Antiplatelet Therapy in Chronic Coronary Artery Disease Patients With a History of Angioplasty. When is Aspirin Not Enough? A Systematic Review

Abstract

Background: Antiplatelet therapy represents a cornerstone of secondary prevention in patients with chronic coronary syndrome (CCS) who have undergone percutaneous coronary intervention (PCI). However, the optimal antiplatelet regimen and optimal duration remain under investigation, as treatment must be individualized to balance the thrombotic and bleeding risks. Thus, this systematic review aimed to present the most recent evidence on antiplatelet strategies in chronic coronary syndrome patients with prior PCI, highlighting findings relevant to subgroups with increased thrombotic risk. Methods: A systematic search of the PubMed database, the Cochrane Library, and ClinicalTrials.gov was conducted up to 29 May 2025. Studies were screened and selected based on predefined eligibility criteria. A total of 14 studies were included and were synthesized narratively. Results: Extended dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin, compared to aspirin alone, improved primary outcomes in 5101 patients with stable coronary disease and diabetes mellitus (hazard ratio (HR) 0.81; 95% confidence interval (CI), 0.71–0.93; p = 0.003), and reduced major adverse cardiovascular events (HR 0.85; 95% CI, 0.75–0.96; p = 0.009) among 11,260 patients with history of prior myocardial infarction and additional risk factors such as multivessel coronary artery disease or chronic kidney disease. In 2431 patients, long-term clopidogrel monotherapy, compared to aspirin monotherapy, was associated with improved primary outcomes (HR 0.74; 95% CI 0.63–0.86; p < 0.001) along with a reduction in major bleeding (HR 0.65; 95% CI 0.47–0.90; p = 0.008). Long-term ticagrelor monotherapy, compared to aspirin, was associated with fewer ischemic events, as defined by the primary endpoint (HR 0.73; 95% CI 0.57–0.94; p = 0.014), but an increased risk of Bleeding Academic Research Consortium (BARC) type 2,3, or 5 bleeding (HR 1.52; 95% CI 1.11–2.08; p = 0.009). Subgroup analyses suggested benefits of extended DAPT versus aspirin in patients with peripheral artery disease (n = 246; HR 0.54; 95% CI 0.31–0.95; p = 0.03), in those with two or more implanted stents (n = 505; p = 0.02), and in patients treated for in-stent restenosis (n = 224; p = 0.034). Conclusion: Extended DAPT demonstrated benefits over 30 months, while clopidogrel monotherapy has shown sustained effectiveness for up to 5.8 years in CCS patients with a history of PCI. Individualized treatment based on thrombotic and bleeding risk remains essential. Largescale randomized trials are warranted to define the populations most likely to benefit from long-term intensified antiplatelet therapy. The PROSPERO Registration: CRD420251069004, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251069004.