Acute Ischemic Stroke Pharmacotherapy Checklist

(Full update March 2024)

Use this checklist to help you keep pharmacotherapy of acute ischemic stroke patients on track from admission to discharge, and prevent readmission.


Suggested Approach

Get the correct dose of IV alteplase to qualifying patients fast (within
45 to 60 minutes).1

  • Use your institutional checklist for patient selection.6
    • In general, patients for whom IV alteplase’s benefit outweighs risk are those who present within 4.5 hrs, without: risks for brain or spinal bleeding, coagulopathy, recent trauma or surgery, aortic arch dissection, extensive regions of clear hypoattenuation on CT, endocarditis, recent gastrointestinal cancer or bleeding.1
      • IV alteplase is recommended for adults with mild but disabling to severe stroke symptoms, up to three hours from symptom onset.1
      • IV alteplase is recommended for adults in the three to 4.5 hour post-symptom-onset window who are ≤80 years of age without a history of both diabetes and prior stroke, NIHSS score ≤25, not taking oral anticoagulants, and without involvement of more than one third of the MCA territory.1
        • In this timeframe, IV alteplase is safe and can be effective for patients >80 years of age and is reasonable in patients with both diabetes and prior stroke or mild disabling stroke. Benefit in NIHSS score >25 is uncertain.1
      • Consider IV alteplase for patients who awaken with stroke symptoms even if their last known “normal” was >4.5 hours ago who have a DW-MRI lesion smaller than one-third of the MCA territory and no visible signal change on FLAIR.1
      • IV alteplase administration in stroke mimics is probably recommended over waiting for additional diagnostic studies because risk of symptomatic intracranial hemorrhage is low in this situation.1
    • Give IV alteplase to eligible patients even if thrombectomy is considered (e.g., adult with occlusion of internal carotid or M1; NIHSS score ≥6; prestroke mRS score 0 to 1; and ASPECTS ≥6, in whom treatment can be started within 6 hrs of onset). Certain patients may benefit from thrombectomy up to 24 hrs after symptom onset.1
  • Check blood glucose before administering alteplase (hypoglycemia can be the cause of stroke-like symptoms).1
  • Obtain patient weight for accurate dosing.2
  • Ensure blood pressure is not severely elevated.1
    • Blood pressure should be lowered safely to <185/110 mmHg and stable before starting IV alteplase.1
    • During and for 24 hours post-alteplase, maintain blood pressure ≤180/105 mmHg.1
  • Calculate the correct IV alteplase dose.
    • Alteplase IV: 0.9 mg/kg (max 90 mg), with 10% given as a bolus over one minute, and the rest infused over 59 minutes.1
  • Recommend a smart pump to deliver the IV alteplase bolus and infusion.7

Consider alternatives to IV alteplase.

  • Consider IV tenecteplase over IV alteplase in patients without contraindications to IV fibrinolysis who are also eligible for mechanical thrombectomy.1
    • Use is off-label, and there is more overall evidence for alteplase.
    • Long duration of action and fibrin specificity allows tenecteplase to be given as a single bolus (consider 0.25 mg/kg [max 25 mg]) instead of a one-hour infusion like IV alteplase.1,4
    • Likely more cost-effective than alteplase.12
    • In the EXTEND-IA TNK trial (large, open-label study), early reperfusion was achieved in 22% of patients with tenecteplase vs 10% of those who received alteplase within 4.5 hours of symptom onset (p=0.002 for noninferiority; p = 0.03 for superiority) [Evidence level B-1].4
    • Tenecteplase and alteplase seem to provide similar neurologic and functional outcomes (per modified Rankin scale) and mortality, with a similar rate of intracranial hemorrhage [Evidence level B-2].11
  • Consider intra-arterial (IA) alteplase (off-label use)
    • Can be used even if IV alteplase has been given.16
    • Requires timely cerebral angiography and experienced interventionalist (i.e., stroke center).1
    • Mechanical thrombectomy with stent retrievers is recommended over IA thrombolysis first-line.1
    • Reasonable to use for salvage therapy to achieve mTICI 2b/3 angiographic results.1
    • Use within six hours of stroke onset in carefully selected patients with contraindications to IV alteplase might be considered, but benefit/risk unknown.1
    • In one clinical trial (MR CLEAN), exclusion criteria were arterial blood pressure >185/110 mmHg, glucose <50 or >400 mg/dL, cerebral infarction in the distribution of the affected occluded artery in the prior six weeks, history of intracerebral hemorrhage, severe head trauma in the prior four weeks, platelets <90 x 109/L, aPTT >50, or INR >1.7, prior administration of IV alteplase in a patient with contraindications, or an IV alteplase dose of >90 mg or
      >0.9 mg/kg.16
    • Dose is not established.15 Dose per interventionalist.15 Median dose was 20 mg in the MR CLEAN registry.15 In the MR CLEAN clinical trial, a maximum permitted dose of IA alteplase was 90 mg, or 30 mg if the patient had also received IV alteplase.16 In the phase IIb CHOICE trial, intra-arterial alteplase was administered after successful reperfusion using thrombectomy, at a dose of 0.225 mg/kg (max 22.5 mg) infused over 15 to 30 minutes.14

Achieve blood pressure goals.

