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The optimal management of dual antiplatelet therapy (DAPT) in patients presenting with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) remains a dynamic and evolving area. Striking a delicate balance between ischemic protection and the risk of bleeding complications is the key challenge.¹ Randomized controlled trials (RCTs), including patients with ACS requiring PCI, have almost consistently demonstrated that reduced DAPT durations are not associated with increased rates of ischemic events.² Notably, compared with standard DAPT, the patients assigned to short DAPT durations experienced much less major bleeding.² The assessment of DAPT in RCTs has progressively involved shorter durations (1-to-3 months of DAPT) followed by P2Y12 inhibitor monotherapy, compared with standard 12-month DAPT.³ Against this background and in light of the substantial advance in stent technology and procedural optimization, it has been proposed that stopping aspirin at discharge and continuing potent P2Y12 inhibitor monotherapy may be as safe and effective as standard prolonged DAPT for patients admitted for ACS who were successfully revascularized by PCI without significant residual coronary artery disease.

The NEO-MINDSET (Percutaneous Coronary Intervention Followed by Antiplatelet Monotherapy in the Setting of Acute Coronary Syndromes) study investigated the effects of immediate postprocedural aspirin withdrawal in patients taking DAPT who underwent PCI for ACS.⁴ The study involved 3,400 patients within the first 4 days of hospitalization following a successful PCI, who were randomly assigned to either discontinuation of aspirin and continuation of a potent P2Y12 inhibitor monotherapy (ticagrelor or prasugrel) or to receive DAPT that included aspirin and a potent P2Y12 inhibitor for 12 months. The primary endpoint events (death from any cause, myocardial infarction [MI], stroke, or urgent revascularization) occurred in 7% of patients in the monotherapy group and 5.5% in the DAPT group (p_{noninferiority} = 0.11). Major or clinically relevant nonmajor bleeding occurred in 2% of patients in the monotherapy group and 4.9% of patients in the DAPT group, and stent thrombosis occurred in 0.7% and 0.2% in the matched groups. These findings indicate that immediate P2Y12 inhibitor monotherapy with withdrawal of aspirin is not as protective as DAPT for ischemic events in patients with ACS after PCI, even though it does reduce bleeding. Whereas reductions in major bleeding despite numerically increased ischemic events may be appealing in patients at high bleeding risk (HBR), this trade-off appears less favorable in patients without HBR. Only one-fifth of patients in the NEO-MINDSET study were classified as at HBR. Ongoing trials, such as LEGACY (Less Bleeding by Omitting Aspirin in Non-ST-segment Elevation Acute Coronary Syndrome Patients), will likely shed light on unaddressed questions.⁵

The TARGET-FIRST (Evaluation of a Modified Anti-Platelet Therapy Associated With Low-dose DES Firehawk in Acute Myocardial Infarction Patients Treated With Complete Revascularization Strategy) trial included patients who had successfully undergone PCI with advanced drug-eluting stents within 7 days of MI and had completed 1 month of DAPT without ischemic complications or major bleeding. After randomization, patients were assigned to receive either P2Y12 receptor inhibitor monotherapy or DAPT for 11 months. P2Y12 inhibitor monotherapy was noninferior to DAPT for cardiovascular and cerebrovascular outcomes, and superior in reducing clinically relevant bleeding, supporting de-escalation in carefully selected patients at low risk.⁶ No previous RCT has assessed early aspirin discontinuation in patients with acute MI who achieve early, complete revascularization with modern stents. These results reflect the benefits of modern stents, high procedural success, and optimal medical therapy, making early aspirin discontinuation feasible in this select population.

The optimal antiplatelet therapy is not well established for patients who have undergone complex PCI procedures and are at high risk of ischemic events. The TAILORED-CHIP (TAILored Versus COnventional AntithRombotic StratEgy IntenDed for Complex HIgh-Risk PCI) trial included 2,018 patients with high-risk anatomical or clinical characteristics undergoing complex PCI.⁷ They were randomly assigned to receive either standard DAPT (clopidogrel plus aspirin for 12 months) or early escalation (low-dose ticagrelor at 60 mg twice daily plus aspirin for 6 months), followed by late de-escalation (clopidogrel monotherapy for 6 months). Overall results indicated that there was no significant difference between tailored therapy and standard DAPT in terms of the incidence of major ischemic events at 12 months. However, with tailored therapy, the incidence of clinically relevant bleeding was considerably higher. This finding challenges the notion that more is better even in carefully selected patients at high ischemic risk undergoing complex PCI procedures.

The ongoing theme across all trials is to strike a judicious balance between risks of ischemia and bleeding. The trend is toward personalized antiplatelet therapy, moving away from a one-size-fits-all approach. Patient risk profiles, including bleeding and ischemic risks, are crucial for determining the intensity and duration of therapy. It is critical to use bleeding risk scores and shared decision-making to help patients and clinicians weigh potential benefits and harms of different antiplatelet regimens. Despite emerging evidence for abbreviated DAPT in specific situations, 12 months of DAPT remains the default for most patients with ACS not at HBR, especially those who have undergone PCI.

References

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2. Valgimigli M, Landi A, Angiolillo DJ, et al. Demystifying the contemporary role of 12-month dual antiplatelet therapy after acute coronary syndrome. Circulation. 2024;150(4):317-335. doi:10.1161/CIRCULATIONAHA.124.069012
3. Giacoppo D, Matsuda Y, Fovino LN, et al. Short dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy vs. prolonged dual antiplatelet therapy after percutaneous coronary intervention with second-generation drug-eluting stents: a systematic review and meta-analysis of randomized clinical trials. Eur Heart J. 2021;42(4):308-319. doi:10.1093/eurheartj/ehaa739
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5. van der Sangen NMR, Küçük IT, Sivanesan S, et al. Less bleeding by omitting aspirin in non-ST-segment elevation acute coronary syndrome patients: rationale and design of the LEGACY study. Am Heart J. 2023;265:114-120. doi:10.1016/j.ahj.2023.07.011
6. Tarantini G, Honton B, Paradies V, et al. Early discontinuation of aspirin after PCI in low-risk acute myocardial infarction. N Engl J Med. Published online August 31, 2025. doi:10.1056/NEJMoa2508808
7. Kang DY, Wee SB, Ahn JM, et al. Temporal modulation of antiplatelet therapy in high-risk patients undergoing complex percutaneous coronary intervention: the TAILORED-CHIP randomized clinical trial. Eur Heart J. Published online August 31, 2025. doi:10.1093/eurheartj/ehaf652