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PHARM 213 Cardiovascular System > 11. Fibrinolytics, antiplatelets, anticoagulants > Flashcards

11. Fibrinolytics, antiplatelets, anticoagulants Flashcards

1
Q

Agents used to prevent & treat thrombosis

A

Platelet inhibitors - Prevent the effects of arterial thrombogenesis (ACS, TIA)

Anticoagulants limit thrombus formation & prevent thromboembolism (AF, ACS)

Fibrinolytics dissolve the clot in acute arterial thrombosis & occlusion (STEMI)

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2
Q

Thrombotic response

A
  • Atherosclerotic plaques are thrombogenic
  • Thrombosis is triggered by plaque rupture &/or erosion
  • Allows blood constituents to contact pro-thrombotic factors
  • Platelet activation leads to platelet aggregation
  • Simultaneously, coagulation cascade is triggered
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3
Q

Antiplatelet therapy - Aspirin

A
  • Inactivates COX-1 activity
  • Platelet is inactivated for 8-10 days
  • Vascular endothelium can produce prostaglandins within hours
  • Clinically the effect of aspirin is antithrombotic
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4
Q

Clinical use of Aspirin in CVD

A

Primary prevention of CVD:

  • Reduces risk of ischaemic events but with a higher risk of bleeding
  • Current evidence does not support routine use of aspirin in healthy individuals

Secondary prevention of CVD:

  • Reduces risk of adverse cardiovascular events - absolute benefit outweighs risk or major-extra-cranial bleeding
  • Consider 100 mg OD in patients with prior MI or revascularisation
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5
Q

Aspirin for cardiovascular indications

A
  • Acute coronary syndrome
  • Coronary artery bypass graft (CABG) surgery
  • Transient ischaemic attack (TIA)
  • Arteriovenous shunts
  • Stroke prevention
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6
Q

P2Y12 blockers: Clopidogrel/Ticagrelor

A
  • Selectively bind to P2Y12 - ADP receptors on platelets

- This binding inhibits ADP-induced activation of the platelet GP IIb/IIIa-receptor & prevents platelet aggregation

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7
Q

Indications for P2Y12 use - Secondary prevention of CVD

A

Clopidogrel 75 mg OD is recommended:

  • Alternative to aspirin if intolerant
  • Provides slightly greater CVD risk reduction than aspirin

Ticagrelor:

  • More rapid & consistent onset of action than clopidogrel
  • Prevention of thrombotic events in patients with ACS
  • Reduces ischaemic events with no higher rate of overall bleeding
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8
Q

Dual Antiplatelet therapy (DAPT)

A

DAPT: Aspirin + P2Y12 inhibitor

  • Reduces major adverse cardiovascular events (MACE) in the year after an ACS event compared with aspirin alone
  • DAPT incorporating ticagrelor reduces MACE compared with clopidogrel
  • Used for 1 year
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9
Q

GP IIb/IIIa blockers

A

Selectively binds to platelet glycoprotein IIb/IIIa receptors preventing them from interacting with fibrinogen, vWF, reversibly blocking platelet aggregation & thrombosis formation

  • Reduce the incidence of cardiac events when used in the setting of PCI
  • Given in conjunction with aspirin + heparin + P2Y12 inhibitor
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10
Q

Anticoagulant therapy

A

Prevent thromboembolism:

  • Limit & prevent thrombus formation
  • Do not dissolve clots
  • Coagulation cascade more important than platelet activation in development of cardioembolism
  • AF & cardioembolic stroke risk - disruption of laminar flow & local inflammation
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11
Q

Anticoagulants: Warfarin

A
  • Warfarin antagonises carboxylation of clotting proteins
  • Dose as per target INR - narrow therapeutic index
  • Onset of action delayed by 2-7 days
  • Medication & food interactions
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12
Q

Non-vitamin K antagonist oral anticoagulants (NOACs)

A
  • Provide more convenient therapeutic options
  • Have demonstrated at least equivalent efficacy in comparison to warfarin, in large phase III clinical trials
  • E.g. Dabigatran, Rivaroxaban, Apixaban
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13
Q

Oral Anticoagulants (OAC) in thromboembolism prevention

A

Atrial fibrillation (AF):
- OAC is strongly recommended based on CHA2DS2-VASc score:
+ ≥ 2 (men) or ≥ 3 (women) (I, A)
+ In those with a CHA2DS2-VASc score of 1 (men) or 2 (women), consider long-term OAC (IIa, B)

