Long-Term Antithrombotic Therapy After Percutaneous Coronary Intervention: Secondary Prevention Beyond One Year.

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.