Consequences of anti-platelet therapy (CH)

Question 1

What are anti-platelet drugs?

Answer 1

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

Question 2

What is first and second line for ACS (anti-platelet therapy)?

Answer 2

• 1st line: aspirin (lifelong) + ticagrelor (12 months)
• 2nd line: if aspirin CI, clopidogrel (lifelong)

Question 3

What is first and second line for PCI (anti-platelet therapy)?

Answer 3

• 1st line: aspirin (lifelong) + prasugrel 10mg or ticagrelor 90mg (12 months)
• 2nd line: if aspirin CI, clopidogrel (lifelong)

Question 4

What is first and second line for TIA (anti-platelet therapy)?

Answer 4

• 1st line: clopidogrel 75mg (lifelong)
• 2nd line: aspirin (lifelong) + dipyridamole (lifelong)

Question 5

What is first and second line for ischaemic stroke (anti-platelet therapy)?

Answer 5

• 1st line: aspirin 300mg daily for 2 weeks –> clopidogrel 75mg (lifelong)
• 2nd line: low-dose aspirin (lifelong) + dipyridamole (lifelong)

Question 6

What is first and second line for PAD (anti-platelet therapy)?

Answer 6

• 1st line: clopidogrel 75mg (lifelong)
• 2nd line: aspirin (lifelong)

Question 7

What are some examples of anti-platelet drugs? (6)

Answer 7

• aspirin
• clopidogrel
• dipyridamole
• prasugrel
• ticagrelor
• cangrelor (to be used under expert supervision only)

Question 8

What is the usual dosage of aspirin given?

Answer 8

75mg OD

Question 9

Describe the mechanism of aspirin.

Answer 9

Irreversibly inhibits cyclo-oxygenase (COX1 and COX2), hence blocking thromboxane A2 synthesis and reducing platelet aggregation

Question 10

What is the target of aspirin?

Answer 10

Cyclo-oxygenase

Question 11

What is aspirin used for?

Answer 11

Long-term use of low-dose aspirin is recommended in patients with established CVD (secondary prevention) - not recommended for primary prevention of CVD

Question 12

What are some examples of indications for aspirin? (6)

Answer 12

• stroke
• intermittent claudication
• stable angina
• ACS e.g. acute MI
• following coronary bypass surgery
• following placement of coronary stents

Question 13

When is aspirin monotherapy indicated?

Answer 13

Following transcatheter aortic valve implantation - if not tolerated, use clopidogrel instead

Question 14

What are some side effects of aspirin? (6)

Answer 14

• bleeding
• dyspepsia (prescribe PPI)
• asthma and bronchospasm
• haemorrhage + GI haemorrhage + subconjunctival haemorrhage
• increased bleeding time
• skin reactions

Question 15

When is aspirin contraindicated? (6)

Answer 15

• children
• hypersensitivity to aspirin / salicyclates / other NSAIDs
• severe cardiac failure
• severe hepatic impairment
• severe renal impairment
• haemophilia/other haemorrhagic disorder including thrombocytopenia

Question 16

What do we do with aspirin in pregnancy?

Answer 16

Pregnancy requires lower doses and aspirin should be avoided when breastfeeding

Question 17

What is the usual dosage of clopidogrel, and what are some alternatives?

Answer 17

• usually 75mg OD
• alt: prasugrel 10mg OD
• alt: ticagrelor 90mg BD

Question 18

Describe the mechanism of clopidogrel.

Answer 18

P2Y12 receptor antagonist –> inhibits activation of platelets by blocking activation of GPIIb/IIIa pathway

Question 19

What is the target of clopidogrel?

Answer 19

ADP

Question 20

What is clopidogrel used for?

Answer 20

Prevention of atherothrombotic events in patients with a Hx of symptomatic ischaemic disease e.g. ischaemic stroke

Question 21

When is clopidogrel used in combination with low-dose aspirin?

Answer 21

For the prevention of atherothrombotic AND thromboembolic events in patients with atrial fibrillation

And in ACS, PCI, people for whom warfarin is unsuitable

Question 22

When is clopidogrel used in combination with prasugrel?

Answer 22

Prevention of atherothrombotic events in people with ACS undergoing PCI

Question 23

When is clopidogrel used in combination with ticagrelor?

Answer 23

Prevention of atherothrombotic events in people with ACS or a Hx of MI and a high risk of developing atherothrombotic event

Question 24

When is clopidogrel monotherapy indicated?

Answer 24

When aspirin is CI e.g. aspirin sensitivity, or aspirin not tolerated despite addition of PPI (patient has high risk of GI bleeding)

Question 25

What are some side effects of clopidogrel?

Answer 25

- 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)

Question 26

When is clopidogrel contraindicated?

Answer 26

- active pathological bleeding - PUD, intracranial haemorrhage - severe hepatic impairment - caution - renal impairment, other drugs with bleeding risk, surgery

Question 27

When do we discontinue clopidogrel, prasugrel and ticagrelor before CABG surgery?

Answer 27

- clopidogrel: 5-7 days before - prasugrel: at least 7 days before - ticagrelor: 3-7 days before

Question 28

What drugs do clopidogrel interact with? (5)

Answer 28

- loperamide - montelukast - pioglitazone - repaglinide - rifampicin

Question 29

What is dipyridamole licensed for?

Answer 29

Secondary prevention of ischaemic stroke and TIAs

Question 30

Describe the mechanism of dipyridamole.

Answer 30

- inhibit uptake of adenosine into RBCs, platelets and endothelial cells - increased extracellular [adenosine] - adenosine = potent inhibitor of platelet aggregation and activation

Question 31

When is dipyridamole indicated?

Answer 31

- 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**

Question 32

What is prasugrel licensed for?

Answer 32

Prevention of atherothrombotic events in patients with ACS undergoing PCI Combination usually given for up to 12 months

Question 33

What is ticagrelor (P2Y12 receptor antagonist) licensed for?

Answer 33

Prevention of atherothrombotic events in patients with ACS Combination usually given for up to 12 months

Question 34

When is cangrelor used?

Answer 34

Anti-platelet to only be used under expert supervision

Question 35

What are glycoprotein IIb/IIIa inhibitors?

Answer 35

- 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

Question 36

What are some examples of glycoprotein IIb/IIIa inhibitors? (3)

Answer 36

- 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

Question 37

What do patients selected for PCI with the placement of a coronary stent require?

Answer 37

**Dual antiplatelet therapy** with aspirin and either cangrelor, clopidogrel, prasugrel or ticagrelor Aspirin therapy should continue indefinitely

Question 38

What is recommended following PCI for stable angina with placement of a drug-eluting stent?

Answer 38

**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