  • Where possible, a NOAC is preferred over a VKA (I, A)
  • Mechanical prosthetic valves (VKA)
    + Target INR = 2.0 – 3.5
  • Venous thromboembolism (DVT/PE)
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14
Q

Choosing between VKAs & NOACs

A

NOACs offer superior stroke protection
- Except in situations with no robust data such as moderate/severe mitral stenosis, metallic valves prosthesis, very poor renal function or poor compliance

Where possible, a NOAC is preferred over a VKA

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15
Q

Dabigatran therapy considerations

A

Risk factors for bleeding include patients:

  • Being aged ≥ 75 years
  • Moderate renal impairment (creatinine clearance [CrCl] 30-50 mL/min)
  • With medication or condition(s) that increase the risk of bleeding
  • Should not be used in patients with CrCl < 30 mL/min
  • Compared to warfarin-lower risk of ischaemic stroke & intracranial bleeding
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16
Q

NOACs - summary

A
  • Offer better efficacy, safety & convenience compared with warfarin (VKA)
  • Should be considered instead of warfarin in most patients (AF, DVT/PE)
  • Insufficient evidence to recommend in mechanical heart valves
  • Advantages over warfarin – no monitoring required, no interactions with food or most medications
17
Q

Parenteral anticoagulants - Unfractioned heparin

A
  • UFH simultaneously binds to antithrombin & thrombin (factor IIa)
  • Heparin-antithrombin complex also inhibits factor Xa
  • Parenteral administration (IV, SC)
  • Dose-effect difficult to predict
  • Dose adjusted to activated Partial Thromboplastin Time (aPTT) or Activated Clotting Time (ACT)
  • Bleeding reversed by protamine
  • Complication is HIT/HITT
    + Stop & use bivalirudin (PCI for ACS) or fondaparinux (CI in PCI unless heparin bolus)
    + Regular platelet monitoring required
18
Q

Parenteral anticoagulants: Low Molecular Weight Heparins (LMWH)

A
  • 1/3 of the weight of UFH
  • Bind to antithrombin to inhibit factor Xa & some of thrombin (factor IIa)
  • The binding ratio factor Xa:IIa is 3-4:1
  • Mostly given subcutaneously in a fixed dose
  • HIT less likely (≥ 5 days; < 1%)
  • Prevention & treatment of systemic thrombosis
19
Q

Parenteral anticoagulants: Bivalirudin

A
  • Direct thrombin (factor IIa) inhibitor
  • Inhibits conversion of fibrinogen to fibrin
  • Inactivates fibrin-bound & free thrombin
  • Monitored with coagulation tests – aPTT & ACT
  • Trials – ACS with planned PCI
    + Similar outcomes to combination of UFH & GP IIb/IIIa, but less bleeding
  • Patients with HITT who are undergoing PCI should have bivalirudin
20
Q

Parenteral anticoagulants: Fondaparinux

A
  • Selective factor Xa inhibitor
  • Specific anti-Xa activity 7 times higher than LMWH
  • OASIS-5 trial – fondaparinux is superior to enoxaparin in NSTE-ACS
  • Risk of catheter thrombosis (lack of anti-IIa activity) in PCI – use of bolus UFH injection
  • Difficult to monitor (no aPTT or ACT) (anti-Xa assay)
  • Advantage – OD dosing
21
Q

Fibrinolytic therapy

A

Plasminogen activator system binds to the clot surface & breaks down the clot

Rapid therapeutic effect achieved with:

  • Tissue plasminogen activator (tPA)
  • Tenecteplase (TNK)
  • Reteplase (rPA)
22
Q

Alteplase (tPA)

A

Clot specific – binds to fibrin in the clot & converts plasminogen to plasmin

Indications:

  • STE-ACS (with aspirin, clopidogrel, UFH)
  • Treatment of acute ischaemic stroke
  • Treatment of pulmonary embolism
  • Used as an IV infusion
23
Q

Tenecteplase

A
  • Increased fibrin specificity
  • ASSENT-2 trial (in STE-ACS), single bolus dose TNK vs tPA regimen
  • Same stroke rate & mortality at 30 days
  • Less major bleeding
  • Preferred to tPA
  • Unapproved in NZ

PHARM 213 Cardiovascular System (10 decks)

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