Actions for Practice Teams

Oral antiplatelet drugs

October 2011

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What will this APT cover?

This presentation will look at recommendations for the use of antiplatelets:o o o o o Aspirin Clopidogrel Prasugrel Ticagrelor Dipyridamole

For the primary and secondary prevention of cardiovascular disease.

It will not cover the use of antiplatelets in atrial fibrillation.

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Primary Prevention of Cardiovascular Disease (CVD)

For the primary prevention of CVD, aspirin should only be used after careful consideration of the individual risks and benefits and consultation with the individual patient as:1 Aspirin is not licensed for primary prevention
o Clopidogrel, prasugrel and ticagrelor also not licensed.

The MHRA have previously highlighted that aspirin is only licensed for secondary prevention of cardiovascular disease:1
o If aspirin is used in primary prevention, the balance of benefits and risks should be considered for each individual, particularly the presence of risk factors for vascular disease (including conditions such as diabetes) and the risk of gastrointestinal bleeding.1

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Secondary Prevention of CVD

Myocardial Infarction (MI) Aspirin should be offered to all patients after an MI, and should be continued indefinitely.2 Clopidogrel monotherapy should not be used first-line:2
but can be considered for patients with aspirin hypersensitivity.2

Non-ST-segment-elevation MI (NSTEMI) and Unstable angina NICE recommends 75mg aspirin daily long-term in combination with clopidogrel 75mg daily for 12 months after the most recent acute episode.3
after this continue with aspirin alone.

Clopidogrel monotherapy can be considered for patients with aspirin hypersensitivity.3

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Secondary Prevention
ST-elevation MI (STEMI)

For medically managed STEMI:

After a STEMI patients treated with a combination of aspirin and clopidogrel within the first 24 hours - NICE recommends combination should be continued for at least 4 weeks:2 After this continue with aspirin alone (unless other indications to continue dual antiplatelet therapy). Agreement should be made locally regarding who should be responsible for supplying the clopidogrel: e.g. Will the whole course be supplied on discharge prescription to prevent GP having to supply with the possibility it may be inappropriately put onto repeat?

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When is prasugrel recommended by NICE?

Prasugrel is only licensed for use in combination with aspirin in patients with acute coronary syndromes (ACS) undergoing primary or delayed percutaneous coronary intervention (PCI). Treatment (with prasugrel) of up-to 12 months is recommended.4 NICE recommend prasugrel (in combination with aspirin) as an option in people with ACS having PCI only when:-5
o immediate primary PCI for ST-segment-elevation MI is necessary or o stent thrombosis has occurred during clopidogrel treatment o or o the patient has diabetes

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Prasugrel: additional considerations

Prasugrel should not be initiated within primary care (MTRAC recommendation). The potential benefits of prasugrel must be carefully balanced against the risk of bleeding. Patients aged 75 years and those under 60kg in weight are at an increased risk of bleeding with prasugrel:4
o The use of prasugrel in patients aged 75 years is generally not recommended. o A maintenance dose of 5mg is recommended in both groups if it is used after a careful assessment of risks and benefits

It should be noted that the SPC states that the efficacy and safety of the 5mg dose has not been prospectively assessed.

Prasugrel is contra-indicated in people with a history of stroke or TIA.4 In May 2011 the MHRA issued a warning that prasugrel has been rarely associated with reports of serious hypersensitivity reactions, some of which occurred in patients with a hypersensitivity to clopidogrel.6

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When is ticagrelor recommended by NICE?7

Ticagrelor is recommended in combination with aspirin for up to 12-months in adults with acute coronary syndromes; people:
o with ST-segment-elevation myocardial infarction (STEMI), that cardiologists intend to treat with PCI or o with non-ST-segment-elevation myocardial infarction (NSTEMI) or o admitted to hospital with unstable angina, defined as ST or T wave changes on electrocardiogram suggestive of ischaemia o plus one of the following characteristics:
age 60 years or older previous myocardial infarction or previous coronary artery bypass grafting (CABG); coronary artery disease with stenosis of 50% in at least two vessels; previous ischaemic stroke previous transient ischaemic attack, carotid stenosis of 50%, or cerebral revascularisation diabetes mellitus peripheral arterial disease or chronic renal dysfunction, defined as a creatinine clearance of less than 60 ml/1.73 m2 .

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When is ticagrelor recommended by NICE?7

Before ticagrelor is continued beyond the initial treatment, the diagnosis of unstable angina should first be confirmed, ideally by a cardiologist. Ticagrelor was reviewed by the Midlands Therapeutics Review and Advisory Committee (MTRAC) in May 2011. It was considered to have a low place in therapy due to the lack of long-term safety and efficacy data (beyond 12 months) and the availability of alternative treatments at lower acquisition costs.

