- Use of dual antiplatelet therapy (DAPT) for secondary prevention of stroke provides better protection than monotherapy in the first 3 months; however, short-term DAPT also carries an increased risk for bleeding.
Why this matters
- There is uncertainty regarding the optimal duration of DAPT for the secondary prevention of stroke.
- The American Heart Association/American Stroke Association guidance supports the use of DAPT for 21 days or for a duration of up to 90 days from the onset of symptoms; however, the class of recommendation and level of evidence are moderate.
- The NICE guidance in the UK vaguely states that individuals with an ischaemic stroke or transient ischaemic attack (TIA) should receive clopidogrel or dipyridamole in monotherapy or in combination with aspirin (DAPT), and that treatment may be continued until and patients and their clinicians consider it appropriate to stop.
- Network meta-analysis of 16 randomised controlled trials with a total of 55,261 patients.
- Primary efficacy outcome was the prevention of recurrent stroke.
- Secondary outcomes included prevention of ischaemic stroke, all bleeding, severe bleeding, all-cause mortality, cardiovascular mortality and myocardial infarction.
- Funding: National Institute for Health Research, UK.
- Short-term DAPT with aspirin clopidogrel was associated with a lower recurrence of stroke vs aspirin (OR, 0.67; 95% CI, 0.58-0.77); however, the association was only borderline significant for long-term aspirin clopidogrel vs aspirin (OR, 0.84; 95% CI, 0.70-1.01).
- Short-term aspirin clopidogrel was associated with decreased ischaemic stroke vs aspirin (OR, 0.68; 95% CI, 0.58-0.79). Long-term aspirin clopidogrel was more effective than aspirin in reducing ischaemic stroke (OR, 0.79; 95% CI, 0.65-0.96), but not more than clopidogrel (OR, 0.92; 95% CI, 0.79-1.08).
- Aspirin-clopidogrel DAPT was associated with an increase in all bleeding:
- Long-term aspirin clopidogrel vs clopidogrel: OR, 2.77; 95% CI, 2.21-3.46.
- Long-term aspirin clopidogrel vs aspirin: OR, 2.25; 95% CI, 1.97-2.57.
- Short-term aspirin clopidogrel vs aspirin: OR, 1.76; 95% CI, 1.26-2.46.
- Short-term aspirin clopidogrel was associated with an increase in severe bleeding vs aspirin (OR, 2.13; 95% CI, 1.14-3.98). Long-term aspirin clopidogrel vs clopidogrel showed a similar association (OR, 1.99; 95% CI, 1.40-2.81).
- No differences were observed in the outcomes of all-cause death, cardiovascular death and myocardial infarction.
- In the network meta-analysis, short-term aspirin clopidogrel ranked best for reducing stroke (85.7% probability) and ranked fourth for preventing all bleeding (37.9%). Long-term aspirin clopidogrel ranked second for efficacy (40.4%) and worst for safety (98.0%).
- Longer follow-up studies in patients receiving short-term DAPT were not available.
- Monotherapy was assumed to be inferior to DAPT.
- No comparisons were made between monotherapies or long vs short monotherapy.
- Potential biases and heterogeneity among studies.