The Dual Antiplatelet Therapy (DAPT) trial included patients with cardiovascular disease who underwent a coronary stent procedure in which a drug-eluting stent was placed. All received dual antiplatelet therapy (aspirin plus clopidogrel or prasugrel) for the first 12 months, after which they were randomised to continue this, or to revert to aspirin alone (plus placebo) for a further 18 months. This is the first randomised study in this area to be sufficiently powered to assess the effect of DAPT on hard clinical endpoints.
The co-primary efficacy endpoints were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. Continued DAPT was associated with a reduction in stent thrombosis (0.4% vs. 1.4%; HR 0.29; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; HR 0.71; P<0.001). It was however unexpectedly associated with an increase in overall mortality (2.0% in DAPT group and 1.5% in placebo group; HR 1.36, 95% CI 1.00 to 1.85; P=0.05), which was largely due to non-cardiovascular causes, primarily cancer and trauma deaths. Of note, bleeding events did not arise in the majority of the non-cardiovascular deaths and did not entirely account for the differences in mortality between the groups. The rate of moderate or severe bleeding was also increased (2.5% vs. 1.6%; P=0.001).
The US FDA has issued a Drug Safety Communication following the publication of this study, which can be viewed at the link below. The FDA will evaluate the results from this trial with other available data and will communicate its final conclusions when this is complete. In the meantime the Agency believes that the benefits of clopidogrel and prasugrel continue to outweigh their risks, and they advise healthcare professionals not to change the way they prescribe them at this time. No information from the MHRA is available at the current time.
The authors of an accompanying editorial comment that the observed increase in moderate or severe bleeding, as well as the possible increase in all-cause mortality, leads to uncertainty regarding the incremental benefit from prolonging DAPT. As the study only included patients who had not had a major adverse cardiovascular or cerebrovascular event, repeat revascularisation, or moderate or severe bleeding by the completion of 12 months of DAPT and who were adherent to thienopyridine therapy, it may have excluded the very patients who would have benefited the most from prolonged treatment. They say that the key message of the study is the suggestion that some patients who have been treated with a drug-eluting stent may benefit from extending DAPT beyond 1 year, but also that the potential harm with this approach should not be overlooked. Moreover, it is not known how long this benefit extends and which patients benefit most. The safest and most effective duration of DAPT therefore remains uncertain and should be individualised for each patient.
A meta-analysis of 14 trials (including the DAPT study) did not find any difference between extended duration and short-duration DAPT (≤6 months) or aspirin alone in terms of all-cause, cardiovascular or non- cardiovascular mortality. Please see the link below for further details.