Scientific Rationale for Alteplase Contraindications in Acute Ischemic Stroke

Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al.
Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015;Dec 22:[Epub ahead of print].

The American Heart Association/American Stroke Association (AHA/ASA) published a Scientific Statement that evaluated the science underlying eligibility criteria for alteplase (intravenous tissue plasminogen activator) in acute ischemic stroke. These eligibility criteria were developed for the original alteplase pilot studies and have been carried forward over the years. This Scientific Statement is a critical review of the evidence supporting these eligibility criteria. The following are 17 key points to take away from this summary:

  1. In February 2015, the Food and Drug Administration (FDA) updated the prescribing information for alteplase to make sure it was consistent with the Physician Labeling Rule. While no additional trial data were used to inform these changes, many contraindications and warnings were removed or made less detailed as part of the update. The AHA/ASA believe that this scientific statement, along with the AHA/ASA guidelines, should guide acute ischemic stroke treatment.
  2. While older age is associated with worse outcome after ischemic stroke treatment, it does not modify the treatment effect of thrombolysis. Across all age groups, patients who are treated with alteplase are more likely to be functionally independent at 3 months. Therefore, in the 0- to 3-hour window, alteplase is recommended for patients both younger and older than 80 years old.
  3. Patients in the 0- to 3-hour window with severe strokes have a higher risk of hemorrhagic transformation than patients with more mild strokes, but these patients still benefit from alteplase.
  4. Alteplase is recommended for selected patients in the 3- to 4.5-hour window. In this window, treatment is recommended for patients older than 80 years; may be beneficial in patients taking warfarin with an international normalized ratio (INR) of <1.7; and is of uncertain benefit in patients with severe stroke (National Institute of Health Stroke Scale score >25).
  5. Patients with rapidly improving symptoms, who still have the potential for moderate impairment and disability despite the improvement, can be treated with alteplase. Providers should not delay treatment while monitoring for symptom improvement.
  6. Alteplase administration should not be delayed while awaiting platelet counts or coagulation studies unless there is a reason to suspect an abnormal result.
  7. In patients taking warfarin who have an ischemic stroke, treatment with alteplase may be reasonable if the INR is ≤1.7. The use of alteplase in patients taking: warfarin, with an INR of >1.7; a direct thrombin inhibitor; or a direct factor Xa inhibitor is not recommended.
  8. In patients who have had a major surgery within the preceding 2 weeks, alteplase can be considered, but the potential reduction in stroke-related disability should be weighed against the risk of hemorrhage at the surgical site. Discussions with the surgical service in this setting can be helpful.
  9. It is reasonable to treat patients who present with concurrent ischemic stroke and myocardial infarction with alteplase, at the stroke dose, followed by percutaneous coronary angiography. Treatment of stroke patients with alteplase within 3 months of a myocardial infarction is reasonable if they had a non–ST-segment elevation MI (STEMI) or if the STEMI involved the right or inferior myocardium. Treatment may be reasonable if the STEMI involved the left anterior myocardium.
  10. In patients with a disabling stroke who also have acute pericarditis, treatment with alteplase may be reasonable, though urgent consultation with a cardiologist is recommended. For patients with mild stroke, the benefits are less clear.
  11. In patients who have an ischemic stroke as a complication of cardiac or cerebral angiography, treatment with alteplase is reasonable.
  12. The use of alteplase to treat patients with ischemic stroke caused by endocarditis is not recommended because of an increased risk of intracranial hemorrhage.
  13. In patients with hypertension >185/110 mm Hg, alteplase is recommend if the blood pressure can be safely lowered and stabilized below 180/105 mm Hg (the post-treatment blood pressure goal.)
  14. Single or combination (e.g., aspirin and clopidogrel) antiplatelet therapy is not a contraindication to treatment with alteplase.
  15. Alteplase is probably recommended for acute ischemic stroke caused by known or suspected extracranial carotid or vertebral dissection. Treatment with alteplase is not recommended for patients with known or suspected aortic arch dissection.
  16. Patients with pre-existing disability have less neurologic improvement after alteplase, but they do not seem to have an increased risk of symptomatic hemorrhage; therefore, treatment of acute stroke with alteplase in this population may be reasonable. Treatment decisions should account for patient and family preferences and goals of care.
  17. In patients with psychogenic symptoms, conversion disorder, or malingering treated with alteplase, the risk of symptomatic intracranial hemorrhage is low. Therefore, rapid treatment with alteplase is probably recommended over delaying treatment to pursue additional diagnostic testing.

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Vascular Medicine, Lipid Metabolism, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging, Hypertension

Keywords: Brain Ischemia, Cerebral Infarction, Coronary Angiography, Endocarditis, Fibrinolytic Agents, Hypertension, Intracranial Hemorrhages, Myocardial Infarction, Myocardium, Stroke, Thrombolytic Therapy, Tissue Plasminogen Activator, Vascular Diseases

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