Duration of dual antiplatelet therapy and risk of stent thrombosis in patients undergoing complex PCI: a meta-analysis

Clinical Research in Cardiology https://doi.org/10.1007/s00392-026-02928-0 ORIGINAL PAPER Duration of dual antiplatelet therapy and risk of stent thrombosis in patients undergoing complex PCI: a meta‑analysis Fiorenzo Simonetti1,2 · Claudia Carassia1 · Hector Alfonso Alvarez Covarrubias1 · Michael Joner1 · Thorsten Kessler1,3 · Tobias Rheude1 · Hendrik Sager1,3 · Felix Voll1 · Moritz von Scheidt1 · Erion Xhepa1,3 · Adnan Kastrati1,3 · Salvatore Cassese1,3 Received: 9 March 2026 / Accepted: 17 April 2026 © The Author(s)2026 Abstract Background Patients undergoing complex percutaneous coronary intervention (PCI) have a higher risk of ischemic events and often receive extended dual antiplatelet therapy (DAPT), particularly to protect against stent thrombosis (ST). The selection of an optimal DAPT strategy in this setting remains challenging given the intrinsic ischemic and bleeding risk. Previous observations have not clearly established the impact of non-standard DAPT duration regimens on ischemic events in complex PCI patients. This study aims to assess the effect of non-standard DAPT duration on ischemic events in this setting. Methods and results We searched for randomized trials comparing DAPT duration regimens in patients undergoing complex PCI. The primary outcome was definite/probable ST. Other outcomes were myocardial infarction (MI), all-cause death, and major bleeding. Seven trials with a total of 46,696 patients undergoing either complex (n = 13,469) or non-complex (n = 33,227) PCI were included in the analysis. In complex PCI patients, the risk of definite/probable ST was not significantly different between the non-standard DAPT and standard DAPT groups (incidence rate ratio (IRR) 1.08; 95% confidence intervals (CI) 0.63–1.82). Consistently, the risk of MI (IRR 0.87; 95% CI 0.70–1.09), all-cause death (IRR 0.85; 95% CI 0.51–1.39), and major bleeding (IRR 0.63; 95% CI 0.33–1.19) did not differ significantly between DAPT strategies. Treatment effect for definite/probable ST by DAPT duration strategy was independent of PCI complexity. Conclusions In patients undergoing complex PCI, we found no significant differences in stent thrombosis, myocardial infarction, all-cause death, and major bleeding between DAPT duration strategies. PROSPERO registration number CRD42024617534. Graphical abstract Dual antiplatelet therapy duration and thrombotic risk in patients undergoing complex PCI. Association between DAPT duration and the incidence of definite or probable ST and MI in patients undergoing complex PCI. Complex PCI was defined according to the trial definitions, no restrictions were applied. Standard DAPT was defined as the conventional, non-tailored regimen with a fixed duration of 6 or 12 months. Non-standard DAPT was defined as regimens with modified duration, including extended, abbreviated, or de-escalated approaches. No significant difference in definite/probable ST and MI between complex PCI patients treated with non-standard DAPT and those treated with standard DAPT were detected. DAPT dual antiplatelet therapy, PCI percutaneous coronary intervention, RCTrandomized controlled trial, ST stent thrombosis. * Salvatore Cassese 1 Klinik Für Herz- und Kreislauferkrankungen, TUM Klinikum Deutsches Herzzentrum, Technische Universität München, Munich 80636, Germany 2 Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy 3 DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany Vol.:(0123456789) Clinical Research in Cardiology Keywords Dual antiplatelet therapy · Complex percutaneous coronary intervention · Stent thrombosis · Coronary artery disease Introduction Percutaneous coronary intervention (PCI) is a wellestablished treatment for coronary artery disease (CAD) and currently represents the most frequently performed revascularization strategy [1]. Advances in PCI technology over the years, coupled with the aging population and increased prevalence of comorbidity in patients with CAD, have contributed to a growing proportion of PCI procedures being performed in anatomically complex settings [2, 3]. Complex PCI is associated with an elevated risk of ischemic events and is frequently accompanied by extended dual antiplatelet therapy (DAPT), particularly in order to reduce the risk of stent thrombosis (ST) [4, 5]. ST is an infrequent but serious ischemic complication of PCI procedures. Although rare, it is associated with severe clinical consequences, leading to death in about one in four patients and myocardial infarction (MI) in almost all cases, with a high risk of recurrence [6]. DAPT with aspirin and a P2Y12 inhibitor is a cornerstone after PCI to reduce the risk of thrombotic events, including ST [7–10]. In this context, the use of extended DAPT is considered a valid tool to reduce residual ischemic risk in complex PCI patients [8–11]. However, since complex PCI patients have an increased risk of bleeding regardless of DAPT regimen, the selection of an appropriate DAPT strategy in this setting remains particularly challenging [12, 13]. Current guidelines recommend discontinuing DAPT 1 to 3 months after PCI in patients at high hemorrhagic risk but not at high ischemic risk, prescribing 6 to 12 months DAPT with aspirin and a P2Y12 inhibitor as the standard regimen for patients undergoing PCI without an indication for oral anticoagulation, and considering prolonged DAPT in patients at high ischemic risk, including those undergoing complex PCI [14]. Hence, it is easy to understand as in real-world clinical practice, variations of DAPT durations regimens are common, due to both patient- and physician-related factors [15]. For example, physicians may still be reluctant to shorten DAPT duration in complex PCI patients and tend to extend DAPT duration in this setting, even in HBR patients, mainly because of concerns about ST [16]. Alternative DAPT duration regimens have been tested in patients undergoing complex PCI. However, to date there is no definitive evidence to assess the risk of thrombotic events in patients undergoing non-standard DAPT duration after complex PCI. With this in mind, we designed a meta-analysis to assess whether the duration of DAPT has an impact on the risk of ischemic events in patients undergoing complex PCI. Clinical Research in Cardiology Methods Search strategy and outcome selection The study is registered in PROSPERO (CRD42024617534). Eligible studies enrolled patients who underwent PCI and were randomly assigned to treatment with a non-standard or standard DAPT regimen. Standard DAPT was defined as the conventional, non-tailored regimen with a fixed duration of 6 or 12 months. Non-standard DAPT was defined as regimens with modified duration, including extended or abbreviated approaches. To be eligible, studies were required to report the association between DAPT regimens and outcomes of interest in complex PCI patients. No restrictions (...truncated)