6-Month Versus 12-Month or Longer Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome (SMART-DATE): A Randomised, Open-label, Non-inferiority Trial

Trial Reference

Hahn JY, Song YB, Oh JH, et al; SMART-DATE investigators. 6-Month Versus 12-Month or Longer Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome (SMART-DATE): A Randomised, Open-label, Non-inferiority Trial. Lancet. 2018 Mar 9. pii: S0140-6736(18)30493-8. [Epub ahead of print]

Abstract | Full Text

Expert Comment

Professor Albert Ferro, Professor of Cardiovascular Clinical Pharmacology, King’s College London.

In patients with acute coronary syndrome, who undergo insertion of a drug-eluting stent (which is the standard type of stent used in percutaneous coronary intervention nowadays), the standard of care is to give dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor for 12 months, following which aspirin is given alone long-term. This trial, in 31 centres in South Korea, examined whether 6 months of DAPT would be non-inferior to 12 months or longer. 2,712 patients were randomised to receive either 6 months (n=1,357) or ≥ 12 months (n=1,355) of DAPT (clopidogrel was used as the P2Y12 inhibitor in around 80% of cases in both groups, since the newer agents were not available in South Korea at the beginning of the study). The primary endpoint, a composite of all-cause death, myocardial infarction or stroke at 18 months post-procedure, was similar in the 6- versus the ≥ 12-month group (4.7% vs 4.2%; HR 1.13; 95% CI 0.79-1.62), meeting the definition of non-inferiority in this population (P = 0.027). Neither all-cause mortality nor stroke differed between the study arms, but the rate of myocardial infarction was significantly higher for patients randomized to 6 versus 12 months of DAPT (1.8% vs 0.8%; 95% CI 1.15-5.05). There was a trend toward decreased bleeding with shorter DAPT, but this did not reach significance.

Conclusion

The authors conclude that “The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation drug-eluting stents.” This seems an entirely justified conclusion. The intensity and duration of antiplatelet therapy has to strike a balance between adequate prevention of thrombosis and avoidance of excessive bleeding. Numerous trials have shown beyond doubt that DAPT offers protection over and above single antiplatelet therapy in patients undergoing coronary stent insertion; however, the optimal duration of DAPT has been hotly debated, and it had been hoped that a shorter duration would give rise to similar cardioprotection whilst reducing the bleeding risk.

SMART-DATE, on the other hand, has shown that there is at least a suggestion of increased thrombotic events in the shorter duration group, and that there is no significant reduction in bleeding. With a significant increase in the secondary endpoint of myocardial infarction and the wide non-inferiority margin that was set, it cannot be concluded that shorter duration DAPT is as safe as longer. It is also noteworthy that there was crossover between the study arms, with just 73.7% and 95.7% of patients assigned to short- and long-term DAPT, respectively, adhering to the study protocol; given the high rate of crossover in the 6-month group, this may have led to an underestimation of the difference between the groups, again calling into question the equi-effectiveness of the two treatment regimes.

In patients where bleeding risk is a real concern, shorter duration DAPT, for example 6 months, can certainly be considered, as shown by the DAPT-STEMI and REDUCE trials. But in those patients where bleeding risk is judged not to be excessive, SMART-DATE suggests that it seems prudent to continue DAPT for at least 12 months in these patients. Further dedicated studies need to be done to re-examine this question in patients receiving the newer P2Y12 inhibitors prasugrel and ticagrelor, since they will carry an increase both in efficacy and in bleeding complications as compared with clopidogrel.

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