IV tPA in Patients Taking NOACs Before Ischemic Stroke

Study Questions:

Is there an increased risk of symptomatic intracerebral hemorrhage (sICH) when stroke patients taking nonvitamin K antagonist oral anticoagulants (NOACs) are treated with intravenous (IV) recombinant tissue plasminogen activator (tPA)?


The authors used data from the Get With the Guidelines (GWTG)-Stroke Registry, a nationwide voluntary registry that tracks patient-level data at participating hospitals. Patients treated with IV tPA were divided into three groups: those taking NOACs, those taking warfarin (with an international normalized ratio [INR], <1.7), and those not taking anticoagulation. Patients were included in the NOAC group if they took the medication within 7 days of arrival to the hospital. Patients who received endovascular stroke treatment were excluded. The primary outcomes were sICH, serious systemic hemorrhage, and other complications within 36 hours of IV tPA treatment. sICH was defined as ICH on imaging with notes indicating clinical deterioration due to the hemorrhage.


The study included 42,887 patients in the registry who were treated with IV tPA between October 1, 2012 and March 31, 2015. There were 251 patients taking NOACs (87 dabigatran, 129 rivaroxaban, and 35 apixaban); 1,500 patients taking warfarin with an INR of <1.7; and 41,136 patients not taking any anticoagulants before their stroke. When compared with patients on no anticoagulation, patients taking NOACs and warfarin were older, had more vascular risk factors, and had more severe strokes. Overall, 3.9% of patients had an sICH. While the unadjusted rate of sICH was higher in the NOAC (4.8%) and warfarin (4.9%) groups when compared with the no-anticoagulation group (3.9%), after adjustment, there was no association between sICH and NOAC use (adjusted odds ratio [aOR], 0.92; 95% confidence interval [CI], 0.51-1.65) or warfarin use (aOR, 0.85; 95% CI, 0.66-1.10). There was no difference in the risk of serious systemic hemorrhage or tPA complications between the groups. In secondary analyses, after adjustment for prognostic factors, in-hospital mortality was similar between the groups.


For patients in the GWTG-Stroke Registry, taking a NOAC within 7 days of stroke was not associated with an increased risk of sICH after IV tPA.


NOACs are popular alternatives to warfarin to reduce the risk of stroke in patients with atrial fibrillation; however, patients taking these medications still have ischemic strokes. Expert opinion in guideline statements indicates that IV tPA should not be given to patients taking NOACs unless sensitive coagulation parameters are normal or 48 hours has passed since the last dose. Evidence regarding the safety of IV tPA in patients who are taking NOACs is limited to case reports and a case series. Some reports have indicated that it is safe, while others describe hemorrhagic complications. Since the initial Food and Drug Administration approval of dabigatran in 2010, NOAC use has increased, making this research timely.

While the lack of association between NOAC use and sICH in this study is encouraging, as IV tPA is the mainstay of acute stroke treatment, limitations temper the results. GWTG-Stroke is a registry, and therefore, does not have details about the decision making surrounding IV tPA administration and timing of NOAC use. Patients who were not taking a NOAC within 48 hours are not anticoagulated and should be at the same risk of sICH as patients who are not taking NOACs. This nuance is not captured in the registry data. Additionally, only 251 patients taking NOACs were included, and information about testing for NOAC anticoagulant effect was not available. Additional studies will be needed to determine if patients taking NOACs can safely be treated with IV tPA.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Dyslipidemia, Prevention, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism

Keywords: Anticoagulants, Antithrombins, Atrial Fibrillation, Cerebral Hemorrhage, Hemorrhage, Hospital Mortality, International Normalized Ratio, Risk Factors, Secondary Prevention, Stroke, Thrombolytic Therapy, Tissue Plasminogen Activator, Vascular Diseases, Warfarin

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