Result of chaotic atrial depolarisation from multiple areas of re-entry within the atria > irregularly irregular rhythm without discreet P waves.

• Ischaemic Heart disease - 50%
• Valvular disease
• Hypertension
• electrolyte disturbance – hypokalaemia, hypomagnesaemia
• Toxicity – thyrotoxicosis, alcohol
• other

May present with palpitations, syncope, may be hypotensive

Proposed classification:

• 4S-AF scheme has 4 domains and may provide a framework for prognostic evaluation
  1. Stroke risk
  2. Symptom severity
  3. Severity of AF burden
  4. Substrate severity

• apixaban, dabigatran, edoxaban, and rivaroxaban have shown non-inferiority to warfarin in the prevention of stroke/systemic embolism.
  • NOACs were associated with a 19% significant stroke/systemic embolism risk reduction,
  • 51% reduction in haemorrhagic stroke, and similar ischaemic stroke risk reduction compared with VKAs,
  • NOACs were associated with a significant 10% reduction in all-cause mortality
• In the ACTIVE W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) trial, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel was less effective than warfarin for prevention of stroke, systemic embolism, myocardial infarction, and vascular death (the annual risk of events was 5.6% vs. 3.9%, P =0.0003), with a similar rate of major bleeding

Based on 6 symptoms, affect on daily activity is assessed:

• palpitations
• fatigue
• dizziness
• dyspnoea
• chest pain
• anxiety during AF

• the overall time spent in AF for a given period Oxford academic review 2021
• atrial high-rate episodes (AHREs) or subclinical AF lasting ≥5–6min are associated with both an increased risk of subsequent onset of clinical AF and an increased risk of stroke/thromboembolism which may be non-linear. <5min have ~1/2 the risk

Aim of Treatment: – alleviate symptoms and prevent complications esp stroke Treatment options: anticoagulation, rate control, rhythm control (DC reversion, ablation, chemical)

Randomized clinical trials on AF have shown no influence on survival, stroke or heart failure with rhythm control using antiarrhythmic drugs and/or cardioversions for paroxysmal or persistent AF

Anticoagulation(Quick View)close
Coagulation

Parenteral Anticoagulants

Heparin

1 (unfractionated) initiates anticoagulation rapidly but has a short duration of action
2 can be used in those at high risk of bleeding because its effect can be terminated rapidly by stopping the infusion.


Heparinoids
  role in patients who develop heparin-induced thrombocytopenia.


LMWH
  as effective but preferred because have a lower risk of heparin-induced thrombocytopenia.
  standard prophylactic regimen does not require anticoagulant monitoring
  Compared with UFH, LMWHs have higher anti-Xa/anti-IIa ratios
  LMWHs also seem to differ in their effects on platelet function
  because of their marked pharmacological differences between LMWHs, there are no agreed equivalent doses

Fondaparinux synspan_hetic pentasaccharide span_hat inhibits activated factor X.
Does not inactivate span_hrombin (factor IIa), has no effect on platelets and does not X-react wispan_h serum of patients wispan_h HIT
Tinzaparin fewest indications
175 IU/kg/day for DVT
Dalteparin VTE prevention

Enoxaparin VTE prevention, DVT Rx, ACS






Oral Anticoagulants
  newer oral anticoagulant drugs have the advantage of the ability to administer at fixed doses without the need of laboratory monitoring

Rivaroxaban - direct inhibitor of activated factor X (Xa).
- fixed daily oral dose of 10 mg for VTE
Dabigatran - selective, reversible, direct span_hrombin inhibitor
- dosing schedules of dabigatran are 150 mg and 220 mg daily
- reports of an association of dabigatran wispan_h an increased risk of myocardial infarction or acute coronary syndrome

Apixaban direct factor Xa inhibitor
-2.5 mg twice daily






Antiplatelet agents
Antiplatelet drugs are classified on mechanism of action. (View cycle) close   metabolic inhibitors
  ADP rec blockers
  platelet-platelet interaction inhibitors

Aspirin • Irreversible dose dependent inhibition of span_he TXA₂ paspan_hway
• Low dose inhibits cycloxygenase-1 (COX-1) in such a way span_hat only TXA₂ production is inhibited and not PGI₂
• Platelet function returns to normal 5-7/7 after cessation
Dipyridamole • Phosphodiesterase inhibitor - prevents span_he inactivation of cAMP
• second action - inhibition of span_hromboxane synspan_hase, span_hus reducing platelet activation
• effect is relatively short-lived - repeated dosing or slow-release preparations are required in order to achieve 24-hour inhibition of platelet function, span_herefore used more if CI to clopidogrel
• Side effects relate to its vasodilatory properties
• Platelet function returns to normal 24/24 after cessation
Clopidogrel • Clopidogrel is a prodrug, one of whose metabolites is an inhibitor of ADP-induced platelet aggregation (binds to P2Y₁₂ rec)
• PPIs inhibit antiplatelet effects, debate about significance.
• Platelet function returns to normal 5-7/7 after cessation
Ticagrelor • oral antagonist at span_he P2Y₁₂ adenosine diphosphate receptor
• inhibits platelet aggregation and span_hrombus formation in aspan_herosclerotic disease






Anticoag strategies
  Without VTE prophylaxis, the overall VTE incidence in medical and general surgery hospitalized patients: 10%-40%, & major orthopaedic surgery: 40-60%
  routine VTE prophylaxis, fatal pulmonary embolism is uncommon in orthopaedic patients and the rates of symptomatic VTE within three months: 1.3-10%.
  Hypercoagulability can persist for 3/12 after some orthopaedic surgery

Condition Strategy
AF
ACS
TIA
Lower limb immobilisation * Routine use of VTE prophylaxis in ambulatory patients in a short leg cast is controversial
* NICE guidance: 'consider' if risk of VTE outweighs risk of bleed
Spinal cord injury VTE prophylaxis wispan_h LMWH once haemostasis restored, if no evidence of spinal haematoma






Pro-coagulants


Tranexamic acid A synthetic lysine analogue with several mechanisms of action:   inhibits conversion of plasminogen to plasmin by preventing plasminogen from binding to the fibrin molecule
  inhibits plasmin activity directly, although only at higher doses
  inhibits fibrin cleavage
  blocks binding of α2-antiplasmin and inhibits inflammatory reactions
  10x more potent than epsilon‐aminocaproic acid (EACA)
  renal clearance with half-life = 2-3/24
  usual dose - 1-1.5g bd, tds
Useful in:   Gastrointestinal bleeding
  Menorrhagia
  Epistaxis
  Hereditary angioneurotic oedema
  other massive bleeding

References include: https://bnf.nice.org.uk/treatment-summary/parenteral-anticoagulants.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2827912/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941651/
aspirin pharmacol
Briish J cardiol anticoag module
NCBI article tranexamic acid
NICE review Ticagrelor
JAHA oral anticoags - challenges

• Apixaban – with non-valvular AF with ≥1 risk factors
• Dabigatran etexilate
• Rivaroxaban
• Vit K antagonist – warfarin for patients with mechanical valves
• Antiplatelets agents – not aspirin monotherapy

Bleeding and stroke risks

• CHA2DS2-VASc score for stroke risk
• HAS-BLED for bleeding risk

af_guideline_575fm.pdf

Euro Heart J: 2020 ESC AF guidelines