2.9 Antiplatelet drugs

2.9 Antiplatelet drugs
Abciximab inj 10mg/5ml **	R	Cardiology
Aspirin dispersible tablets 75mg, 300mg	F
Clopidogrel tablets 75mg * †	R	Aspirin intolerance only/Coronary artery stenting/Stroke/PVD/ACS
Dipyridamole tablets 25mg, 100mg, 200mg †	F
Eptifibitide inj 20mg/10ml, 75mg/100ml ‡	R	Cardiology

* See NICE guidance for Acute Coronary Syndrome - Clopidogrel

‡ See NICE guidance for Acute coronary syndromes - glycoprotein IIb/IIIa inhibitors (review)

 † See Nice guidance for Vascular disease - clopidogrel and dipyridamole

Safety of EC vs. dispersible aspirin

There is no evidence that enteric coated 75mg aspirin is safer than dispersible aspirin. Patients prescribed 75mg e/c on admission will use their own supply or be given dispersible aspirin. Patients newly prescribed the 75mg e/c will automatically get dispersible. Patients should be advised to take aspirin with or after breakfast.

Use of Clopidogrel at SMUHT

Aspirin allergy

Clopidogrel has been approved as an alternative to aspirin antiplatelet therapy for patients post-MI, post-stroke or post-CVA, who are truly allergic to aspirin (angioedema, bronchospasm). For patients with gastric intolerance to aspirin, a PPI or H2-antagonist should be added, rather than switching to clopidogrel. The CAPRIE study(1) demonstrated that clopidogrel was marginally more effective than 325mg aspirin (NNT 200 over 2 years) as an antiplatelet agent.

Bleeding risks aspirin vs. clopidogrel

Although clopidogrel has a different mode of action to aspirin, it is an antiplatelet agent and prolongs bleeding times. It should therefore be used with caution in patients who may be at risk of increased bleeding from surgery, trauma or other pathological conditions. Clopidogrel is contra-indicated in patients with active peptic ulcer or other acute pathological bleeding and should not be thought of as a safer alternative to aspirin in these patients.

In the CAPRIE trial, aspirin 325mg was compared with clopidogrel 75mg in secondary prevention of ischaemic events. Severe GI haemorrhage occurred in 0.71% and 0.49% of the groups, respectively. It is important to note that the dose of aspirin was higher than would normally be used in the UK, i.e. 75mg. Had the dose of aspirin been lower, then the rate of GI haemorrhage is likely to have been lower. For this reason, it is not appropriate to use clopidogrel as an alternative in a patient with a previous GI bleed. Patients with a previous GI bleed who require antiplatelet therapy should receive aspirin 75mg plus omeprazole 20mg daily (NEJM 2005; 352: 238-44).

Peripheral arterial disease

The vascular surgeons may sometimes favour clopidogrel over aspirin. The only available evidence comes from a subgroup analysis of CAPRIE(1), where patients enrolled with peripheral arterial disease derived greater benefit from clopidogrel than in the other subgroups. It should be noted however, that the study was not powered to look at separate subgroups.

Post-stroke or TIA

Clopidogrel is only used in patients suffering a stroke whilst taking aspirin, who have additional risk factors such as IHD, PVD or diabetes. It is only used first line in patients intolerant of aspirin. The recent MATCH trial showed that aspirin plus clopidogrel in combination did not reduce the risk of having a further ischaemic event and also caused an increase in bleeding. See also NICE guidance.

Acute Coronary Syndrome (ACS)

Patients receive a loading dose of 300mg clopidogrel followed by a combination of aspirin 75mg plus clopidogrel 75mg for a period of up to 12 months, continuing with aspirin alone. The CURE study(2) demonstrated that a substantial part of clopidogrel's benefit is achieved by 3 months. The NNT is ~50 for 3 months and nearer to 500 for the period 3-12 months. The cardiologists do not have a consensus on the duration of treatment with clopidogrel, however the maximum licensed course of combination treatment is one year. In the CURE study, for every 2 extra patients who avoided a major clinical event, 1 had a major life-threatening bleed. (Patients with a high risk of bleeding had already been excluded from the trial). Consider GI protection in higher risk individuals.

Coronary artery stents

Patients receive a loading dose of 300mg clopidogrel on the night before or 600mg clopidogrel on the day of the procedure. Post procedure, patients should continue on a combination of aspirin and clopidogrel for between 1 and 12 months. The course length will depend on various factors. (Type of stent, elective versus non-elective). This should be clearly documented on TTO.

Recent data from the CREDO study(3) has indicated that for every 33 patients scheduled for PCI and given a loading dose of clopidogrel and then a sustained course over 12 months of aspirin plus clopidogrel instead of aspirin alone one less patient would suffer from death, MI or stroke. Cardiologists are likely to be advocating a 12-month course of clopidogrel post-stenting on the basis of this evidence. This indication is unlicensed.

1. CAPRIE steering committee. A randomised, blinded trial of clopidogrel versus aspirin in patients at risk of ischaemic events. Lancet 1996; 348: 1329-39

2. The clopidogrel in unstable angina to prevent recurrent events trial investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-elevation. N Engl J Med 2001; 345: 494-502

3. Steinhubl SR et al. Early and sustained dual antiplatelet therapy following percutaneous coronary intervention: a randomised controlled trial. JAMA 2002; 288: 2411-20