The study can’t supplant an RCT in this space, but does provide clear support for both short DAPT and P2Y12 inhibitors post-ACS.
The benefits of limiting dual antiplatelet therapy (DAPT) to a short course after PCI for acute coronary syndromes vary depending on the type of monotherapy used afterward, according to a new network meta-analysis.
Among more than 45,000 patients enrolled in 23 international studies, P2Y12 inhibitor monotherapy reduced both net adverse clinical events (NACE) and any bleeding compared with aspirin monotherapy. Additionally, compared with standard DAPT, only P2Y12 inhibitor monotherapy reduced both NACE and any bleeding, whereas aspirin did neither. Notably, the analysis showed no significant difference in NACE for short DAPT overall compared with standard DAPT.
The study shows that “short DAPT, in general, is a good option for patients with acute coronary syndromes if they don’t have excess thrombotic risk,” senior author Davide Capodanno, MD, PhD (University of Catania, Italy), told TCTMD. But one potential reason why the study didn’t show an overall benefit with less than 12 months of DAPT in this population “is because of the aspirin monotherapy after DAPT,” he added. “If we could continue the P2Y12 inhibitor monotherapy, that would be better.”
The analysis can’t compare to a randomized trial in this space—something Capodanno says is needed for ACS patients, who are currently treated with a “one-size-fits-all” strategy of 12-month DAPT—but it provides further rationale for one. “Within this population, there are patients who are at high bleeding risk and they have different combinations of thrombotic and bleeding risk, so it’s likely that we need to personalize in this population, specifically,” he said.
It’s likely that we need to personalize in this population. Davide Capodanno
Commenting for TCTMD, Marco Valgimigli, MD, PhD (Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland), agreed that the results suggest using P2Y12 inhibitor monotherapy instead of aspirin when a short course of DAPT is selected in this population. “However, I am not 100% sure the results that the authors are coming out with are the real ones,” he added as a caveat. “I think the P2Y12 inhibitor should be preferred because of the lower risk of subsequent NACE, not because of a clear bleeding advantage, which has never been reported by direct comparisons.”
The findings were published in the August 11, 2025, issue of JACC: Cardiovascular Interventions with Claudio Laudani, MD (University of Catania), as the first author.
Fewer NACE, Less Bleeding
For the meta-analysis, the researchers included 45,394 patients (51,568 patient-years; mean age 63 years; 23% women) from 23 trials with median DAPT durations of 4.8 and 2.2 months in those studying aspirin (n = 14) and P2Y12 inhibitor monotherapy (n = 9), respectively.
The risk of NACE was lower with P2Y12 inhibitor monotherapy compared with standard DAPT (incidence rate ratio [IRR] 0.78; 95% CI 0.64-0.95), but this was not seen with aspirin monotherapy versus standard DAPT (IRR 1.03; 95% CI 0.89-1.18; P = 0.026 for interaction). The findings were similar when looking at any bleeding for P2Y12 inhibitor monotherapy (IRR 0.56; 95% CI 0.46-0.67)—where there was also a significant reduction in major bleeding—compared with aspirin alone (IRR 0.84; 95% CI 0.66-1.06; P = 0.008 for interaction).
In a pooled analysis, the researchers found only a nonsignificant NACE reduction for short DAPT overall compared with standard DAPT. However, there were significant drops in both any and major bleeding with less than 12 months of DAPT.
In an indirect comparison, P2Y12 inhibitor monotherapy significantly reduced the risk of both NACE (IRR 0.77; 95% CI 0.62-0.95) and any bleeding (IRR 0.68; 95% CI 0.48-0.95) compared with aspirin monotherapy.
“Now it’s time for the comparison of monotherapies,” Capodanno said, noting that both SMART-CHOICE 3 and HOST-EXAM have compared clopidogrel and aspirin, but only in the “remote” period after PCI when the overall thrombotic risk is lower for patients. “What would be nice is to have a trial of P2Y12 inhibitor monotherapy versus aspirin for 3 to 6 months in patients with acute coronary syndromes to see whether there is, of course, a benefit of P2Y12 inhibitor monotherapy versus aspirin as well,” he suggested. “This is a kind of design that could clarify finally whether this is really a strategy that deserves better recommendation as compared with the standard of care.”
Valgimilgi, too, said the field needs a “direct comparison” of aspirin versus P2Y12 inhibitor monotherapy after DAPT discontinuation. “And we need to convince the people that the short DAPT regimen is the way forward,” he urged. “This is something I would like to emphasize. Whatever the type of monotherapy you’re going to choose, you have to go for a short DAPT regimen.”
Whatever the type of monotherapy you’re going to choose, you have to go for a short DAPT regimen. Marco Valgimigli
In an accompanying editorial, Giuseppe Gargiulo, MD, PhD (Federico II University of Naples, Naples, Italy), and colleagues write that “the actual superiority of short DAPT compared with standard DAPT in ACS, and even more the superiority of P2Y12 inhibitor monotherapy compared with aspirin monotherapy, should be interpreted with caution.”
Still, they continue, “we agree with the investigators’ conclusion that this meta-analysis can be useful for clinicians and future guidelines on the relative merits of the available antiplatelet monotherapy strategies, allowing a personalized approach depending on the ischemic and bleeding risk balance.”