ORLANDO — Although a shorter duration of dual antiplatelet therapy (DAPT) was non-inferior to the standard regimen among acute coronary syndrome (ACS) patients getting drug-eluting stents (DES) in the SMART-DATE trial, a signal of excess MIs led investigators to caution against the interpretation that the two are equally safe.
Overall protection against recurrent ischemic events in the 18 months after percutaneous coronary intervention (PCI) — namely combined all-cause mortality, MI, and cerebrovascular events — was about the same whether ACS patients got 6 months or 12 months of DAPT (4.7% vs 4.2%, HR 1.13, 95% CI 0.79-1.62, P=0.027 for non-inferiority).
No difference was observed in the individual endpoints of all-cause death, stent thrombosis, and bleeding, an intention-to-treat analysis showed. However, MI turned out to be more likely with 6-month DAPT (1.8% vs 0.8%, P=0.02), Hyeon Cheol Gwon, MD, of Samsung Medical Center in South Korea, said at a late-breaking trial session at the American College of Cardiology (ACC) annual meeting. The findings were simultaneously published in the Lancet.
The MI difference was no longer significant on per-protocol analysis (1.6% vs 0.8%, P=0.10), they reported. Still, “although the non-inferiority of the 6-month DAPT to 12-month or longer DAPT was met, the increased MI risk with 6-month DAPT prevent us from concluding that short-term DAPT is safe in ACS patients undergoing PCI with current-generation DES,” the investigators emphasized.
“Prolonged DAPT in ACS patients without excessive risk of bleeding should remain the standard of care,” they said, noting that 12 months of DAPT is currently recommended for this population.
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Close to 60% of MIs were found in the target vessel during index PCI.
“It’s interesting that you met the primary endpoint, but you are advising against change in practice,” said ACC session panelist Roxana Mehran, MD, of Mount Sinai School of Medicine in New York City.
Gregg Stone, MD, of Columbia University Medical Center/New York-Presbyterian Hospital, added that the findings are similar to those of the REDUCE trial in which shorter DAPT was tied to “strong trends” in death and stent thrombosis among patients receiving the Combo sirolimus-eluting bioresorbable polymer stent.
SMART-DATE had 2,712 ACS patients randomized to one of the two DAPT regimens across 31 centers in South Korea. This cohort had also been randomized to PCI with the zotarolimus-eluting Resolute Integrity, everolimus-eluting Xience Prime, or biolimus A9-eluting BioMatrix Flex stents.
Excluded populations were those with recent major bleeding and prior DES implantation within a year, for example.
The 6-month DAPT group adhered to their assignment treatment in 73.7% of cases, while the 12-month group did so in 95.7%. Having so many crossovers in the former was a major limitation of the open-label trial, Gwon acknowledged.
“These are difficult trials to perform,” Stone noted, adding that here there is a methodological issue that is common in these types of studies. By randomizing patients before the actual switch in DAPT duration, “anything that happens in 6 months just adds noise,” he said. “The optimal way is to randomize at 6 months.”
Nonetheless, the present findings appear to refute the sentiment that older stents were guiding guidelines on DAPT duration and that things would be different with newer DES, according to Dipti Itchhaporia, MD, of Hoag Memorial Hospital Presbyterian in Newport Beach, California.
“It’s nicely shown with the risk of MI in 6-month DAPT that [newer DES are] not enough to make us feel comfortable. The ACS patient is fundamentally a different kind of patient,” she said at an ACC press conference.
SMART-DATE was funded by Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors, and Dong-A ST.
Gwon disclosed relevant relationships with Medtronic, Abbott, and Boston Scientific.