Please refer to Secondary prevention of stroke and TIA for appropriate antiplatelet treatment in stroke

Dual anti-platelet therapy (aspirin plus clopidogrel) for longer than 12 months is unlicensed. Dual therapy should not be prescribed for longer than 12 months unless there is a written recommendation from a consultant cardiologist which clearly defines the rare and specific indication and taking account of risks verses benefits at an individual patient level.

Special consideration should always be given when aspirin and/or clopidogrel are prescribed in combination with warfarin therapy. Such combination therapy situations should carry specific advice from the consultant caring for the patient at the time of discharge.

Aspirin

• Dispersible tablets 75mg, 300mg (£0.78 = 75mg daily)
• Gastro-resistant tablets 75mg, 300mg (£0.85 = 75mg daily)
• Suppositories 150mg, 300mg

Indications

• Secondary prevention of thrombotic cerebrovascular or cardiovascular disease
• Following coronary by-pass surgery
• Analgesia

Dose

• Usual dosage, for long term use, is 75-150mg once daily
• Dose for pain: By mouth, 300–900mg every 4–6 hours when necessary; maximum 4g daily

Notes

1. Low dose aspirin prophylaxis should not routinely be initiated for primary prevention of cardiovascular disease. Current evidence suggests the benefits and harms may be more finely balanced than previously thought, even in individuals estimated to be at high risk of experiencing cardiovascular events, including those with diabetes or elevated blood pressure (It should be noted that this conflicts with NICE guidance which recommends primary prevention with low-dose aspirin (75mg) daily in people with diabetes aged over 50 years with blood pressure less than 145/90mmHg and in those aged under 50 years with 'significant other cardiovascular risk factors', but notes the recommendation was arbitrary and there was a lack of strong evidence to support their decision).
2. There is no convincing evidence that at a daily dose of 75mg using enteric-coated rather than soluble aspirin reduces the risk of gastrointestinal bleeding. They are included for the use in patients who have their medication included in a weekly blister pack system.
3. Owing to an association with Reye's syndrome, aspirin-containing preparations should not be given to children under 16 years, unless specifically indicated, e.g. for Kawasaki disease.

Clopidogrel

• Tablets 75mg (£1.11)
• Tablets 300mg

Dose and indication

• Prevention of atherothrombotic events in peripheral arterial disease or after myocardial infarction or ischaemic stroke
  • 75mg once daily
• Acute coronary syndrome (without ST-segment elevation)
  • Initially 300mg then 75mg daily (with aspirin)
• Acute myocardial infarction (with ST-segment elevation)
  • Initially 300mg then 75mg daily (with aspirin); initial dose omitted if patient over 75 years of age
• Secondary prevention following stroke or TIA
• Summary of duration of therapy
  • STEMI - 3 months (NICE specifies at least 4 weeks)
  • NSTEMI - 12 months
  • STEMI with bare metal stent - 3 months
  • STEMI with drug eluting stent - 12 months
  • NSTEMI with bare metal or drug eluting stent - 12 months
  • Elective PCI with bare metal stent - 1 month
  • Elective PCI with drug eluting stent - 12 months

Notes

1. Concomitant use of clopidogrel and omeprazole or esomeprazole is to be discouraged unless considered essential. Check whether patients who are taking clopidogrel are also buying omeprazole. Other gastrointestinal therapy such as H2 blockers (except cimetidine) or antacids may be more suitable in some patients.
2. NICE TA210: Evidence-based recommendations on clopidogrel and modified-release dipyridamole for preventing occlusive vascular events in adults (December 2010):
   1. Clopidogrel is recommended as an option to prevent occlusive vascular events:
      1. for people who have had an ischaemic stroke or who have peripheral arterial disease or multivascular disease or
      2. for people who have had a myocardial infarction only if aspirin is contraindicated or not tolerated.
   2. Treatment with clopidogrel to prevent occlusive vascular events should be started with the least costly licensed preparation.
3. MHRA Drug Safety Update (April 2010): Discourage concomitant use of other known CYP2C19-inhibiting medicines with clopidogrel because these are expected to have a similar effect to omeprazole and esomeprazole (CYP2C19 inhibitors include; fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine and chloramphenicol).