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Ticagrelor: additional considerations

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Ticagrelor should not be initiated within primary care

(MTRAC recommendation)

Commissioners should ensure there is local guidance to stop treatment at 12-months There should be clear information on discharge to stop the medication at the appropriate time Ticagrelor is licensed (in combination with aspirin) for use in patients with ACS including those managed medically and those treated by PCI or CABG.8

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Secondary prevention: Vascular disease

NICE recommends:9 Clopidogrel is recommended:
o For people who have had an ischaemic stroke or who have peripheral arterial disease or multivascular disease.
(not transient ischaemic attack - TIA )

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M/R dipyridamole and aspirin in combination is recommended (now not limited to 2 years duration):
o For people who have had a TIA (clopidogrel is not licensed for TIA). o For people who have had an ischaemic stroke and where clopidogrel is not tolerated or contraindicated.

M/R dipyridamole alone is recommended:

o For people who have had an ischaemic stroke and where clopidogrel and aspirin are not tolerated or contraindicated. o For people who have had a transient ischaemic attack and aspirin is not tolerated or contraindicted.

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Key Messages and Actions

No antiplatelet agents are licensed for primary prevention
For the primary prevention of CVD, aspirin should only be used after careful consideration of the individual risks and benefits and consultation with the individual patient.

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For secondary prevention the newer antiplatelets prasugrel and ticagrelor should only be prescribed inline with NICE recommendations.

Neither prasugrel nor ticagrelor should be initiated within primary care (MTRAC recommendations).

There should be robust systems put in place to ensure patients only receive combination antiplatelet therapy (i.e. aspirin and clopidogrel, prasugrel or ticagrelor) for the recommended period of time.

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Cost Comparisons
ticagrelor 90mg bd (Brilique) prasugrel 10mg (Efient) clopidogrel 75mg (Plavix) dipyridamole 200mg bd (Persantin Retard) 109.64 56.04 29.64 20.34 10.69 6.71 3.76 0 100 200 300 Annual Cost
Please note that whilst we have tried to compare similar doses the doses quoted above do not imply therapeutic equivalence.

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713.70 630.17 438.37

dipyridamole 100mg qd (generic) clopidogrel 75mg (generic)

aspirin 75mg (Nu-Seals) aspirin 75mg (generic) aspirin 75mg (generic gastro-resistant) aspirin 75mg (generic dispersible)

400

500

600

700

800

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Cost Comparisons
ticagrelor 90mg bd & aspirin 75mg (Brilique & generic dispersible)

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54.89

prasugrel 10mg & aspirin 75mg (Efient & generic dispersible)

47.85

clopidogrel 75mg (Plavix)

33.26

clopidogrel 75mg (generic)

2.25

aspirin 75mg (generic dispersible)

0.29

10

20 Cost for 28 Days

30

40

50

60

Please note that whilst we have tried to compare similar doses the doses quoted above do not imply therapeutic equivalence.

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References
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8) 9)

MHRA and CHM. Drug Safety Update. October 2009. http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087716 National Institute for Health and Clinical Excellence. MI: Secondary Prevention. Clinical Guideline 48. Issued March 2007. http://guidance.nice.org.uk/CG48 National Institute for Health and Clinical Excellence . Unstable angina and NSTEMI. Clinical Guideline 94. Issued March 2010. http://guidance.nice.org.uk/CG94 Summary of Product Characteristics. Prasugrel (Efient). Eli Lily and Company Ltd. www.medicines.org.uk <accessed 26.9.11> National Institute for Health and Clinical Excellence. Prasugrel for treatment of acute coronary syndromes with PCI. Technology Appraisal 182. http://guidance.nice.org.uk/TA182 MHRA and CHM. Drug Safety Update. May 2011. http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON117322 Ticagrelor for the treatment of acute coronary syndromes. TA236. National Institute for Health and Clinical Excellence. 2011 http://www.nice.org.uk/nicemedia/live/13588/56819/56819.pdf <accessed 10/2011> Summary of Product Characteristics. Ticagrelor (Brilique). Astra Zeneca UK Limited. www.medicines.org.uk <accessed 26.9.11> National Institute for Health and Clinical Excellance. Clopidogrel and m/r dipyridamole for prevention of occlusive vascular events. Technology Appraisal 210. http://guidance.nice.org.uk/TA210