ISCHEMIC STROKE / THERAPY

Acute stroke in an anticoagulated patient

Created 18/04/2022, last revision 06/11/2023

anticoagulants have become the mainstay of stroke prevention in patients with atrial fibrillation (AFib) or other potential sources of cardioembolism
however, despite anticoagulant therapy, ischemic stroke can occur, and we then face two basic scenarios:
- the patient is otherwise suitable for recanalization therapy
  - can the anticoagulant´s drug effect be neutralized to allow intravenous thrombolysis (IVT)?
  - prefer direct mechanical thrombectomy (dMT) over bridging therapy?
- the patient is not not suitable for recanalization therapy
  - continue with anticoagulation therapy?
  - halt the treatment for 7-14 days and then restart?
  - when oral anticoagulation is discontinued, should aspirin (ASA) or low molecular weight heparin (LMWH) be administered temporarily? If so, at what dose?
before resuming the anticoagulant therapy, analyze the reasons for its earlier failure
- poorly adjusted warfarin with low INR
- underdosing, other drug interactions, or discontinuation of DOACs?
- other stroke mechanisms? (dissection, vasculitis, etc.)

The patient is a candidate for recanalization therapy

→ recanalization therapy in anticoagulated patients

The patient is NOT a candidate for recanalization therapy

initiation of anticoagulation therapy in the early stages of stroke is generally not recommended
continuing effective anticoagulation therapy reduces the risk of recurrence but also increases the risk of hemorrhagic transformation of ischemia (HTI)
the risk of recurrence of cardioembolic stroke in the first 14 days is relatively low according to studies (about 5-8%); the potential benefit of early anticoagulation is negated by an increased incidence of bleeding
- in the IST trial (comparing UFH vs. placebo), the recurrence risk in the heparin arm was approx. 2.3 vs. 4.9%/14 days, but the incidence of ICH was higher (2.8 vs. 0.4%) ⇒ no net benefit
- the HAEST trial compared LMWH with aspirin – the difference in stroke recurrence rate was non-significant (approx. 8% in 14 days in both groups)
rapid neutralization of the anticoagulant effect may reduce the risk of HTI compared with simple withdrawal; however, research on this is limited
ASA bridging
- according to the IST and CAST trials, the absolute reduction in stroke recurrence is approx. 1% (similar to patients without AFib). ASA does not appear to significantly reduce the risk of cardioembolism nor increase the risk of bleeding
- a meta-analysis of 3 trials (IST, CAST, and HAEST) showed minimal benefit with ASA and no benefit with heparin
LMWH bridging
- therapeutic doses should not be administered
- used only as mini-heparinization for VTE prophylaxis; intermittent pneumatic compression (IPC) is preferred for moderate-to-severe stroke → VTE prevention
the decision to discontinue or resume anticoagulation is highly individualized
when restarting the therapy, either the current DOAC or another drug can be chosen – the RENO-EXTENT trial showed similar recurrence rates for both strategies

	effective anticoagulation	ineffective anticoagulation
TIA	warfarin – increase target INR or switch to DOAC (if possible) DOAC – verify correct dosage and laboratory efficacy or switch to another agent	start DOAC (if possible) otherwise, titrate warfarin when bridging LMWH
minor stroke	discontinue anticoagulation + consider ASA bridging 100-300 mg OR continue with anticoagulation ( based on NIHSS and extent of ischemia – ideally according to DWI finding)	consider ASA bridging 100-300 mg delayed anticoagulation – timing of anticoagulant therapy
moderate-severe stroke	discontinue anticoagulation consider ASA bridging 100-300 mg delayed anticoagulation – timing of anticoagulant therapy	consider ASA bridging 100-300 mg delayed anticoagulation – timing of anticoagulant therapy
	Seek another etiology. Is there an indication for concurrent antiplatelet therapy?