD.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.116.012684/-/DC1.
- Received January 12, 2016.
- Revision received January 25, 2016.
- Accepted January 29, 2016.
- © 2016 American Heart Association, Inc.
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