  • Carefully reduce and maintain blood pressure to ≤185/110 mmHg before IV thrombolysis.1
    • Consider labetalol 10 to 20 mg IV over 1 to 2 min, repeated once OR nicardipine 5 mg/hr IV, titrated by 2.5 mg/hr every 5 to 15 min (max 15 mg/hr) OR clevidipine 1 to 2 mg/hr, titrated by doubling dose every 2 to 5 min
      (max 21 mg/hr).1
    • Hydralazine, enalaprilat, or other agents can be considered.1
  • During and after reperfusion therapy (for 24 hours post-thrombolysis), maintain blood pressure ≤180/105 mmHg.1
    • Check blood pressure every 15 min for the first 2 hours of thrombolysis, then every 30 min for 6 hours, then every hour for 16 hrs.Increase monitoring frequency if systolic is >180 mmHg or diastolic is >105 mmHg.1
    • If SBP >180-230 or DBP >105-120 mmHg, consider labetalol 10 mg bolus followed by 2 to 8 mg/min infusion, or nicardipine or clevidipine as above. If blood pressure is not controlled or diastolic >140 mmHg, consider sodium nitroprusside.1
  • For patients not receiving IV thrombolysis or endovascular therapy with blood pressure ≥220/120 mmHg, consider a blood pressure reduction of 15% within 24 hrs.1
  • Start/restart antihypertensive 72 hours after symptom onset if blood pressure ≥140/90 mmHg and patient is neurologically stable.3
  • If patient is hypotensive, increase blood pressure to support organ function (e.g., with crystalloids or colloids).1

Manage blood glucose.

  • Check glucose before thrombolysis.1
    • Treat glucose <60 mg/dL.1

Treat body temperature >38oC.

  • Administer an antipyretic.1

Manage thrombolysis



  • Discontinue thrombolytic and ACEI.1
  • Give methylprednisolone 125 mg IV.1
  • Give diphenhydramine 50 mg IV.1
  • Give famotidine 20 mg IV.1
  • For persistent angioedema, give epinephrine (0.1%) 0.3 mL subcutaneously or via nebulizer (0.5 mL).1
  • Consider medications used to treat hereditary angioedema: icatibant (Firazyr) 30 mg subcutaneous injection in abdomen repeated every 6 hours if needed (max 3 injections in 24 hours) or C1 esterase inhibitor (e.g., Berinert20 IU/kg IV x 1).1

Intracranial bleed within 24 hours of thrombolysis (based on alteplase recommendations)

In addition to appropriate labs, imaging, and supportive care:

    Stop thrombolytic.

Bleeding reversal options:

    Cryoprecipitate (factor VIII source) 10 units over 10 to 30 min. Give additional dose if fibrinogen <150 mg/dL.
    • Expect onset in 1 hr, peak in 12 hrs1.
    Tranexamic acid 1,000 mg IV over 10 min OR aminocaproic acid 4 to 5 g over 1 hr. Repeat until bleeding controlled.
    • Expect peak in 3 hrs.1

Start an antiplatelet.

  • Start aspirin 160 to 300 mg daily within 24 to 48 hours of stroke onset.1
    • Generally, wait 24 hours after thrombolysis is given to start aspirin, but consider comorbidities.1
  • In patients with minor stroke who do not receive thrombolysis, consider aspirin plus clopidogrel for 21 days, starting within 24 hours of stroke onset.1

Prevent deep venous thrombosis.

  • In immobile stroke patients, use intermittent pneumatic compression (plus aspirin and hydration) to reduce the risk of deep venous thrombosis.1
    • The benefit of low-dose subcutaneous heparin or low-molecular-weight heparin in this population is unclear.1
    • If you do not give prophylaxis, document why (by day 2 of admission) to meet quality measures (US).5

Identify and treat depression.

  • Screen post-stroke patients for depression, or ensure this is done at follow-up.1
  • Treat depression if identified.1

Optimize lipid-lowering therapy.

Help patient stop smoking.

Quickly identify and respond to in-hospital stroke.

