Endovascular Treatment for Acute Ischemic Stroke in the Setting of Anticoagulation
Background and Purpose—Oral anticoagulation (OAC) plays a major role in atrial fibrillation stroke prevention but represents a contraindication to intravenous tissue-type plasminogen activator. Intra-arterial therapy remains a potential reperfusion strategy in these patients; however, supporting data are scarce.
Methods—Retrospective analysis of prospectively collected consecutive intra-arterial therapies from October 2010 to March 2015 comparing OAC (vitamin-K antagonists and novel oral anticoagulants) versus normal hemostasis versus intravenous tissue-type plasminogen activator patients. Primary safety end point is parenchymal hematoma. Secondary safety end point is 90-day mortality. Efficacy end points are successful reperfusion (modified Thrombolysis in Cerebral Infarction, 2b-3) and good outcome (90-day modified Rankin Scale score of 0–2). Logistic regression for predictors of parenchymal hematoma was performed.
Results—A total of 604 patients were qualified for the study. Baseline and outcomes variables were overall similar for vitamin-K antagonists (n=29) and novel oral anticoagulants (n=17) patients. When compared with normal hemostasis (n=265) and intravenous tissue-type plasminogen activator (n=297), OAC (n=46) patients were older and had more comorbidities. There were no statistically significant differences in the rates of parenchymal hematoma (8% versus 5%; P=0.42), 90-day modified Rankin Scale score of 0 to 2 (30% versus 40%; P=0.26), and 90-day mortality (32% versus 26%; P=0.46) among OAC and normal hemostasis patients. Similarly, there were no significant differences between OAC and intravenous tissue-type plasminogen activator patients in terms of parenchymal hematoma (8% versus 4%; P=0.16), 90-day modified Rankin Scale score of 0 to 2 (30% versus 43%; P=0.13), and 90-day mortality (32% versus 22%; P=0.18). The use of OAC was not associated with the occurrence of parenchymal hematoma on multivariate logistic regression analysis.
Conclusions—Intra-arterial therapy seems to be safe in patients taking OACs; however, our study showed a nonsignificant increase in hemorrhage and mortality with a nonsignificant decrease in good outcomes in comparison with non-OAC patients. Although these nominal differences may have been related to older age and more comorbidities in the OAC group, larger studies are needed to confirm our findings given our limited sample size.
Atrial fibrillation accounts for 25% to 40% of all large-vessel occlusion strokes.1 Although vitamin-K antagonists (VKAs) and novel oral anticoagulants (NOACs) are the treatment of choice for stroke prevention, VKA with international normalized ratio (INR) >1.7 and recent use of NOACs represent an absolute contraindication to intravenous tissue-type plasminogen activator (tPA).2 Intra-arterial therapy (IAT) is an alternative although the data on IAT in the setting of anticoagulation are scarce. We aimed to investigate the safety and efficacy of thrombectomy in patients with therapeutic OAC use.
Patient and Variables
We reviewed our prospectively collected database for consecutive cases of IAT for acute stroke between October 2010 and March 2015. Exclusion criteria included (1) platelets <100000 per μL, (2) OAC usage with INR<2.0 (VKA with INR<1.7 included if tPA used), and (3) INR>1.7 because of reasons other than VKA. The remaining patients were categorized into 4 groups: (1) normal hemostasis, (2) therapeutic NOAC use (eg, last dose <24 hours), (3) therapeutic VKA use (eg, INR>2.0), and (4) intravenous tPA use. Primary safety end point is rates of parenchymal hematoma (PH); secondary safety end point is 90-day mortality. Efficacy end points are successful reperfusion (modified Thrombolysis in Cerebral Infarction, 2b-3) and good outcomes (90-day modified Rankin Scale score of 0–2) rates. This study was approved by the local institutional review boards.
Between-group comparisons were made with Student t test, Mann–Whitney U, ANOVA, χ2 or Fisher, as appropriate. A value of P<0.05 is statistically significant. Multivariate logistic regression analyses were performed with variables at the 0.1 level of significance (IBM SPSS Statistics 21; IBM, Armonk, NY).
Of 676 patients who underwent IAT over the study period, 72 were excluded and 604 patients underwent primary analysis.
Twenty-nine patients (5%) were on VKAs and 17 (2%) on NOACs (dabigatran, n=11; rivaroxaban, n=4; and apixaban, n=2). Baseline characteristics, efficacy, and safety end points were comparable in NOACs and VKAs groups (Table 1). These patients were combined into a single group named OAC (n=46; 7%). Four patients in the VKAs had INR>3, and none of them developed PH.
