Individualized DAPT de-escalation, guided by dynamic risk assessment using PRECISE‑DAPT and ARC-HBR criteria, optimizes net clinical benefit and should focus on precision antithrombotic strategies in Chinese populations and high-risk subgroups.
Abstract
Introduction Dual antiplatelet therapy (DAPT) is standard after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS), but prolonged DAPT increases bleeding risk, particularly in East Asian and high bleeding-risk (HBR) populations. De‑escalation strategies aim to balance ischaemic and bleeding risks. Methods We conducted a structured literature search in PubMed, EMBASE, and the Cochrane Library (January 2018–April 2026) for randomized trials and key studies on DAPT de-escalation in ACS patients after PCI, using the Academic Research Consortium (ARC) tripartite classification framework. Results Strong evidence supports discontinuation-based strategies: 3-month (TICO, TWILIGHT, SMART-CHOICE) and 1-month (ULTIMATE-DAPT, T-PASS, TARGET-FIRST) DAPT followed by P2Y12 inhibitor monotherapy reduce bleeding without increasing ischaemic events in selected patients. MASTER-DAPT established 1-month DAPT safety in HBR patients. However, very early aspirin withdrawal (within 4 days, NEO-MINDSET) failed non-inferiority for ischaemic outcomes, and clopidogrel monotherapy after 1-month DAPT was associated with higher ischaemic risk (STOPDAPT-2 ACS). Drug‑intensity de-escalation (e.g., ticagrelor-to-clopidogrel switching) and guided strategies using genotyping or platelet‑function testing show promise but require further validation. Conclusion Individualized DAPT de-escalation, guided by dynamic risk assessment using PRECISE‑DAPT and ARC-HBR criteria, optimizes net clinical benefit. Ticagrelor monotherapy after at least 1 month of DAPT is preferred over clopidogrel in ACS. Future research should focus on precision antithrombotic strategies in Chinese populations and high‑risk subgroups.
Antithrombotic therapy after percutaneous coronary intervention (PCI) is shifting from fixed 12‐month dual antiplatelet therapy (DAPT) to risk‐stratified, patient‐centered regimens. In this systematic review (80 studies; >330,000 patients), we compare personalized versus fixed DAPT strategies, evaluate abbreviated DAPT in high‐bleeding‐risk (HBR) populations, and evaluate bleeding and ischemic risk scores. Personalized strategies, including genotype‐guided therapy, ultra‐short DAPT (≤1 month) with P2Y12 monotherapy, and 3‐month DAPT, substantially reduce bleeding (often by roughly 25%−65%); ischemic risk after de‐escalation is heterogeneous across populations and strategies, with most trials showing neutrality and one (STOPDAPT‐2 ACS) signaling increased myocardial infarction (MI) when aspirin was withdrawn after 1–2 months of clopidogrel‐based DAPT in acute coronary syndrome (ACS). In HBR patients, 1 to 3‐month DAPT followed by P2Y12 monotherapy lowers major bleeding by up to 65% and may reduce cardiovascular mortality, without increased MI or stent thrombosis in most trials, although ischemic signals varied by population and strategy. In atrial fibrillation, avoiding prolonged triple therapy reduces bleeding by approximately 30%. In ACS, prasugrel is favored over ticagrelor for ischemic outcomes; ARC‐HBR, PRECISE‐DAPT, and the newer PRECISE‐HBR scores show moderate discrimination (c‐statistic 0.64–0.75). Contemporary data therefore support replacing one‐size‐fits‐all 12‐month DAPT with risk‐guided algorithms for post‐PCI antithrombotic therapy.
Thierry Kochkarian, Anis Ismail, Omar Chaabo et al.· Catheterization and cardiova...· 0 citations
BACKGROUND
Patients at high bleeding risk (HBR) presenting with acute coronary syndrome (ACS) and treated with percutaneous coronary intervention (PCI) have competing hazards of ischemic and bleeding events. In unselected ACS populations, trials of unguided de-escalation of P2Y12 inhibition reduce bleeding without excess ischemia; however, HBR patients were largely underrepresented in these studies. Comparative evidence across multiple de-escalation regimens in this vulnerable cohort is currently lacking.
