The antithrombotic management of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) poses numerous challenges. Triple antithrombotic therapy (TAT), which combines dual antiplatelet therapy (DAPT) with oral anticoagulation (OAC), provides anti-ischemic protection but increases the risk of bleeding. Therefore, TAT is generally limited to a short phase (1 week) after PCI, followed by aspirin withdrawal and continuation of 6–12 months of dual antithrombotic therapy (DAT), comprising OAC plus clopidogrel, followed by OAC alone. This pharmacological approach has been shown to mitigate bleeding risk while preserving adequate anti-ischemic efficacy. However, the decision-making process remains complex in elderly patients and those with co-morbidities, significantly influencing ischemic and bleeding risk. In this review, we discuss the available evidence in this area from randomized clinical trials and meta-analyses for post-procedural antithrombotic therapies in patients with non-valvular AF undergoing PCI.

Dual antiplatelet therapy (DAPT) is the gold standard for the antithrombotic management of patients with an acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Implementation of intensified or prolonged DAPT regimens has proven to lower the risk of ischemic events but at the expense of increased bleeding. Importantly, bleeding is a predictor of poor prognosis. Risk stratification and selection of tailored antiplatelet strategies to maximize the net clinical benefit in individual patients with ACS or undergoing PCI is therefore potentially beneficial. Recently, novel approaches including DAPT de-escalation or escalation have been proposed as possible alternatives to standard DAPT. These strategies, which are generally based on patient’s risk profile, genetics, and/or platelet function have been proposed to offer more tailored treatments in patients with ACS or PCI, with the ultimate goal of providing adequate ischemic protection while mitigating the risk of bleeding. This review summarizes the available evidence on DAPT de-escalation or escalation (both guided and unguided) and discusses the practical implications of these strategies in the contemporary management of patients with ACS and/or undergoing PCI.

Recent evidence suggests that visit-to-visit low-density lipoprotein cholesterol (LDL-C) variability-a measure of intraindividual lipid fluctuation over time-may independently influence cardiovascular risk. This study evaluated the impact of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and inclisiran on LDL-C variability compared to standard lipid-lowering therapy (LLT) in a real-world population of very high-risk patients. We conducted a longitudinal, observational study including 618 patients at very high cardiovascular risk, treated at a single tertiary center. Patients were stratified into 3 groups: standard LLT (statins ± ezetimibe), PCSK9i, or inclisiran. LDL-C variability was assessed at 4 follow-up time points using both SD and coefficient of variation (CV), excluding the first lipid measurement to minimize early response bias. High variability was defined as SD or CV above the population median. Major adverse cardiovascular events (MACE) were collected as exploratory outcomes. Patients receiving PCSK9i or inclisiran had significantly lower LDL-C variability compared to those on standard LLT (mean SD: 8.2 and 8.5 vs. 20.5 mg/dL; P < .001; mean CV: 0.17 and 0.16 vs. 0.31; P < .001). High variability in both SD and CV was observed in 77.3% of patients on standard LLT, but only in 17.2% and 17.1% of patients on PCSK9i and inclisiran, respectively. MACE incidence was higher in patients with high variability (12.5% vs. 6.1%, P = .012). Multivariate analysis confirmed that treatment with PCSK9i or inclisiran was independently associated with lower LDL-C variability. In patients at very high cardiovascular risk, PCSK9i and inclisiran therapies are associated with significantly lower visit-to-visit LDL-C variability compared to standard statin-based regimens. These findings support the importance of not only achieving LDL-C targets but also maintaining lipid stability over time, which may contribute to improved cardiovascular outcomes.

The optimal long-term antithrombotic treatment of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) remains controversial. Current guidelines recommend a short initial period of triple antithrombotic therapy (e.g., 1 week), followed by dual therapy consisting of an oral anticoagulation agent and a single antiplatelet agent for 6 months in patients undergoing elective PCI and 12 months in patients with acute coronary syndromes. After this course of combination therapy, anticoagulation monotherapy is recommended. In daily practice, however, the optimal strategy for long-term antithrombotic therapy remains debated. A growing body of evidence supports the safety and efficacy of oral anticoagulation monotherapy, but its use in clinical practice remains inconsistent. This review aims to evaluate the available evidence on chronic antithrombotic regimens in patients with AF undergoing PCI, with a focus on key clinical considerations, such as the selection of optimal long-term therapy that balances ischemic and bleeding risks. It also highlights that, despite robust supporting evidence, significant gaps persist in real-world implementation.