Consequences of anti-platelet therapy (CH) Flashcards
What are anti-platelet drugs?
Decrease platelet aggregation and inhibit thrombus formation in the arterial circulation, because in faster-flowing vessels, thrombi are composed mainly of platelets with little fibrin
What is first and second line for ACS (anti-platelet therapy)?
- 1st line: aspirin (lifelong) + ticagrelor (12 months)
- 2nd line: if aspirin CI, clopidogrel (lifelong)
What is first and second line for PCI (anti-platelet therapy)?
- 1st line: aspirin (lifelong) + prasugrel 10mg or ticagrelor 90mg (12 months)
- 2nd line: if aspirin CI, clopidogrel (lifelong)
What is first and second line for TIA (anti-platelet therapy)?
- 1st line: clopidogrel 75mg (lifelong)
- 2nd line: aspirin (lifelong) + dipyridamole (lifelong)
What is first and second line for ischaemic stroke (anti-platelet therapy)?
- 1st line: aspirin 300mg daily for 2 weeks –> clopidogrel 75mg (lifelong)
- 2nd line: low-dose aspirin (lifelong) + dipyridamole (lifelong)
What is first and second line for PAD (anti-platelet therapy)?
- 1st line: clopidogrel 75mg (lifelong)
- 2nd line: aspirin (lifelong)
What are some examples of anti-platelet drugs? (6)
- aspirin
- clopidogrel
- dipyridamole
- prasugrel
- ticagrelor
- cangrelor (to be used under expert supervision only)
What is the usual dosage of aspirin given?
75mg OD
Describe the mechanism of aspirin.
Irreversibly inhibits cyclo-oxygenase (COX1 and COX2), hence blocking thromboxane A2 synthesis and reducing platelet aggregation
What is the target of aspirin?
Cyclo-oxygenase
What is aspirin used for?
Long-term use of low-dose aspirin is recommended in patients with established CVD (secondary prevention) - not recommended for primary prevention of CVD
What are some examples of indications for aspirin? (6)
- stroke
- intermittent claudication
- stable angina
- ACS e.g. acute MI
- following coronary bypass surgery
- following placement of coronary stents
When is aspirin monotherapy indicated?
Following transcatheter aortic valve implantation - if not tolerated, use clopidogrel instead
What are some side effects of aspirin? (6)
- bleeding
- dyspepsia (prescribe PPI)
- asthma and bronchospasm
- haemorrhage + GI haemorrhage + subconjunctival haemorrhage
- increased bleeding time
- skin reactions
When is aspirin contraindicated? (6)
- children
- hypersensitivity to aspirin / salicyclates / other NSAIDs
- severe cardiac failure
- severe hepatic impairment
- severe renal impairment
- haemophilia/other haemorrhagic disorder including thrombocytopenia
What do we do with aspirin in pregnancy?
Pregnancy requires lower doses and aspirin should be avoided when breastfeeding
What is the usual dosage of clopidogrel, and what are some alternatives?
- usually 75mg OD
- alt: prasugrel 10mg OD
- alt: ticagrelor 90mg BD
Describe the mechanism of clopidogrel.
P2Y12 receptor antagonist –> inhibits activation of platelets by blocking activation of GPIIb/IIIa pathway
What is the target of clopidogrel?
ADP
What is clopidogrel used for?
Prevention of atherothrombotic events in patients with a Hx of symptomatic ischaemic disease e.g. ischaemic stroke
When is clopidogrel used in combination with low-dose aspirin?
For the prevention of atherothrombotic AND thromboembolic events in patients with atrial fibrillation
And in ACS, PCI, people for whom warfarin is unsuitable
When is clopidogrel used in combination with prasugrel?
Prevention of atherothrombotic events in people with ACS undergoing PCI
When is clopidogrel used in combination with ticagrelor?
Prevention of atherothrombotic events in people with ACS or a Hx of MI and a high risk of developing atherothrombotic event
When is clopidogrel monotherapy indicated?
When aspirin is CI e.g. aspirin sensitivity, or aspirin not tolerated despite addition of PPI (patient has high risk of GI bleeding)
What are some side effects of clopidogrel?
- blood and lymphatics - thrombocytopenia, leukopenia, eosinophilia
- eye - conjunctival, ocular or retinal bleeding
- GI - haemorrhage, abdominal pain, diarrhoea, dyspepsia, ulcers, gastritis, N&V
- respiratory - epistaxis
- skin and subcutaneous tissue - bruising, rash, pruritus
- vascular - haematoma
- insulin autoimmune syndrome –> severe hypoglycaemia (especially if HLA-DRA4 subtype)
When is clopidogrel contraindicated?
- active pathological bleeding - PUD, intracranial haemorrhage
- severe hepatic impairment
- caution - renal impairment, other drugs with bleeding risk, surgery
When do we discontinue clopidogrel, prasugrel and ticagrelor before CABG surgery?
- clopidogrel: 5-7 days before
- prasugrel: at least 7 days before
- ticagrelor: 3-7 days before
What drugs do clopidogrel interact with? (5)
- loperamide
- montelukast
- pioglitazone
- repaglinide
- rifampicin
What is dipyridamole licensed for?
Secondary prevention of ischaemic stroke and TIAs
Describe the mechanism of dipyridamole.
- inhibit uptake of adenosine into RBCs, platelets and endothelial cells
- increased extracellular [adenosine]
- adenosine = potent inhibitor of platelet aggregation and activation
When is dipyridamole indicated?
- modified-release preparations licensed for secondary prevention of ischaemic stroke and TIA
- adjunct to oral anticoagulation for prophylaxis of thromboembolism associated with prosthetic heart valves
What is prasugrel licensed for?
Prevention of atherothrombotic events in patients with ACS undergoing PCI
Combination usually given for up to 12 months
What is ticagrelor (P2Y12 receptor antagonist) licensed for?
Prevention of atherothrombotic events in patients with ACS
Combination usually given for up to 12 months
When is cangrelor used?
Anti-platelet to only be used under expert supervision
What are glycoprotein IIb/IIIa inhibitors?
- examples: abciximab, eptifibatide, tirofiban
- mechanism: blocks binding of fibrinogen to GPIIb/IIIa receptors on platelet –> prevents platelet aggregation
- target: fibrinogen
- indications: high-risk patients undergoing PCI; people with ACS to prevent early MI
What are some examples of glycoprotein IIb/IIIa inhibitors? (3)
- abciximab - prevention of ischaemic complications in patients undergoing percutaneous transluminal coronary intervention
- eptifibatide (and tirofiban) - prevent early MI in patients with unstable angina or NSTEMI
- tirofiban - reduction of major CV events in patients with STEMI intended for PCI
What do patients selected for PCI with the placement of a coronary stent require?
Dual antiplatelet therapy with aspirin and either cangrelor, clopidogrel, prasugrel or ticagrelor
Aspirin therapy should continue indefinitely
What is recommended following PCI for stable angina with placement of a drug-eluting stent?
Clopidogrel + aspirin for at least 6 months (and for at least 1 month in bare-metal stent)
Clopidogrel should not be discontinued prematurely due to risk of stent thrombosis
