Stepwise DAPT de-escalation on par with standard therapy in patients with ACS

A stepwise dual antiplatelet therapy (DAPT) de-escalation strategy among patients with acute coronary syndrome (ACS) who could be treated by paclitaxel-coated balloons without stents demonstrates noninferiority to the standard 12-month DAPT for all net adverse clinical events, according to a study.

A total of 1,948 adults with ACS across 41 hospitals in China between 27 November 2021 and 21 January 2023 were included. Of these, 975 were randomized to the stepwise DAPT de-escalation therapy group (aspirin plus ticagrelor for 1 month, followed by 5 months of ticagrelor monotherapy, then 6 months of aspirin monotherapy) and 973 to the standard DAPT group (aspirin plus ticagrelor for 12 months).

ACS patients had a mean age of 59.2 years, and the majority (74.9 percent) were men. Some 30.5 percent of participants had diabetes, and 20.6 percent had a high risk of bleeding. Among the treated lesions, 60.9 percent were in small vessels and 17.8 percent were in-stent restenosis. The coated balloon had a mean diameter of 2.72 mm. [BMJ 2025;388:e082945]

Net adverse clinical events (ie, all-cause death, stroke, myocardial infarction [MI], revascularization, and Bleeding Academic Research Consortium [BARC] type 3 or 5 bleeding) at 12 months occurred in 87 (8.9 percent) patients in the stepwise de-escalation group and 84 (8.6 percent) in the standard group (difference, 0.36 percent, upper boundary of the one-sided 95 percent confidence interval [CI], 2.47; p=0.013 for noninferiority).

BARC type 3 or 5 bleeding occurred in four patients in the stepwise de-escalation group and 16 in the standard group (0.4 percent vs 1.6 percent; difference, –1.19 percent, 95 percent CI, –2.07 to –0.31; p=0.008), while all-cause death, stroke, MI, and revascularization occurred in 84 and 74 participants, respectively (8.6 percent vs 7.6 percent; difference, 1.05 percent, 95 percent CI, –1.37 to 3.47; p=0.396).

When applying the win ratio method, the stepwise de-escalation therapy achieved “more wins” than the standard regimen (14.4 percent vs 10.1 percent) for the predefined hierarchical composite endpoint of all-cause death, stroke, MI, revascularization, BARC type 3 bleeding, and BARC type 2 bleeding (win ratio, 1.43, 95 percent CI, 1.12—1.83; p=0.004).

These findings were consistent in the per-protocol and the intention-to-treat analyses.

Disparity

In the intention-to-treat population, the stepwise de-escalation group showed a 1-percent higher rate of patient-oriented composite endpoint and a 1-percent lower rate of BARC type 3 or 5 bleeding than the standard group, suggesting a trade-off between ischaemic and bleeding risks.

"However, participants who were not adherent to the study protocol were also included in the intention-to-treat population,” the researchers said.

On the other hand, the per-protocol analyses revealed no difference in patient-oriented composite endpoint between the strictly ticagrelor-based stepwise DAPT de-escalation therapy and the standard 12-month DAPT (8.1 percent vs 8.3 percent). Moreover, the stepwise de-escalation group maintained a significantly lower incidence of BARC type 3 or 5 bleeding.

“This disparity between intention-to-treat and per protocol populations was primarily caused by the inclusion or exclusion of patients on clopidogrel-based monotherapy,” the researchers said. 

“As such, we considered that the 1-percent higher risk of patient-oriented composite endpoint in the intention-to-treat population might be due to the lower potency of clopidogrel-based monotherapy compared with protocol-defined ticagrelor-based monotherapy,” they added. [JAMA Cardiol 2022;7:407-417]

“This finding also underscores the importance of adhering to ticagrelor to uphold the efficacy of a P2Y12 inhibitor monotherapy-based stepwise DAPT de-escalation approach, especially in patients with higher thrombotic risks,” according to the researchers. [JACC Asia 2022;2:1-18]