STUDY DESIGN
DESC-HBR is a prospective, multicenter, randomized, open-label trial with blinded endpoint adjudication enrolling 200 HBR patients (PRECISE-DAPT ≥25 or ARC-HBR criteria) at 30 ± 7 days after ACS-PCI. Following one month of dual antiplatelet therapy (DAPT) with prasugrel 10 mg once daily or ticagrelor 90 mg twice daily, on a background of aspirin 100 mg, patients are randomized (1: 1:1:1) to clopidogrel 75 mg once daily, prasugrel 5 mg once daily, ticagrelor 60 mg twice daily, or continuation of full-dose potent therapy. The primary endpoint is the proportion of patients achieving optimal platelet reactivity (VerifyNow PRU 85-208) at 14 ± 2 days post-randomization, 2-h after maintenance dose. Key secondary outcomes include BARC bleeding, net adverse clinical events, quality of life and adherence. Pharmacodynamic profiling incorporates VerifyNow and Total Thrombus Formation Analysis (T-TAS). A total sample of 200 patients allows >80% power to detect superiority of each de-escalation arm versus control (α = 0.017).
CONCLUSIONS
DESC-HBR is the first randomized trial directly comparing multiple P2Y12 inhibitor de-escalation strategies in HBR patients post-ACS. By integrating pharmacodynamic, clinical, and patient-reported outcomes, it will provide information to guide individualized antiplatelet strategies balancing ischemic protection and bleeding mitigation in HBR patients.
CLINICAL TRIAL REGISTRATION UNIQUE IDENTIFIER
NCT05903976, EudraCT 2023-000029-10.
Francesco Costa, Gianpiero Vizzari, S. Zecchino et al.· Cardiovascular Revasculariza...· 0 citations
Evidence suggests that genotype-guided therapy, PFT-guided treatment, and individualized DAPT duration may improve the balance between ischemic protection and bleeding risk in selected high-risk populations, but routine implementation remains limited by inconsistent clinical outcome benefits.
Sai Praneeth Chaparala, Abhishek Hanumanpratap Singh Kshatri, Amritha Suresh et al.· Journal of Basic and Clinica...· 0 citations
AIMS
In patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI), abbreviated dual antiplatelet therapy (DAPT) has been shown to reduce bleeding without increasing ischemic risk. However, the optimal duration in specific subgroups, particularly anemic patients, remains unclear and was the focus of this analysis.
METHODS
This study included 3,364 HBR patients from three prospective trials in the XIENCE Short DAPT Program who underwent PCI with cobalt-chromium everolimus-eluting stents. Anemia was defined as Hb <11 g/dL. The primary endpoint was all-cause death or myocardial infarction; secondary endpoints included BARC 2-5 and 3-5 bleeding. Outcomes by DAPT duration (1 vs 3 months), defined according to study protocol, were assessed using propensity score stratification.
RESULTS
Anemia was present in 514 patients (15.3%). At 1 year, anemic patients experienced higher rates of both ischemic and bleeding events compared with non-anemic patients. Among anemic patients, ischemic outcomes were similar with 1- and 3-month DAPT (15.7% vs 16.3%; adjusted hazard ratio [adjHR] 0.94, 95% confidence interval [CI] 0.59-1.52; p=0.807), whereas 1-month DAPT was associated with a lower incidence of major bleeding (6.1% vs 11.1%; adjHR 0.49, 95% CI 0.24-1.00; p=0.050). In non-anemic patients, ischemic and bleeding outcomes were similar irrespective of DAPT duration.
CONCLUSIONS
Among HBR patients undergoing PCI, abbreviated DAPT was associated with comparable ischemic outcomes regardless of anemia status. In patients with baseline anemia, 1-month DAPT was associated with lower major bleeding without an apparent ischemic trade-off.
