Antithrombotic therapy in acute stroke

  • antithrombotic medication is crucial in stroke prevention, as it significantly reduces the risk of both initial and recurrent strokes
    • antiplatelet therapy is the preferred treatment for lesions characterized by atherosclerosis and endothelial injury
    • anticoagulant agents are preferred for cardioembolism and hypercoagulable states

Non-cardioembolic stroke

  • if reperfusion therapy is not applicable, initiate antiplatelet therapy immediately to prevent an early recurrent stroke  (AHA/ASA 2021 I/A)
    • for TIA, the risk of recurrent stroke is estimated to be ~ 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]   
    • after a minor stroke, the risks are 11.5%, 15.0%, and 18.5% at these respective time points
  • due to a significant bleeding risk (at least 1.46%/year for major bleeding), it is recommended to add PPIs in the presence of factors such as:
    • age ≥ 70 years (the annual risk of major bleeding is 4.1% at the age > 85 !!!) [Linxin, 2017]
    • peptic ulcer diagnosis (with or without a history of bleeding)
    • concomitant anticoagulation
    • dual antiplatelet therapy (DAPT)
    • concomitant corticosteroids
    • history of dyspepsia or gastroesophageal reflux disease (GERD)
  • a fixed combination of ASA + omeprazole (YOSPRALA) is available    →  more
  • the efficacy of anticoagulants in treating acute non-cardioembolic strokes has not been demonstrated
    • no significant reduction in early stroke recurrence or progression
    • the role of acute anticoagulation after endovascular procedures, in extra- and intracranial dissections, and for patients at high risk of cardioembolism is uncertain
    • acute anticoagulation may be considered for strictly selected patients (see below)

Cardioembolic stroke

  • anticoagulation is often recommended for secondary prevention of cardioembolic strokes:
  • for newly identified cardioembolic etiology, treatment initiation depends on clinical status (NIHSS) and the extent of ischemia (→ timing of anticoagulant therapy
    • meanwhile, bridging with ASA (100-300 mg) may be considered; however, robust evidence for its efficacy is lacking
  • management of acute stroke patients already receiving 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 with an initial dose of 50-325 mg, followed by a daily maintenance dose of 100mg/d, or consider clopidogrel 75 mg daily (AHA/ASA 2021 I/A)
    • no significant difference in efficacy and safety between ASA doses of 81 mg and 325 mg was shown (Jones, 2021)
    • the use of ticagrelor instead of ASA is not recommended (SOCRATES trial) (AHA/ASA 2019 III/B-R)
    • for patients with a minor stroke/TIA, consider DAPT (see below)
  • patients with prior thrombolysis
    • start antiplatelet therapy (ASA or CLP) after 24 hours post-procedure. once follow-up brain CT confirms the absence of hemorrhagic complication
    • IV aspirin administered within 90 minutes of thrombolysis resulted in a doubled incidence of symptomatic ICH (4.3% vs. 1.6%) [Zinkstok, 2012]
    • contraindication to ASA post-IVT is not absolute; guidelines permit its use under certain conditions (such as high risk of stent thrombosis in concurrent myocardial infarction)
  • failure of antiplatelet therapy (resistance)
    • it remains unclear whether patients with an acute stroke on antiplatelet therapy benefit from switching to another antiplatelet agent or increasing the dose (AHA/ASA 2021 IIb/B-NR)
    • often, aspirin is switched to clopidogrel (or vice versa); temporary DAPT may be considered – data from multicenter registry indicate efficacy  [Kim, 2015]
    • drug resistance can be verified by aggregometry or genetic testing (see the section on antiplatelet resistance)
  • for clopidogrel, a faster onset of full effect (within ~3h) can be achieved with an initial loading dose of 300-600 mg – equivalent  to 4-8 tablets
    • the loading dose is recommended in cardiology; stroke AHA/ASA guidelines from 2021 advise against it
    • both POINT (600mg) and CHANCE (300mg) trials suggest that the loading dose is safe even in minor stroke or TIA; these doses accelerate the onset of the antiplatelet effect without increasing the risk of bleeding
    • a loading dose of 180 mg was also safely tested with ticagrelor (THALES trial)
  • other antiplatelet agents
    • efficacy of tirofiban and eptifibatide remains undetermined  (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 combined with either ticagrelor or clopidogrel is more effective than SAPT when initiated early after the onset of minor stroke/high-risk TIA and treatment duration is < 90 days (Brown, 2021) (Lun, 2021)
    • the first choice combination is ASA + CLP
    • ASA+ticagrelor can be administered to patients with NIHSS 4-5 or those with contraindications to clopidogrel (ESO guidelines 2021)
  • avoid DAPT if anticoagulant therapy is planned or in case of extensive infarction (despite low NIHSS score)
  • avoid long-term DAPT (> 90 days) for stroke prevention
ASA + clopidogrel
  • despite immediate treatment with ASA, some patients still experience early stroke recurrence; therefore, new antiplatelets or combinations have been explored in the acute phase
  • the SAMMPRIS, CLAIR, CHANCE, and POINT  trials demonstrated the safety and efficacy of short-term (<3 months) dual antiplatelet therapy with ASA+CLP in patients with TIA/minor stroke (NIHSS ≤ 3)
  • the efficacy and safety of short-term DAPT versus monotherapy were also shown in:
  • long-term DAPT does not further reduce the risk of stroke recurrence and increases the risk of major bleeding events

