Antithrombotic therapy in acute stroke

  • antithrombotic medication is of a paramount importance in secondary prevention and is critical in reducing the overall risk of stroke and stroke recurrence
    • antiplatelet therapy is preferred for lesions characterized by atherosclerosis and endothelial injury
    • anticoagulant agents are favored for cardioembolism and hypercoagulable states

Non-cardioembolic stroke

  • if reperfusion therapy is not indicated, start antiplatelet therapy immediately to prevent an early recurrent stroke  (AHA/ASA 2021 I/A)
    • for TIA, the estimated risk of recurrent stroke was 8.0% at seven days, 11.5% at one month, and 17.3% at three months   Recurrent stroke risk after TIA and minor stroke (Coull, 2004)    [Coull, 2004]   
    • the risks after a minor stroke were 11.5%, 15.0%, and 18.5% at these three time points
  • because of the non-negligible risk of bleeding (at least 1.46%/year for major bleeding), it is recommended to add PPIs (e.g., omeprazole, pantoprazole) if any of the following are present:
    • patients ≥ 70 years of age (at age > 85 years; the annual risk of major bleeding is 4.1% !!!) [Linxin, 2017]
    • patients with a peptic ulcer (with or without a history of bleeding)
    • concomitant anticoagulation
    • dual-antiplatelet therapy (DAPT)
    • concomitant corticosteroids
    • history of dyspepsia or gastroesophageal reflux disease (GERD)
    • fixed combination of ASA + omeprazole ( YOSPRALA) is available    →  more
  • the effectiveness of anticoagulants in acute stroke has not been demonstrated in non-cardioembolic stroke
    • no reduction in the risk of early stroke recurrence or progression
    • the role of acute anticoagulation after endovascular procedures, in extra- and intracranial dissections, and in patients at high risk of cardioembolism is unclear
    • acute anticoagulation may be considered in strictly selected patients (see below)

Cardioembolic stroke

  • anticoagulation is often indicated for secondary prevention of cardioembolic stroke:
    • in newly detected cardioembolic etiology, start the treatment according to clinical status (NIHSS) and the extent of ischemia (→ timing of anticoagulant therapy
      • in the meantime, consider bridging with ASA 100-300 mg;  however, there are no hard data on the effectiveness of this practice
    • management of acute stroke patients who are already on anticoagulant therapy is discussed here

Antiplatelet therapy in acute stroke

high-risk TIA =  ABCD2 ≥ 4

Single AntiPlatelet Therapy (SAPT)

  • without prior thrombolysis
    • start aspirin immediately at the initial dose of 50-325 mg, then 100mg/d or clopidogrel (75 mg daily) (AHA/ASA 2021 I/A)
    • there is no significant difference in effectivity and safety of ASA dose 81 mg vs. 325 mg (Jones, 2021)
    • it is not recommended to administer ticagrelor instead of ASA (SOCRATES trial) (AHA/ASA 2019 III/B-R)
    • it patients with minor stroke/TIA consider DAPT (see below)
  • patients treated with thrombolysis
    • start antiplatelet therapy (ASA or CLP) after 24 h once a follow-up brain CT  has ruled out any hemorrhagic complication
    • i.v. aspirin given within 90 minutes of thrombolysis led to a 2-fold higher incidence of symptomatic ICH (4.3% vs. 1.6%) [Zinkstok, 2012]
    • contraindication to ASA after IVT is not absolute; according to guidelines, it is allowed in specific conditions (high risk of stent thrombosis in concurrent MI, etc.)
  • failure of antiplatelet therapy (resistance)
    • it remains unclear whether patients with an acute stroke on antiplatelet therapy will benefit from switching to another antiplatelet agent or from increasing the dose (AHA/ASA 2021 IIb/B-NR)
    • often aspirin is switched to clopidogrel (or vice versa),  consider temporary DAPT (see below) – data from multicenter registry suggest efficacy  [Kim, 2015]
    • drug resistance can be verified by aggregometry or genetic testing (see the section on antiplatelet resistance)
  • in clopidogrel, acceleration of full effect (~3h) can be achieved by administering an initial dose of 300-600 mg (“loading dose”) – 4-8 tablets
    • the loading dose is officially recommended in cardiology and not recommended by AHA/ASA guidelines 2021
    • according to both the POINT (600mg) and CHANCE (300mg) studies, the loading dose appears to be safe even in minor stroke or TIA – it does not increase the risk of bleeding, only accelerates the onset of the antiplatelet effect
    • loading dose 180 mg was also safely administered in trials with ticagrelor (THALES)
  • other antiplatelet agents:
    • efficacy of tirofiban and eptifibatide is not determined  (AHA/ASA 2019 IIb/B-R)
    • IIb/IIIa receptor antagonists, including abciximab, are potentially harmful in the acute stroke phase ⇒ ↑ risk of ICH (AHA/ASA 2018 III/B-R)

Dual AntiPlatelet Therapy (DAPT)

  •  short-term dual antiplatelet therapy with aspirin and either ticagrelor or clopidogrel is effective after a minor stroke or TIA  (Lun, 2021)
    • ASA+CLP is the 1st choice
    • ASA+ticagrelor can be used in patients with NIHSS 4-5 or with CLP contraindication (ESO guidelines 2021)
  • avoid DAPT if anticoagulant therapy is planned or in case of extensive infarction (despite low NIHSS)
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Triple antiplatelet therapy

  • DAPT is superior to monotherapy in reducing the risk of stroke recurrence
  • TARDIS trial tested intensive treatment with three antiplatelet drugs (ASA+CLP+dipyridamol) against ASA+dipyridamol or CLP alone and found that triple antiplatelet therapy did not reduce the risk and severity of recurrent stroke and was associated with increased bleeding

Anticoagulant therapy in acute stroke

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Contraindications to acute anticoagulation
  • recent thrombolysis (contraindication in the first 24h)
  • brain CT/MRI showing extensive ischemia or hemorrhagic transformation of ischemia
  • general contraindications to anticoagulant therapy (rarely absolute)
    • high risk of bleeding due to congenital or acquired coagulation disorders
    • thrombocytopenia
    • presence of oesophageal varices
    • severe renal insufficiency (CKD)
    • the history of a fall per se does not predict future falls and is not an absolute contraindication

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Antiplatelet and anticoagulant therapy in acute stroke