  • Participate in the in-hospital stroke response team (this can be the same stroke team that responds to stroke patients that arrive in the emergency department).6
    • If a pharmacist is not part of the stroke response team, have a policy that the charge nurse will contact the pharmacy to inform them that a patient is being assessed for possible stroke.6
  • Participate in mock stroke alerts.6
  • Educate pharmacy staff on the signs and symptoms of stroke, and activation of the stroke alert.6
  • Have a policy that the stroke response team sends thrombolytic orders to the pharmacy STAT.6
  • Consider use of a runner to deliver the thrombolytic.6
  • Advocate for use of shorter-acting sedatives to allow for frequent neurological evaluation to promote rapid identification of stroke symptoms.6

Abbreviations: ASPECTS = Alberta Stroke Programme Early CT Score; ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; CT = computed tomography; DBP = diastolic blood pressure; DW-MRI = diffusion-weighted magnetic resonance imaging; FLAIR = fluid attenuated inversion recovery; IA = intra-arterial; IV = intravenous; M1 = middle cerebral artery segment 1; mRS = modified Rankin Scale; NIHSS = National Institutes of Health Stroke Score; PHQ = Patient Health Questionnaire; SBP = systolic blood pressure; SSRI = selective serotonin reuptake inhibitor; TIA = transient ischemic attack.

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.



Study Quality


Good-quality patient-oriented evidence.*

  1. High-quality randomized controlled trial (RCT)
  2. Systematic review (SR)/Meta-analysis of RCTs with consistent findings
  3. All-or-none study


Inconsistent or limited-quality patient-oriented evidence.*

  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. Case control study


Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

[Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56.]


  1. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-e418. Erratum in: Stroke. 2019 Dec;50(12):e440-e441.
  2. Barrow T, Khan MS, Halse O, Bentley P, Sharma P. Estimating Weight of Patients With Acute Stroke When Dosing for Thrombolysis. Stroke. 2016 Jan;47(1):228-31.
  3. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018 Jun;71(6):e13-e115. Erratum in: Hypertension. 2018 Jun;71(6):e140-e144.
  4. Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018 Apr 26;378(17):1573-1582.
  5. Joint Commission. Specifications manual for Joint Commission National Quality Measures (v2021A1). September 25, 2020. (Accessed March 27, 2024).
  6. Nouh A, Amin-Hanjani S, Furie KL, et al. Identifying Best Practices to Improve Evaluation and Management of In-Hospital Stroke: A Scientific Statement From the American Heart Association. Stroke. 2022 Apr;53(4):e165-e175.
  7. Aspirus. Alteplase administration for stroke patients. February 18, 2021. (Accessed March 27, 2024).
  8. US Preventive Services Task Force. Final recommendation statement. Depression and suicide risk in adults: screening. June 20, 2023. (Accessed March 27, 2024).
  9. American Psychological Association. Patient Health Questionnaire (PHQ-9 & PHQ-2). Last updated June 2020. (Accessed March 27, 2024).
  10. Mortensen JK, Andersen G. Pharmacological management of post-stroke depression: an update of the evidence and clinical guidance. Expert Opin Pharmacother. 2021 Jun;22(9):1157-1166.
  11. Katsanos AH, Safouris A, Sarraj A, et al. Intravenous Thrombolysis With Tenecteplase in Patients With Large Vessel Occlusions: Systematic Review and Meta-Analysis. Stroke. 2021 Jan;52(1):308-312.
  12. Gao L, Moodie M, Mitchell PJ, et al. Cost-Effectiveness of Tenecteplase Before Thrombectomy for Ischemic Stroke. Stroke. 2020 Dec;51(12):3681-3689.
  13. Kernan WN, Viera AJ, Billinger SA, et al. Primary Care of Adult Patients After Stroke: A Scientific Statement From the American Heart Association/American Stroke Association. Stroke. 2021 Aug;52(9):e558-e571.
  14. Renú A, Millán M, San Román L, et al. Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial. JAMA. 2022 Mar 1;327(9):826-835.
  15. Collette SL, Bokkers RPH, Mazuri A, et al. Intra-arterial thrombolytics during endovascular thrombectomy for acute ischaemic stroke in the MR CLEAN Registry. Stroke Vasc Neurol. 2023 Feb;8(1):17-25.
  16. Berkhemer OA, Fransen PS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. Erratum in: N Engl J Med. 2015 Jan 22;372(4):394.

Cite this document as follows: Clinical Resource, Acute Ischemic Stroke Pharmacotherapy Checklist. Pharmacist’s Letter/Pharmacy Technician’s Letter/Prescriber Insights. March 2024. [400365]

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