Alteplase for ischemic strokes in patients on oral antithrombotics
An important question, when to use tissue plasminogen activator (tPA) like alteplase for ischemic strokes in patients on oral antithrombotics (warfarin, etc)?! With stroke, "time is brain"... Giving tissue plasminogen activator (tPA) within 3 hours of stroke symptoms can increase the chance of a good recovery and reduce disability. Some patients also benefit when it's given up to 4.5 hours from the start of symptoms.
Based on this new data, the American Heart Association (AHA), the American Stroke Association (ASA), and the Canadian Stroke Strategy now recommend that tPA can be given up to 4.5 hours after onset of stroke symptoms in some patients. The guidelines do not recommend administration of tPA after the 3 hour mark to patients who were not studied in ECASS 3 (e.g., age > 80 years, current use of an oral anticoagulant, an NIH Stroke Scale score > 25, or history of stroke plus diabetes). The reason for exclusion of these patients is that efficacy of treating with tPA any later than 3 hours after onset of stroke symptoms has not been established.
- Some of the contraindications for the use of tPA, regardless of timing, include:
- Head trauma or stroke within the previous three months.
- Uncontrolled hypertension (SBP of 185 mmHg or more, or DBP of 110 mmHg or more)
- Use of oral anticoagulants with INR of more than 1.7. It gets tricky when patients are on antithrombotics, because of the higher risk of bleeding and intracranial hemorrhage.
The plot thickens even more for patients on one of the NEW anticoagulants, because there isn't good evidence about using tPA with these drugs. Gather important patient information quickly to help specialists individualize therapy with tPA and consider these rules of thumb.
- FOR warfarin, suggest tPA within 3 hours of symptom onset if the INR is 1.7 or less.
- Be aware some specialists will use tPA with an INR up to 2, because the benefit may outweigh the bleeding risk.
- FOR dabigatran, rivaroxaban, or apixaban, consider tPA within 3 hours of symptom onset if the last dose was more than 2 days ago.
- Explain these drugs have half-lives of up to 17 hours with normal renal function and it takes about 4 half-lives to clear them.
Suggest checking anticoagulation tests especially if it's not clear whether to give tPA. Recommend these tests for patients with renal insufficiency if the time of the last dose isn't known or was less than 2 days ago or for those taking a drug that might increase anticoagulant levels, such as ketoconazole. For dabigatran, suggest checking aPTT or thrombin time. Consider tPA if these tests come back normal. Ecarin clotting time is better, but it's not available at most hospitals. For rivaroxaban or apixaban, suggest checking prothrombin time. Consider tPA if it's normal. Check factor Xa activity, if possible, but it may take too long to get results.
Discourage using tPA in patients on anticoagulants if it's been more than 3 hours since symptom onset, the benefit may NOT exceed the risk of bleeding at this point. Antiplatelet drugs (aspirin, clopidogrel, prasugrel, ticagrelor). Suggest tPA for patients on just ONE antiplatelet. Some specialists will use tPA for patients on DUAL antiplatelets (clopidogrel plus aspirin, etc), but the chance for a good outcome might be lower.
References
- 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(3):870-947.
- Is Thrombolysis Safe in Patients Taking Antiplatelet Agents?. NEJM Journal. [online] Available at: https://www.jwatch.org/jn200807290000001/2008/07/29/thrombolysis-safe-patients-taking-antiplatelet.
- Miyares MA, Davis K. Newer oral anticoagulants: a review of laboratory monitoring options and reversal agents in the hemorrhagic patient. Am J Health Syst Pharm. 2012;69(17):1473-1484.
