- an expert panel produced a strong recommendation for initiating dual antiplatelet therapy within 24 hours of the onset of symptoms, and for continuing it for 10-21 days. Current practice is typically to use a single drug (1,2,3)
- dual antiplatelet therapy (DAPT) with clopidogrel and aspirin (acetylsalicylic acid) during the first 21 days after the index event reduced the risk of recurrent major ischaemic events compared with aspirin monotherapy
- DAPT should be used in the first 24 hours after a high risk transient ischaemic attack or minor ischaemic stroke
- DAPT is considered too risky after major stroke and the panel suggests that major strokes, as opposed to minor ones, are treated with single agent only because of the higher risk of haemorrhagic transformation.
Overall, the panel was confident that DAPT, when started within 24 hours of symptom onset and used for 10-21 days (2) - if used after a high risk transient ischaemic attack or minor ischaemic stroke:
- reduces non-fatal recurrent stroke (ischaemic and haemorrhagic) in the first 90 days by 1.9% (high quality evidence)
- reduces the incidence of moderate or severe functional disability by 1.4% (moderate quality evidence)
- reduces the incidence of poor quality of life by 1.3% (moderate quality evidence)
However, DAPT has little or no impact on:
- all-cause mortality (moderate quality evidence).
- incidence of myocardial infarction or recurrent transient ischaemic attack (moderate quality evidence).
Furthermore, DAPT also has some harms:
- a small (0.2%), possibly important increase in moderate to major extracranial bleeding events (moderate quality evidence)
- a small increase in the risk of minor extracranial bleeding events by 0.7% (high quality evidence).
Duration of DAPT with clopidogrel and aspirin
The panel was confident that DAPT given for 10-21 days compared with 22-90 days results in:
- absolute risk decrease of 0.4% in recurrent ischaemic stroke (moderate quality evidence of no benefit on stroke reduction with prolonged clopidogrel)
- absolute risk decrease of 0.3% in moderate to major bleeding events (high quality evidence).
The maximum benefit occurred in the first 10 days.
Doses in DAPT
- for clopidogrel - a loading dose of 300 mg and a dose of 75 mg thereafter seem reasonable (2)
- for aspirin -a dose between 75 mg and 345 mg seems reasonable
- some clinicians may prefer to prescribe at the low end of this range to minimise harm
Notes:
- recommendations (2) guideline are based on a linked systematic review (1) triggered by a randomised controlled trial published in the New England Journal of Medicine in August 2018 (3)
Reference:
- Hao Q, Tampi M, O'Donnell M, Foroutan F, Siemieniuk RAC, Guyatt G. Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis. BMJ 2018;363:k5108. 10.1136/bmj.k5108.
- Prasad K et al. Dual antiplatelet therapy with aspirin and clopidogrel for acute high risk transient ischaemic attack and minor ischaemic stroke: a clinical practice guideline. BMJ 2018;363:1-11.
- Johnston SC, Easton JD, Farrant M, etal. Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med 2018;379:215-25.