APT 20b - Antiplatelets

7/29/2019 APT 20b - Antiplatelets

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Oral antiplatelet drugs

October 2011


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This presentation will look at recommendations for the use ofantiplatelets:-

o Aspirin

o Clopidogrel

o Prasugrel

o Ticagrelor

o Dipyridamole

For the primary and secondary prevention of cardiovasculardisease.

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

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3/15

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Cardiovascular Disease (CVD)

For the primary prevention of CVD, aspirin should only be usedafter careful consideration of the individual risks and benefitsand consultation with the individual patient as:1

Aspirin is not licensed for primary preventiono Clopidogrel, prasugrel and ticagrelor also not licensed.

The MHRA have previously highlighted that aspirin is onlylicensed 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, particularlythe presence of risk factors for vascular disease (includingconditions such as diabetes) and the risk of gastrointestinalbleeding.1

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Aspirin should be offered to all patients after an MI, andshould be continued indefinitely.2

Clopidogrel monotherapy should not be used first-line:2

but can be considered for patients with aspirin hypersensitivity.2

Myocardial Infarction (MI)

NICE recommends 75mg aspirin daily long-term incombination with clopidogrel 75mg daily for 12 monthsafter the most recent acute episode.3

after this continue with aspirin alone.

Clopidogrel monotherapy can be considered for patients

with aspirin hypersensitivity.3

Non-ST-segment-elevation MI (NSTEMI)and Unstable angina

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For medically managed STEMI:

After a STEMI patients treated with a combination of

aspirin and clopidogrel within the first 24 hours - NICErecommends combination should be continued forat least4 weeks:2 After this continue with aspirin alone (unless other

indications to continue dual antiplatelet therapy).

Agreement should be made locally regarding who shouldbe responsible for supplying the clopidogrel: e.g. Will the whole course be supplied on discharge

prescription to prevent GP having to supply with thepossibility it may be inappropriately put onto repeat?

ST-elevation MI (STEMI)

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NICE?

Prasugrel is only licensed for use in combination with aspirinin patients with acute coronary syndromes (ACS) undergoingprimary or delayed percutaneous coronary intervention (PCI).Treatment (with prasugrel) of up-to 12 months isrecommended.4

NICE recommend prasugrel (in combination with aspirin) as anoption in people with ACS having PCI only when:-5

o immediate primary PCI for ST-segment-elevation MI is necessaryor

o stent thrombosis has occurred during clopidogrel treatment

o or

o the patient has diabetes

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eams Prasugrel: additional considerations

Prasugrel should not be initiated within primary care (MTRACrecommendation).

The potential benefits of prasugrel must be carefully balancedagainst the risk of bleeding.

Patients aged 75 years and those under 60kg in weight are atan increased risk of bleeding with prasugrel:4

o

The use of prasugrel in patients aged 75 years is generally notrecommended.

o A maintenance dose of 5mg is recommended in both groups if itis 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 strokeor TIA.4

In May 2011 the MHRA issued a warning that prasugrel hasbeen rarely associated with reports of serious hypersensitivityreactions, some of which occurred in patients with a

hypersensitivity to clopidogrel.6

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eams When is ticagrelor recommended by

NICE?7

Ticagrelor is recommended in combination with aspirin for upto 12-months in adults with acute coronary syndromes; people:

o with ST-segment-elevation myocardial infarction (STEMI), thatcardiologists 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 Twave changes on electrocardiogram suggestive of ischaemia

o plusone 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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NICE?7

Before ticagrelor is continued beyond the initial treatment, thediagnosis of unstable angina should first be confirmed, ideallyby a cardiologist.

Ticagrelor was reviewed by the Midlands Therapeutics Reviewand Advisory Committee (MTRAC) in May 2011.

It was considered to have a low place in therapy due to the lackof long-term safety and efficacy data (beyond 12 months) andthe availability of alternative treatments at lower acquisitioncosts.

