CV Clopidogrel

Question 1

Clopidogrel

Clinical pharmacology

Common indications

Answer 1

Clopidogrel is generally prescribed with aspirin, although clopidogrel may be used alone where aspirin is contraindicated or not tolerated.

• For treatment of acute coronary syndrome (ACS), where rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce subsequent mortality.
• To prevent occlusion of coronary artery stents.
• For long-term secondary prevention of thrombotic arterial events in patients with cardiovascular, cerebrovascular and peripheral arterial disease.
• To reduce the risk of intracardiac thrombus and embolic stroke in atrial fibrillation where warfarin and novel oral anticoagulants are contraindicated.

Question 2

Mechanisms of action?

Thrombotic events occur when platelet-rich thrombus forms in atheromatous arteries and occludes the circulation

Answer 2

• Clopidogrel prevents platelet aggregation and reduces the risk of arterial occlusion by binding irreversibly to adenosine diphosphate (ADP) receptors (P2Y12 subtype) on the surface of platelets.
• As this process is independent of the cyclooxygenase pathway, its actions are synergistic with those of aspirin.

Question 3

Important adverse effects?

Answer 3

• The most common adverse effect of clopidogrel is bleeding, which can be serious, particularly if gastrointestinal, intracranial or following a surgical procedure.
• Gastrointestinal upset, including dyspepsia, abdominal pain and diarrhoea, is also common.
• As with other antiplatelet agents, clopidogrel can rarely affect platelet numbers as well as function, causing thrombocytopenia

Question 4

Warnings?

Answer 4

• Clopidogrel is a pro-drug that requires metabolism by hepatic cytochrome P450 enzymes to its active form to have antiplatelet effect.
• Its efficacy may be reduced by cytochrome P450 inhibitors by inhibiting its activation.
• Relevant examples: include omeprazole, ciprofloxacin, erythromycin, some antifungals and some SSRIs
• Where gastroprotection with a proton pump inhibitor (see Aspirin) is required for patients taking clopidogrel, lansoprazole or pantoprazole are preferred over omeprazole as they are considered less likely to inhibit clopidogrel activation.

Question 5

Practical prescribing

Prescription

Answer 5

• Clopidogrel is only available as an oral preparation. Low doses of clopidogrel require up to a week to reach their full antiplatelet effect.
• When rapid effect is needed you should prescribe a loading dose,normally 300 mg orally for ACS, in the once-only section of the drug chart before commencing a regular maintenance dose of 75 mg orally daily.

Question 6

Clinical tip?

Answer 6

Clopidogrel acts irreversibly:

• It therefore takes the lifespan of a platelet (around 7 to 10 days) for its antiplatelet effect to wear off. Clopidogrel should be stopped 7 days before elective surgery or other invasive procedures, unless the risk of stopping clopidogrel exceeds the risk of continuing.
• Thus in patients who have had a drug-eluting coronary artery stent inserted within the last 12 months, surgery should be delayed if possible.
• In emergency cases, patients taking clopidogrel may require platelet infusion to help stop bleeding.