Dipyridamole

• Tablets 100mg (£34.77 x 84 tablets)
• Modified-release capsules 200mg (£13.15 x 60 capsules)
• Suspension sugar free 50mg in 5ml (£211.27 x 150ml)

Indications

• Standard and modified release: adjunct to oral anticoagulation for prophylaxis of thromboembolism associated with prosthetic heart valves
• Modified release: secondary prevention of ischaemic stroke and transient ischaemic attacks, in combination with aspirin

Dose

• Modified release: one capsule twice daily
• Standard release: 300-600mg daily in three or four doses

Notes

1. NICE TA210: Evidence-based recommendations on clopidogrel and modified-release dipyridamole for preventing occlusive vascular events in adults (December 2010):
   1. Modified-release dipyridamole in combination with aspirin is recommended as an option to prevent occlusive vascular events:
      1. for people who have had a transient ischaemic attack or
      2. for people who have had an ischaemic stroke only if clopidogrel is contraindicated or not tolerated.
   2. Modified-release dipyridamole alone is recommended as an option to prevent occlusive vascular events:
      1. for people who have had an ischaemic stroke only if aspirin and clopidogrel are contraindicated or not tolerated or
      2. for people who have had a transient ischaemic attack only if aspirin is contraindicated or not tolerated.

Prasugrel

• Tablets 5mg, 10mg (£35.40 = 28 tablets x 5mg. £5.71 = 28 tablets x 10mg)

Indications

• In combination with aspirin for the prevention of atherothrombotic events in patients with acute coronary syndrome undergoing percutaneous coronary intervention

Dose

• Initially 60mg as a single dose then, body-weight over 60kg 10mg once daily or body-weight under 60kg, or over 75 years of age, 5mg once daily
• The treatment period for prasugrel should not exceed 12 months

Notes

1. NICE TA317 Prasugrel for the treatment of acute coronary syndromes with percutaneous coronary intervention (July 2014)
2. To be initiated only by a Consultant Cardiologist in line with NICE guidance and also for patients who otherwise would be treated with clopidogrel but who are intolerant / allergic to clopidogrel. The use of prasugrel in this patient group is only within the licensed indications for prasugrel. Allergy/intolerance is defined as a skin reaction such as rash or pruritis
3. MHRA Drug Safety Update (May 2011): Prescribers should be aware of the potential risk of rare but serious hypersensitivity reactions with prasugrel and should monitor for signs in all patients, including those with a previous known history of hypersensitivity reactions to thienopyridines. When prescribing prasugrel, inform patients of the potential risk of hypersensitivity reactions, including angioedema.

Ticagrelor

• Tablets 60mg, 90mg (£54.60)

Indications and dose

• In combination with aspirin for the prevention of atherothrombotic events in patients with acute coronary syndrome (ACS):
  • initially 180mg as a single dose, then 90mg twice daily for a maximum of 12 months
• In combination with aspirin for the prevention of atherothrombotic events after myocardial infarction (MI) in those at high risk of a further event:
  • 60mg twice daily for a maximum of 3 years as continuation therapy after the initial 12 months treatment with ticagrelor 90mg twice daily (or other adenosine diphosphate (ADP) receptor inhibitor therapy in patients with ACS). Treatment can also be started up to 2 years from the MI, or within 1 year after stopping previous ADP receptor inhibitor treatment

Notes

1. High risk of a further atherothrombotic event, the presence of at least 1 of the following 5 risk factors:
   1. Age 65 years or over or
   2. Diabetes mellitus requiring medication or
   3. A 2nd prior MI or
   4. Evidence of multi-vessel coronary artery disease or
   5. Chronic non-end stage renal dysfunction (creatinine clearance <60ml/min)
2. Please refer to: NICE TA236 Ticagrelor for the treatment of acute coronary syndromes (October 2012). To be initiated only by a Consultant Cardiologist in line with NICE guidance.
3. Please refer to: NICE TA420 Ticagrelor for preventing atherothrombotic events after myocardial infarction- guidance (December 2016)

Abciximab

• Injection 10mg in 5ml

Notes

1. NICE TA47 Acute coronary syndromes - glycoprotein IIb/IIIa inhibitors (September 2002)
2. NICE TA230 Myocardial infarction (persistent ST-segment elevation) – bivalirudin (July 2011)
3. NICE CG94 Unstable angina and NSTEMI(March 2010)

Eptifibatide

• Solution for injection 2mg in 1ml
• Solution for infusion 750 micrograms in 1ml

Notes

1. NICE TA47: Acute coronary syndromes - glycoprotein IIb/IIIa inhibitors (September 2002)
2. NICE TA230: Myocardial infarction (persistent ST-segment elevation) – bivalirudin (July 2011)
3. NICE CG94: Unstable angina and NSTEMI (March 2010)