Data from the SMART-DATE study indicate that acute coronary syndrome patients who receive short-term (six months) dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) have a significantly increased risk of myocardial infarction compared with those who receive it for 12 months or longer. The study investigators report that these findings mean that they “cannot conclude” short-term DAPT is safe in patients with acute coronary syndromes.
Writing in The Lancet, Joo-Yong Hahn (Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, South Korea) and colleagues explain that they conducted the trial because, at present, identifying the optimal duration of DAPT after PCI in acute coronary syndrome patients is “challenging”. They note that while a recent network meta-analysis suggested short-term DAPT was not associated with higher rates of myocardial infarction or stent thrombosis, most of the patients enrolled in that study “had a relatively low risk and the proportion of patients with myocardial infraction was at about 10%”. “Therefore, we sought to investigate whether a reduced six-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT at 18 months after current-generation drug-eluting stent implantation in patients with a broad spectrum of acute coronary syndrome,” the authors comment.
Overall, 2,712 patients were enrolled; of these, 1,357 were randomised to receive six-month DAPT and 1,355 were randomised to receive 12-month DAPT or longer. In each group, approximately 38% had ST-segment elevation myocardial infarction (STEMI), 31% had non-STEMI (NSTEMI), and 31% had unstable angina. Additionally, in each group, a third of patients received an everolimus-eluting stent, a third received a zotarolimus-eluting stent, and a third received a biolimus-eluting stent. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction, or stroke.
At 18 months, there was no significant difference in the primary endpoint between groups: 4.7% for six-month DAPT vs. 4.2% for 12-month DAPT (p for non-inferiority; p=0.03). However, Hahn et al comment that the non-inferiority of margin of 2% “seemed to be wide considering that the actual rate of the primary endpoint was 4.2% with 12-month DAPT or longer DAPT”.
Additionally, myocardial infarction occurred significantly more frequently in the six-month DAPT group than in the 12-month group: 1.8% vs. 0.8%, respectively; p=0.02. To further explore this increased risk, Hahn et al performed a post-hock landmark analysis of the primary endpoint and this showed that the risk of MACCE between six months and 18 months “seemed be higher” in the six-month DAPT group (p=0.07). Looking at the individual endpoints of this primary outcome, they found that there were no significant differences in the risk of all-cause death between groups “but myocardial infarction occurred more frequently in the six-month DAPT group than in the 12-month or longer DAPT group (p=0.01 for the difference)”. The risk of cardiac death or myocardial infarction was also significantly higher in the six-month DAPT group.
As to why the risk of myocardial infarction was higher in the six-month DAPT group, Hahn et al state that the “most plausible explanation” might be an increase in stent thrombosis in that group after cessation of DAPT but they note that there was not a significant difference in stent thrombosis between groups. The authors add that while their sample size was too small to detect significant differences in events occurring at a low rate (such as stent thrombosis), “exclusive use of a second-generation drug-eluting stent with proven efficacy and safety might explain the absence of a significant difference in the rate of stent thrombosis between the two groups”. On the other hand, there was a strong trend of an increased risk of myocardial infarction in the non-target vessel (p=0.07), which may be the major cause of increased risk of myocardial infarction in the six-month group.
On the basis of their results, Hahn et al state: “We cannot conclude that short-term DAPT is safe in patients with acute coronary syndrome undergoing PCI with current-generation drug-eluting stents.” They add that, as they did not observe definite harm from prolonged DAPT in terms of mortality or major bleeding, “12-month or longer DAPT should remain the standard of care for these patients despite the improve safety of current-generation drug-eluting stents”.
The findings of SMART-DATE differ from the recent DAPT STEMI trial. This study did not find a significant difference in the rate of all-cause mortality, myocardial infarction, any revascularisation, stroke or major bleeding at 18 months between STEMI patients who received DAPT for six months after PCI and those received it for 12 months. All patients in that study underwent PCI with a second-generation zotarolimus-eluting stent.
However, in DAPT STEMI, patients were randomised to aspirin monotherapy or additional six-month after receiving DAPT for six months (and being event free)—i.e. unlike SMART-DATE, patients were not randomised at baseline. Additionally, the investigator of that study Elvin Kedhi (Isla Hartcentrum, Zwolle, The Netherlands) did note that further data were needed to confirm the safety and efficacy of short-term DAPT after PCI in STEMI patients.
According to Hyeon-Cheol Gwon (Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, South Korea), the corresponding author of the SMART-DATE paper, both DAPT-STEMI and the REDUCE trial (which had similar findings) were underpowered to test the rate of MACCE. He comments: “They adopted revascularisation and bleeding as a part of the primary endpoint, mostly due to small sample size, whereas SMART-DATE trial is the first trial powered to test MACCE.”
Gwon presented the results of the SMART-DATE study during a late-breaking trial session of the 2018 American College of Cardiology Scientific Session (ACC; 10–12 March, Orlando, USA).
