Stroke, AF & Anticoag

• Stroke management guidelines include:

  • Guidelines for management of minor ischaemic stroke and TIA
  • Guidelines for management of major ischaemic stroke
  • Importance of managing AF as part of stroke prevention
• Atrial Fibrillation (AF) considerations:

  • Rate vs. rhythm control
  • Use of anticoagulants in AF
• Anticoagulation details:

  • Use of DOACs
  • Vitamin K antagonists (warfarin)
• Key stroke statistics in the UK:

  • A stroke occurs every 5 minutes
  • 100,000 people in the UK experience a stroke each year
  • There are 1.3 million stroke survivors in the UK
• Management of TIA & Minor Ischaemic Stroke:

  • DAPT should be given within 24 hours to those with a low bleed risk
  • Consider a PPI alongside DAPT to reduce the risk of gastrointestinal haemorrhage
  • High intensity statin therapy with Atorvastatin 20-80mg OD
  • Lifestyle modifications to improve cardiovascular health
• Why ticagrelor is now used for TIAs and minor strokes:

  • THALES TRIAL with 11,073 participants
  • Treatment group received a 30-day regimen of ticagrelor plus aspirin
  • Primary outcome measures: Stroke or death
  • Safety measures included bleeding risks
• Ischaemic Stroke Thrombolysis details:

  • Thrombolysis window: 4.5 hours from stroke symptom onset (up to 9 hours if specific criteria met)
  • Fibrinolytics dissolve the fibrin clot in an ischaemic stroke to restore blood flow
  • Significant risk of bleeding with fibrinolytics
• Ischaemic Stroke Thrombectomy:

  • Thrombectomy window: up to 24 hours
  • Neurosurgical procedure to physically remove a blood clot from the brain
  • Specific brain imaging required & clot must be accessible to neurosurgeons
• A stent is a small, expandable metal mesh tube inserted into an artery to keep it open, often used to treat coronary artery disease
• In atrial fibrillation (AF), over 1 million people in the UK have AF, with a 5 times greater risk of stroke for those with AF
• Detection and diagnosis of AF involves performing a manual pulse to assess for an irregular pulse and a 12-lead electrocardiogram (ECG) to make a diagnosis
• For people with AF and a CHA2DS2-VASc score of 2 or above, anticoagulation with a direct-acting oral anticoagulant (DOAC) is recommended, considering the risk of bleeding
• Rate control is offered as the first-line treatment strategy for AF, except in specific cases, with options like beta-blockers, calcium-channel blockers, and digoxin for initial monotherapy
• The AFFIRM Trial compared rate control vs. rhythm control in AF patients, showing a slightly lower 5-year mortality rate with rate control
• Warfarin is used in AF with specific INR targets depending on the clinical indication, with close monitoring essential due to its narrow therapeutic index
• Factors affecting INR levels include enzyme inhibitors that reduce warfarin metabolism and enzyme inducers that increase warfarin metabolism
• Factors affecting INR:

  • Increases INR: enzyme inhibitors (reduce warfarin metabolism) e.g. amiodarone, macrolides, quinolones, azole antifungals
  • Decreases INR: enzyme inducers (increase warfarin metabolism) e.g. carbamazepine, rifampicin, vitamin K, St. John’s wort
  • Interference with warfarin protein binding e.g. phenytoin
  • Reduced warfarin absorption (diet): reduction in vitamin K rich foods e.g. green leafy vegetables, increase in vitamin K rich foods e.g. green leafy vegetables, smoking cessation, smoking initiation, liver impairment (unable to metabolize warfarin effectively)
  • Remember pharmacodynamic drug interactions too e.g. NSAIDs, SSRIs, antiplatelets etc.
• Management of raised INR:

  • Time in Therapeutic Range (TTR): assess anticoagulation control with vitamin K antagonists
  • Reassess anticoagulation for a person with poor anticoagulation control
  • POC Monitoring: self-monitoring using POC meters
  • Community Pharmacist INR Monitoring Service: can achieve outcomes exceeding national and local targets
• DOACs vs. Warfarin:

  • Antidotes, blood tests & monitoring, bioavailability, efficacy, side effects, diet or lifestyle restrictions
  • DOAC AF Trials: comparison trials like ARISTOTLE, ENGAGE-AF TIMI 48, ROCKET-AF, RELY TRIAL
  • DOACs are now 1st line for AF due to their effectiveness and lower bleeding risk compared to warfarin
• DOAC AF Trials Summary:

  • Meta-analysis by Ruff et al. reviewed data from all 4 DOAC trials
  • Criteria for selecting DOACs based on clinical appropriateness and contraindications
• Treatment selection according to NHS England guidelines:

  • Clinicians should use edoxaban where clinically appropriate
  • If edoxaban is not suitable, consider rivaroxaban first, then apixaban or dabigatran
  • This is based on the manufacturers of edoxaban and rivaroxaban paying for AF screening.