A 76-year-old woman with atrial fibrillation (AF), remote inferior myocardial infarction, hypertension, hyperlipidemia, and type 2 diabetes mellitus is brought by ambulance to the Emergency Department after the acute onset of right-sided hemiparesis. She had been well until two hours prior to presentation, at which time she developed slurred speech and right-sided weakness. She is taking apixaban, aspirin, metoprolol, lisinopril, atorvastatin, and metformin. On presentation, she has a temperature of 98.3° F, heart rate of 94 bpm, blood pressure of 143/79 mm Hg, respiratory rate of 16 breaths per minute, and oxygen saturation of 99% on 2 L supplemental oxygen via nasal cannulae. Examination reveals mild dysarthria and right hemiparesis with National Institutes of Health Stroke Scale of 11. Non-contrast head computed tomography shows hypoattenuation involving less than one third of the left main coronary artery territory with no evidence of hemorrhage. The international normalized ratio (INR) is 1.2 and the partial thromboplastin time is 32.6 seconds. The creatinine is 0.78 mg/dL.
Which of the following statements regarding the use of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in the setting of acute ischemic stroke is correct?
The correct answer is: D. IVT/IAT may be considered in select patients taking non-vitamin K oral anticoagulants (NOACs) who present with acute ischemic stroke.
Intravenous thrombolysis (IVT) and/or intra-arterial treatment (IAT) are often considered for patients presenting with acute ischemic stroke. Among appropriately selected patients, there is an odds ratio of 1.9 for favorable outcome with IVT as compared to standard therapy.1 Options for arterial endovascular intervention include intra-arterial fibrinolysis, thrombus aspiration, mechanical thrombus retrieval, and angioplasty with stenting.1 There are numerous nuances to patient selection for IVT/IAT, but in general, these therapies are considered for patients with a disabling deficit and no contraindications who are evaluated within three to four and a half hours of symptom onset for IVT, or within six hours of symptom onset for IAT.1 Therefore, answer choice A is incorrect.
Acute ischemic stroke occurring in patients taking oral anticoagulants (OACs) is common. AF has a prevalence of 1-2%, with an annual ischemic stroke rate of 1-3% despite treatment with an OAC.2,3 Patients taking an OAC for another indication may also develop ischemic stroke. It is not fully clear how the presence of a vitamin K antagonist (VKA) or non-VKA oral anticoagulant (NOAC) should impact the decision to apply IVT or IAT in the setting of acute ischemic stroke.
Observational data suggest that the use of IVT or IAT in the presence of VKA exposure may be safe under certain conditions, particularly in patients with an INR ≤ 1.7.1,4,5 Mazya, et al. reported in 2013 on an observational cohort of 45,074 patients presenting with acute ischemic stroke. Patients taking warfarin who had an INR of ≤ 1.7 had no increased risk of intracranial hemorrhage or death compared to patients not taking warfarin.4 These findings have been corroborated by others5 and are reflected in guideline recommendations from the American Heart Association/American Stroke Association that an INR ≤ 1.7 in the setting of VKA use be considered safe for IVT/IAT.1Answer choice B is therefore incorrect.
While modest experience exists in the selection of patients taking VKAs for IVT/IAT,1,4,5 much less is known about the safety of these therapies among patients taking NOACs.1,6,7 Seiffge, et al. recently reported the preliminary results of a prospective observational cohort of 9,457 patients presenting to one of 25 centers in Europe with acute ischemic stroke treated with IVT and/or IAT2 (Recanalization Therapy for Acute Ischemic Stroke in Patients Taking NOACs M. Silverman on ACC.org). Rates of intracranial hemorrhage and death at three months among those taking a NOAC were compared to: 1) patients taking a VKA, and 2) patients receiving no anticoagulation. In this cohort, there were 441 patients taking a VKA, 47 taking rivaroxaban, 29 taking dabigatran, two taking apixaban, and none taking edoxaban. The median time since last NOAC intake was 13 hours (interquartile range [IQR] 18-22 hours), and the median INR for those taking a VKA was 1.3 (IQR 1.1-1.58). There was no difference in the primary outcomes among the NOAC, VKA, and no OAC groups. It is important to keep in mind that most of these patients were selected carefully for IVT/IAT based upon known time since last intake and normal general or drug-specific coagulation assays. Even so, this work by Seiffge, et al. offers an initial suggestion that advanced therapies for acute ischemic stroke can be provided safely to certain patients exposed to NOACs. Current guidelines recommend the consideration of IVT/IAT in patients taking a NOAC only in the presence of normal coagulation studies (ideally drug-specific) and time since last intake of ≥ 48 hours in patients with normal renal function.3 Therefore, answer choice C is incorrect and answer choice D is the preferred choice.
Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870-947.
Seiffge DJ, Van Hooff R-J V, Nolte C, et al. Recanalization Therapies in Acute Ischemic Stroke Patients. Impact of Prior Treatment with Novel Oral Anticoagulants on Bleeding Complications and Outcome A Pilot Study. Circulation 2015;132:1261-9.
Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014;43:3298-304.
Mazya MV, Lees KR, Markus R, et al. Safety of intravenous thrombolysis for ischemic stroke patients treated with warfarin. Ann Neurol 2013;74:266-74.
Xian Y, Liang L, Smith EE, et al. Risks of intracranial hemorrhage among patients with acute ischemic stroke receiving warfarin and treated with intravenous tissue plasminogen activator. JAMA 2012;307:2600-8.
Hankey GJ, Norrving B, Hacke W, Steiner T Management of acute stroke in patients taking novel oral anticoagulants. Int J Stroke 2014;9:627-32.
Diener HC, Foerch C, Riess H, Röther J, Schroth G, Weber R. Treatment of acute ischemic stroke with thrombolysis or thrombectomy in patients receiving anti-thrombotic treatment. Lancet Neurol 2013;12:677-88.