Acute Ischemic Stroke Pharmacotherapy Checklist

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 hours, 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, ≤3 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
    • Emerging evidence suggests that alteplase given 4.5 to 24 hours post-stroke can increase the chance of functional independence per mRS (NNT ~8) (but with increased risk of symptomatic ICH [NNH ~30]) in patients with salvageable brain tissue on imaging but refuse or cannot undergo mechanical thrombectomy [Evidence level B-1].¹⁸
    • IV alteplase administration in stroke mimics is probably recommended over waiting for additional diagnostic studies because risk of symptomatic ICH 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 hours of onset). Certain patients may benefit from thrombectomy up to 24 hours 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
  • 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]) over five seconds instead of a one-hour infusion like IV alteplase.^1,4,19
  • 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 mRS) and mortality, with a similar rate of ICH [Evidence level B-2].¹¹
  • If patients refuse or cannot undergo mechanical thrombectomy, emerging evidence suggests that tenecteplase given 4.5 to 24 hours post-stroke increases the odds of functional independence per mRS without increasing ICH risk [Evidence level B-2].¹⁷  Selection criteria needs further delineation.
• 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 hours.¹ 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 hours.¹
• Start/restart antihypertensive 72 hours after symptom onset if blood pressure is above goal and patient is neurologically stable.³
  • See our infographics, Treatment of Hypertension and Hypertension Goals in Adults for antihypertensive options and blood pressure goals.
• 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 >38^oC.

• Administer an antipyretic.¹

Manage thrombolysis

complications.

Angioedema

• 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 1 mg/mL (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.¹ 
• Expect onset in 1 hr, peak in 12 hours¹.

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 hours.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
  • See our chart, Antiplatelets for Recurrent Ischemic Stroke, for risk/benefit information and dosing.

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
  • For screening, consider use a brief tool such as the PHQ-9 or PHQ-2 (the first two questions of the PHQ-9) (https://www.apa.org/depression-guideline/patient-health-questionnaire.pdf).^8,9,13
  • If depression is diagnosed, treatment is the same as for the general population.¹³ Consider an SSRI due to evidence in stroke patients and tolerability in older adults.¹⁰

Optimize lipid-lowering therapy.

• For help, see our FAQs, Cholesterol Guidelines (United States) or Canadian Dyslipidemia Recommendations.

Help patient stop smoking.

• See our chart, Smoking Cessation Drug Therapy, for options.

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