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10/15

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eams Ticagrelor: additional

considerations

Ticagrelor should not be initiated within primary care(MTRAC recommendation)

Commissioners should ensure there is local guidance to stoptreatment at 12-months

There should be clear information on discharge to stop themedication at the appropriate time

Ticagrelor is licensed (in combination with aspirin) for use inpatients with ACS including those managed medically andthose treated by PCI or CABG.8

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diseaseNICE recommends:9

Clopidogrel is recommended:

o For people who have had an ischaemic stroke or who haveperipheral arterial disease or multivascular disease.

(not transient ischaemic attack - TIA )

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 whereclopidogrel 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 aspirinis not tolerated or contraindicted.

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No antiplatelet agentsare licensed forprimary prevention

For the primary preventionof CVD, aspirin should only

be used after carefulconsideration of the

individual risks and benefitsand consultation with the

individual patient.

For secondaryprevention the newerantiplatelets prasugreland ticagrelor shouldonly be prescribed in-

line with NICErecommendations.

Neither prasugrel norticagrelor should be

initiated within primary care(MTRAC

recommendations).

There should be robust systems put in place toensure patients only receive combination anti-platelet therapy (i.e. aspirin and clopidogrel,

prasugrel or ticagrelor) for the recommended

period of time.

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3.76

6.71

10.69

20.34

29.64

56.04

109.64

438.37

630.17

713.70

0 100 200 300 400 500 600 700 800

aspirin 75mg

(generic dispersible)

aspirin 75mg

(generic gastro-resistant)

aspirin 75mg

(generic)

aspirin 75mg

(Nu-Seals)

clopidogrel 75mg

(generic)

dipyridamole 100mg qd(generic)

dipyridamole 200mg bd

(Persantin Retard)

clopidogrel 75mg

(Plavix)

prasugrel 10mg

(Efient)

ticagrelor 90mg bd

(Brilique)

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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0.29

2.25

33.26

47.85

54.89

0 10 20 30 40 50 60

aspirin 75mg

(generic dispersible)

clopidogrel 75mg

(generic)

clopidogrel 75mg

(Plavix)

prasugrel 10mg & aspirin 75mg

(Efient & generic dispersible)

ticagrelor 90mg bd & aspirin 75mg

(Brilique & generic dispersible)

Cost for 28 Days

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

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1) MHRA and CHM. Drug Safety Update. October 2009.http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087716

2) National Institute for Health and Clinical Excellence. MI: Secondary Prevention. ClinicalGuideline 48. Issued March 2007. http://guidance.nice.org.uk/CG48

3) National Institute for Health and Clinical Excellence . Unstable angina and NSTEMI.Clinical Guideline 94. Issued March 2010. http://guidance.nice.org.uk/CG94

4) Summary of Product Characteristics. Prasugrel (Efient). Eli Lily and Company Ltd.www.medicines.org.uk

5) 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

6) MHRA and CHM. Drug Safety Update. May 2011.http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON117322

7) Ticagrelor for the treatment of acute coronary syndromes. TA236. National Institute forHealth and Clinical Excellence. 2011http://www.nice.org.uk/nicemedia/live/13588/56819/56819.pdf

8) Summary of Product Characteristics. Ticagrelor (Brilique). Astra Zeneca UK Limited.www.medicines.org.uk

9) National Institute for Health and Clinical Excellance. Clopidogrel and m/r dipyridamolefor prevention of occlusive vascular events. Technology Appraisal 210.http://guidance.nice.org.uk/TA210

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http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087716http://guidance.nice.org.uk/CG48http://guidance.nice.org.uk/CG94http://www.medicines.org.uk/http://guidance.nice.org.uk/TA182http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON117322http://www.nice.org.uk/nicemedia/live/13588/56819/56819.pdfhttp://www.medicines.org.uk/http://guidance.nice.org.uk/TA210http://guidance.nice.org.uk/TA210http://www.medicines.org.uk/http://www.nice.org.uk/nicemedia/live/13588/56819/56819.pdfhttp://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON117322http://guidance.nice.org.uk/TA182http://www.medicines.org.uk/http://guidance.nice.org.uk/CG94http://guidance.nice.org.uk/CG48http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON087716

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APT 20b - Antiplatelets