Key result
P2Y12 inhibitor monotherapy or DPI may beat lifelong aspirin beyond one year post-PCI.
Why the study?
Beyond 12 months after PCI, risk shifts toward progressive systemic atherosclerosis rather than stent-related thrombosis, necessitating an updated synthesis of long-term antithrombotic strategies.
Do alternative antithrombotic strategies (P2Y12 inhibitor monotherapy, prolonged DAPT, or dual-pathway inhibition) improve ischemic and bleeding outcomes compared to lifelong aspirin in patients beyond one year post-PCI?
Do alternative antithrombotic strategies (P2Y12 inhibitor monotherapy, prolonged DAPT, or dual-pathway inhibition) improve ischemic and bleeding outcomes compared to lifelong aspirin in patients beyond one year post-PCI?
This review highlights a paradigm shift in long-term post-PCI care, suggesting that individualized strategies like P2Y12 inhibitor monotherapy or dual-pathway inhibition may be superior to the traditional default of lifelong aspirin.
Emphasizes systemic atherosclerosis management beyond 12 months post-PCI; leaves open optimal long-term antithrombotic strategies.
The early period following percutaneous coronary intervention (PCI), particularly the first days to weeks after stent implantation, is characterized by heightened device-related thrombotic risk, and dual antiplatelet therapy (DAPT) during this phase is well established. With contemporary drug-eluting stents (DES) and abbreviated DAPT strategies, late stent-related events have become less frequent, and long-term risk increasingly reflects underlying systemic atherosclerotic disease. Beyond 12 months, the risk profile shifts further: late events increasingly reflect progressive atherosclerosis and systemic vascular disease rather than stent-related thrombosis. This review synthesizes contemporary evidence on long-term antiplatelet and antithrombotic therapy after PCI, with a focus on the period beyond one year. We evaluate the data supporting for lifelong aspirin as the traditional default strategy, as well as the emerging evidence that P2Y12 inhibitor monotherapy may be superior to aspirin in selected post-PCI populations (HOST-EXAM, HOST-EXAM Extended, PANTHER, SMART-CHOICE 3). This review also examines the role of prolonged DAPT in selected high-risk patients (DAPT Trial, PEGASUS–Thrombolysis in Myocardial Infarction (TIMI) 54) and the paradigm of dual-pathway inhibition with low-dose rivaroxaban plus aspirin (COMPASS, VOYAGER-peripheral artery disease (PAD)). In addition, the review considers protease-activated receptor (PAR) antagonism (TRA 2°P–TIMI 50) and precision-based strategies, including CYP2C19 genotype-guided therapy. Special populations, such as patients with diabetes, chronic kidney disease (CKD), polyvascular disease, and those requiring concomitant oral anticoagulation, present distinct long-term management challenges. Thus, novel targets, including factor XIa inhibitors and PAR-4 antagonists, may further refine the antithrombotic approach. Overall, the optimal long-term strategy after PCI is increasingly defined not by fixed timelines but by the dynamic balance between ischemic and bleeding risk.
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Abdelgader et al. (2026) conducted a review in Percutaneous coronary intervention. Long-term antithrombotic therapy (e.g., P2Y12 inhibitor monotherapy, dual pathway inhibition) vs. Lifelong aspirin was evaluated. Beyond one year after percutaneous coronary intervention, individualized strategies such as P2Y12 inhibitor monotherapy or dual pathway inhibition may offer better protection than lifelong aspirin.
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