→ more about individual antiplatelet agents here

  • DAPT (ASA+clopidogrel) may be administered for 0-90 days according to AHA/ASA 2021 (III/A) in:
    • high-risk TIA (ABCD2 score ≥4)
    • minor stroke  (NIHSS ≤ 3)
  • dosing: CLP loading dose 300 mg followed by 75 mg/day + ASA (50-325 mg/day)
  • according to a meta-analysis of the CHANCE and POINT trials, the optimal DAPT duration appears to be 3 weeks; beyond 30 days, the risk of bleeding increases (ESO guidelines 2021)  [Pan, 2019]
  • using DAPT beyond 3 months is associated with an increased risk of hemorrhagic complications (AHA/ASA 2021 III/A)
  • PPIs should be added in elderly patients (> 75 years of age)
  • caution is advised in patients after thrombolysis (with or without extensive ischemia) due to the increased risk of hemorrhagic transformation of ischemia; DAPT has not been evaluated in these patients

Triple antiplatelet therapy

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

Anticoagulant therapy for acute stroke

  • in general, immediate anticoagulant therapy is not recommended for patients with acute ischemic stroke (AHA/ASA 2019 III/A)
    • heparin and low molecular weight heparins (LMWH) in the acute phase either do not reduce the risk of early stroke recurrence, or their subtle effect is counteracted by a higher incidence of bleeding ( FISS-tris) [Wong, 2007]
    • this is also applies to patients with AFib (IST trial) [Saxena, 2001]
    • the risk of bleeding is highest:
      • during the first 10-14 days after the stroke
      • in large infarct and severe deficit
      • in patients with poorly compensated hypertension
  • management of acute stroke patients already on anticoagulant therapy is discussed here
  • acute anticoagulation may be considered in the following scenarios (although clinical trials have not shown efficacy):
    • intracardiac or aortic thrombosis   Aortic arch thrombus (on CTA and echocardiography)
    • thrombotic stenosis or occlusion of the CCA and ICA –  safety and efficacy are unknown (AHA/ASA 2019 IIb/C-LD)  Thrombus in the CCA in a patient with polycytemia veraTrombotic ICA occlusion
      • dual antiplatelet therapy (DAPT) may be an alternative to anticoagulation in this setting
    • TIA patients with AFib (as early secondary prevention)
  • what to do:
    • studies have shown no significant difference in efficacy between LMWH and heparin
    • start with

      • HEPARIN (preferably without bolus administration)
      • LMWH with an anti-Xa target of 0.5-1 IU/mL
      • DOACs (for TIA with Afib)
    • then switch to DOACs / warfarin (VKA)

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 bleeding risk due to congenital or acquired coagulopathies
    • thrombocytopenia
    • presence of esophageal varices
    • severe renal insufficiency (CKD)
    • history of falls per se does not predict future falls and is not an absolute contraindication

You cannot copy content of this page

Send this to a friend
you may find this topic useful:

Antiplatelet and anticoagulant therapy in acute stroke