Antiplatelet dosage for PCIOverview: Percutaneous coronary intervention (PCI) is an important advance in the treatment of patients with acute coronary syndromes, with or without ST segment elevation. Despite the capacity of PCI to reduce major cardiovascular events, the risk of thrombotic complications remains an important concern. Hence, attention is being focused on the development of fast-acting anti-platelet regimens that achieve high levels of platelet inhibition.
Current advice: Aspirin, in combination with clopidogrel – a thienopyridine adenosine diphosphate receptor antagonist – prevents major thrombotic events in patients undergoing PCI and has been the standard of care for more than a decade.NICE guidance on the early management of unstable angina and non ST segment elevation myocardial infarction recommends offering a single loading dose of 300 mg aspirin and continuing aspirin indefinitely.For patients with no contraindications, who may undergo PCI within 24 hours of admission to hospital, NICE recommends offering a 300 mg loading dose of clopidogrel. The guidance states that there is emerging evidence about the use of a 600 mg loading dose of clopidogrel for patients undergoing PCI within 24 hours of admission. However, NICE was not able to formally review all the evidence and was therefore unable to recommend this at the time of guidance publication (March 2010).
New evidence: The CURRENT-OASIS 7 trial (The Lancet Volume 376, Issue 9748) assessed whether doubling of the loading and maintenance dose of clopidogrel for 7 days was better than the standard dose and if high dose aspirin was better than low dose aspirin in patients undergoing PCI.A 7 day double dose clopidogrel regimen (600 mg on day 1, 150 mg on days 2 to 7, then 75 mg daily) was associated with a reduction in cardiovascular events and stent thrombosis compared to the standard dose (300 mg on day 1 then 75 mg daily). The analysis suggests a clear benefit in the 17,236 patients who underwent a PCI procedure.
Using the CURRENT/OASIS 7 trial definition, major bleeding was more common with double than standard dose clopidogrel. Before PCI, rates of ischaemic events or major bleeding did not differ between the groups.The researchers conclude that a double-dose clopidogrel regimen (600 mg loading dose) can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended early PCI.Efficacy and safety did not differ between high dose (300 to 325 mg daily) and low dose (75 to 100mg daily) aspirin. However, since the dose comparison was for only 30 days, use of low-dose aspirin is still thought to be reasonable for long-term therapy.
New evidence: The CURRENT-OASIS 7 trial (The Lancet Volume 376, Issue 9748) assessed whether doubling of the loading and maintenance dose of clopidogrel for 7 days was better than the standard dose and if high dose aspirin was better than low dose aspirin in patients undergoing PCI.A 7 day double dose clopidogrel regimen (600 mg on day 1, 150 mg on days 2 to 7, then 75 mg daily) was associated with a reduction in cardiovascular events and stent thrombosis compared to the standard dose (300 mg on day 1 then 75 mg daily). The analysis suggests a clear benefit in the 17,236 patients who underwent a PCI procedure.
Using the CURRENT/OASIS 7 trial definition, major bleeding was more common with double than standard dose clopidogrel. Before PCI, rates of ischaemic events or major bleeding did not differ between the groups.The researchers conclude that a double-dose clopidogrel regimen (600 mg loading dose) can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended early PCI.Efficacy and safety did not differ between high dose (300 to 325 mg daily) and low dose (75 to 100mg daily) aspirin. However, since the dose comparison was for only 30 days, use of low-dose aspirin is still thought to be reasonable for long-term therapy.
Commentary:"CURRENT-OASIS 7 is the latest in a long list of trials that tests the impact of dual anti-platelet therapy on efficacy, and since most trials look at the effect of increased therapy to prevent stent thrombosis (or its surrogate acute myocardial infarction/death), also importantly bleeding. A number of studies and retrospective analyses of large trials have shown the benefit of 600 mg over 300 mg.
"I see two problems with this study. First, two things were changed at once (so we don't really know which change, aspirin or clopidogrel, was beneficial in this study) and secondly, increasing the loading dose of clopidogrel to 150 mg with maintenance of 150 mg, if this is thought to be of value (and the trial suggests it might be), was associated with extra bleeding risk.
"So how should we use this study as applied to UK practice? In patients presenting with acute coronary syndrome who are at a low risk of bleeding (i.e. normal renal function, body weight of more than 60kg and no evidence of GI tract disease), it might be reasonable to give 600 mg clopidogrel loading but then to increase the maintenance clopidogrel dose to 150 mg for one week (only) and to maintain the patient on 75 mg aspirin and 75 mg clopidogrel." - Tony Gershlick, Professor of Interventional Cardiology, University of Leicester.
"I see two problems with this study. First, two things were changed at once (so we don't really know which change, aspirin or clopidogrel, was beneficial in this study) and secondly, increasing the loading dose of clopidogrel to 150 mg with maintenance of 150 mg, if this is thought to be of value (and the trial suggests it might be), was associated with extra bleeding risk.
"So how should we use this study as applied to UK practice? In patients presenting with acute coronary syndrome who are at a low risk of bleeding (i.e. normal renal function, body weight of more than 60kg and no evidence of GI tract disease), it might be reasonable to give 600 mg clopidogrel loading but then to increase the maintenance clopidogrel dose to 150 mg for one week (only) and to maintain the patient on 75 mg aspirin and 75 mg clopidogrel." - Tony Gershlick, Professor of Interventional Cardiology, University of Leicester.
For more evidence relating to cardiovascular health visit NHS Evidence - Cardiovascular.
NICE guidance on the early management of unstable angina and non ST segment elevation myocardial infarction is due to be updated in March 2013.
Eyes on Evidence helps contextualise significant new evidence, highlighting areas that could signal a change in clinical practice. It does not constitute formal NICE guidance. The commentaries included are the opinions of contributors and do not necessarily reflect the views of NICE.
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