When compared with the normal hemostasis group, patients on OAC were older (P=0.01) and more frequently had atrial fibrillation (P<0.01) and diabetes mellitus (P<0.01; Table 2). Otherwise, there were no statistically significant differences in demographics, efficacy, or safety end points.
When compared with the intravenous tPA group, patients on OAC had more atrial fibrillation (P<0.01), hypertension (P=0.02), and diabetes mellitus (P=0.02) and less frequently were active smokers (P<0.01; Table 2). There was a trend toward higher Alberta Stroke Program Early CT Score (ASPECTS) in the OAC group (P=0.05) and the last-known normal to puncture time was shorter for patients who received intravenous tPA (P=0.04). Otherwise, there were no significant differences in demographics, efficacy, or safety end points.
Predictors of PH
Multivariate logistic regression indicated that neither OAC nor intravenous tPA use was associated with PH. PH was independently associated with increased mortality (odds ratio, 3.4; 95% confidence interval, 1.3–8.6; P<0.01) and hypertension (odds ratio, 0.3; 95% confidence interval, 0.1–0.7; P=0.01).
Our study shows that anticoagulated patients achieved similar rates of good angiographic and clinical outcomes than normal hemostasis and intravenous tPA without a significant increased risk of PH despite having older age and more frequent comorbidities.
The data on the safety of thrombolysis or thrombectomy in patients with stroke receiving OAC are limited to small nonrandomized observational studies.3 A published cohort of 714 thrombectomies included 28 (3.9%) on VKAs. No differences were found in hemorrhagic complications (7.1% versus 6.0%; P=0.80) or mortality (17.9% versus 21.6%; P=0.58) in anticoagulated versus nonanticoagulated patients.4 A post hoc analysis of the Mechanical Thrombectomy for Acute Ischemic Stroke (MERCI)/Multi MERCI evaluated the safety/efficacy of IAT in 35 patients with abnormal hemostasis when compared with that of IAT in 270 controls, revealing similar rates of reperfusion (Thrombolysis in Myocardial Infarction [TIMI] 2–3, 60% versus 65%), 90-day mortality (40% versus 38%), and PH (8.6% versus 8.5%).5 Specific data on IAT in the setting of NOACs remain limited to 5 case reports and have not suggested an increased risk of PH.6–9 Our NOAC cohort of 17 consecutive patients is the largest to date and further supports the safety of IAT in this population.
Atrial fibrillation was more frequent in patients taking OAC and has been associated with increased hemorrhage risk. Therefore, the absence of significantly increased hemorrhage rates in OAC patients is particularly reassuring. Our study carries all the limitations inherent to a retrospective design and the relative small sample size. Groin complications were not systematically evaluated.
IAT seems to be safe in patients taking OACs; however, our study showed a nonsignificant increase in hemorrhage and mortality with a nonsignificant decrease in good outcomes in comparison with non-OAC patients. Although these nominal differences may have been related to older age and more comorbidities in the OAC group, larger studies are needed to confirm our findings given our limited sample size.
Dr Nogueira Stryker Neurovacular (Trevo-2 Trial-PI/DWI/PWI and CTP Assessment in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention [DAWN] Trial-PI), Covidien (SOLITAIRE FR With the Intention for Thrombectomy [SWIFT]/Stent-Retriever Thrombectomy After Intravenous t-PA vs t-PA Alone in Stroke [SWIFT-PRIME] Steering Committee/Solitaire FR Thrombectomy for Acute Revascularization [STAR]-Trial Core-Lab), Penumbra (3-D Trial Executive Committee).
- Received August 24, 2015.
- Revision received August 31, 2015.
- Accepted September 9, 2015.
- © 2015 American Heart Association, Inc.
- Powers WJ,
- Derdeyn CP,
- Biller J,
- Coffey CS,
- Hoh BL,
- Jauch EC,
- et al
- Adams HP Jr,
- del Zoppo G,
- Alberts MJ,
- Bhatt DL,
- Brass L,
- Furlan A,
- et al
- De Marchis GM,
- Jung S,
- Colucci G,
- Meier N,
- Fischer U,
- Weck A,
- et al
- Nogueira RG,
- Smith WS
- Mehta S,
- Dababneh H,
- Hussain M,
- Moussavi M,
- Kirmani JF.