F. D. Di Muro, S. Sartori, D. Angiolillo et al.· European Journal of Preventi...· 0 citations
The optimal duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) continues to evolve, but current recommendations derived largely from Western data may not reflect the clinical profile of Indian patients, underscoring the need for region-specific guidance.
To develop consensus-based, India-specific recommendations on DAPT duration in ACS by integrating global evidence with real-world clinical considerations.
A modified Delphi process was conducted among experienced interventional cardiologists across India. Participants reviewed evidence summaries and anonymously rated ten statements on prolonged, shortened, and risk-stratified DAPT strategies. Consensus was defined as ≥75% agreement.
All 34 cardiologists completed the survey (100% response). Consensus (≥≥70%) was achieved for all statements. Strong agreement supported prolonged DAPT in high-thrombotic-risk ACS (97.1%) and balancing ischemic and bleeding risks (94.1%). Agreement with the ESC 6-month DAPT recommendation for stable DES percutaneous coronary intervention (PCI) was lower (61.8%), reflecting preference for extended therapy in Indian practice. While short DAPT reduced bleeding (85.3%), most experts acknowledged higher MI risk in ACS, consistent with SMART-DATE and STOPDAPT-2 ACS (79.4%). Prolonged DAPT (≥≥12 months) in complex PCI received strong support (97%), with universal agreement that it reduces MACE and cardiothrombotic events (100%). Key factors favoring extended therapy included smoking and prior MI/stent thrombosis (97% each), as well as procedural complexity. Routine PPI cotherapy was endorsed by 79.4%.
The GOLD-DAPT consensus offers practical, risk-adapted recommendations for Indian ACS patients, supporting individualized rather than fixed-duration DAPT and emphasizing the need for India-specific prospective data to guide future national policy.
Nagaraj Desai, G. Shetty, Naveen Chandra et al.· Heart India· 0 citations
Background.
Optimizing the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) remains challenging, especially in patients with high bleeding risk and diabetes mellitus, where stent thrombosis risk is significantly increased due to delayed endothelialization.
Objective.
To demonstrate the safety of early DAPT discontinuation based on individual assessment of stent endothelialization using optical coherence tomography (OCT).
Materials and Methods.
We present a clinical case of a 71-year-old female with type II diabetes, atrial fibrillation (CHA2DS2-VASc score of 6), functional class II exertional angina, and a history of left anterior descending (LAD) artery stenting. Risk stratification indicated a high hemorrhagic status: HAS-BLED score of 3, PRECISE-DAPT score of 17, ARC-HBR score of 2, and a CRUSADE score of 49 (corresponding to an 11.9 % risk of major bleeding). Baseline OCT revealed significant narrowing: the minimal lumen area in the LAD was 3.51 mm² (56 % area stenosis), and 2.08 mm² in the right coronary artery (RCA) (72 % area stenosis). Stenting of LAD and right coronary artery was performed using amphilimus-eluting polymer-free stents. DAPT discontinuation was planned at 1 month contingent on sufficient endothelialization per control OCT.
Results.
Follow-up OCT at one month demonstrated neointimal coverage of 81.18 % of the struts in the LAD and 95.9 % in the RCA. No evidence of stent thrombosis or restenosis was observed. The patient was transitioned to clopidogrel monotherapy, alongside ongoing anticoagulant therapy for the prevention of thrombotic complications associated with atrial fibrillation. During the one-year follow-up period, no ischemic or hemorrhagic adverse events were registered, and there was no recurrence of angina symptoms.
Conclusion.
The application of OCT for the evaluation of stent strut endothelialization provides a robust rationale for shortening DAPT duration to 1 month in patients with high hemorrhagic risk. This strategy minimizes bleeding threats without escalating the incidence of ischemic events, even in the presence of concomitant diabetes mellitus and multiple comorbidities.
A. Prokhorikhin, Yu. V. Kukushkina, D. D. Zubarev et al.· Translational Medicine· 0 citations
