Search Results (439)

The left atrial appendage is well recognized as the site of thrombus formation in patients with atrial fibrillation. However, in patients who are either unsuitable for long-term oral anticoagulation or in whom this therapy is inefficient, left atrial occlusion has emerged as a mechanical strategy option to diminish stroke risk. Minimally invasive percutaneous and standalone surgical thoracoscopic techniques are appearing as viable options for left atrial appendage exclusion, each with distinct procedural risk profiles and characteristics, as well as evidence from trials or registers. We suggest that the choice between percutaneous and thoracoscopic left atrial appendage occlusion should be individualized, ideally within the multidisciplinary heart team, considering left atrial appendage anatomy, patient bleeding and thromboembolic risk profile, comorbidities, prior cardiac interventions, and institutional expertise and resources. We aim to present in this review the value of multimodality imaging in patient selection for minimally invasive left atrial appendage occlusion to minimize the possibility of complications, and to compare technical advancements and indications for percutaneous and standalone thoracoscopic left atrial appendage occlusion. Full article

Background: Percutaneous left atrial appendage occlusion (LAAO) is an established nonpharmacologic strategy for stroke prevention in atrial fibrillation (AF). Its comparative effectiveness and safety relative to contemporary medical therapy, including direct oral anticoagulants (DOACs), remain uncertain following recent large randomized controlled trials (RCTs). Methods: We performed a systematic review and meta-analysis of RCTs comparing catheter-based LAAO with medical therapy in AF patients. PubMed, CENTRAL, and ScienceDirect were searched from inception through May 2026. Dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using random-effects models. The primary outcome was the composite primary endpoint. Secondary outcomes included all-cause death, cardiovascular death, all stroke/TIA, ischemic stroke/TIA, systemic embolism, major bleeding, and nonprocedural major bleeding. Risk of bias was assessed using ROB 2. Results: Six RCTs were included, contributing 7073 participants (3729 LAAO; 3344 medical therapy). LAAO was not associated with significant differences in the composite endpoint (RR 1.02; 95% CI 0.85–1.23), all-cause death (RR 1.02; 95% CI 0.79–1.31), cardiovascular death (RR 0.93; 95% CI 0.67–1.29), all stroke/TIA (RR 1.06; 95% CI 0.81–1.38), ischemic stroke/TIA (RR 1.24; 95% CI 0.88–1.76), systemic embolism (RR 0.76; 95% CI 0.12–4.77), or total major bleeding (RR 0.93; 95% CI 0.77–1.13). LAAO significantly reduced nonprocedural bleeding (RR 0.54; 95% CI 0.46–0.63; p < 0.0001; I² = 0.0%). Heterogeneity was low to moderate across outcomes. Conclusions: No significant differences were observed between LAAO and medical therapy for the composite endpoint, mortality, or thromboembolic outcomes; however, confidence intervals for ischemic stroke/TIA and systemic embolism remained wide and cannot exclude a clinically meaningful excess of thromboembolic events after LAAO. LAAO was associated with a substantial and consistent reduction in nonprocedural bleeding. These findings suggest LAAO may be considered an individualized alternative to oral anticoagulation for selected patients with high bleeding risk or anticoagulation intolerance, weighing upfront procedural risk against this bleeding benefit, while uncertainty for rare thromboembolic outcomes remains to be resolved. Full article

Background/Objectives: This study assessed the impact of different postoperative antithrombotic strategies on graft patency and overall survival after open posterior repair of popliteal artery aneurysms (PAAs). Methods: A retrospectively maintained dataset of consecutive PAAs electively treated in 40 centers between January 2010 and December 2023 was analyzed. The study included patients undergoing elective open posterior repair. Primary outcomes were primary patency and overall survival according to postoperative antiplatelet or anticoagulant therapy. Secondary outcomes included secondary patency and major adverse cardiovascular events (MACEs). Kaplan–Meier analysis, log-rank testing, and Cox regression models were applied. Results: Overall, 638 patients were included. The cohort was predominantly male (96%), with a median age of 70 years. At 30 days, one death (0.2%) and seven MACEs (1.1%) occurred. Postoperative therapy was not associated with 30-day primary patency or MACEs. At a median follow-up of 30 months, overall survival was 90.3%. Kaplan–Meier analysis showed comparable overall survival across antithrombotic regimens, with a significant difference observed only between patients receiving combined anticoagulant and antiplatelet therapy and those receiving other regimens (p = 0.018). No differences emerged between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs), nor between single or dual antiplatelet therapy and anticoagulation. Multivariable Cox regression showed that combined therapy was associated with poorer overall survival compared with other postoperative antithrombotic regimens (CT vs. others: HR of 1.30). Primary and secondary patency were also similar among regimens except for combined therapy (primary patency: p = 0.004; secondary patency: p = 0.018). Conclusions: Postoperative medical therapy was not associated with 30-day outcomes. During long-term follow-up, overall survival and graft patency were lower in patients receiving combined anticoagulant and antiplatelet therapy. Bleeding outcomes were not captured in this registry; as bleeding may contribute to the worse outcomes observed with combined therapy, this represents an important limitation. Full article

Background/Objectives: As population aging increases the prevalence of atrial fibrillation (AF), the use of direct oral anticoagulants (DOACs) has expanded for thromboembolism prevention. Although DOACs offer advantages over vitamin K antagonists (VKAs), gastrointestinal bleeding (GIB) remains the most common extracranial adverse event. Current guidelines address global bleeding risk but provide limited guidance on site-specific gastrointestinal risk assessment and prevention. This narrative review aims to summarize current evidence on the mechanisms, etiologies, and risk factors for DOAC-associated gastrointestinal bleeding and to propose a pragmatic, risk-based framework to support clinicians in individualized bleeding prevention. Methods: A narrative review of studies published between 2004 and 2025 was conducted, including randomized clinical trials, real-world evidence, meta-analyses, and major society guidelines. Evidence addressing DOAC safety profiles, gastrointestinal bleeding etiologies, patient-level risk factors, medication interactions, and preventive strategies was analyzed. Results: Gastrointestinal bleeding in patients treated with DOAC is strongly influenced by underlying gastrointestinal pathology, comorbid conditions, and concomitant medications. Established risk factors include prior gastrointestinal hemorrhage, Helicobacter pylori infection, gastrointestinal malignancy, diverticulosis, and angiodysplasia, as well as the use of nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelet therapy, or selective serotonin reuptake inhibitors (SSRIs). DOACs differ in gastrointestinal safety: apixaban consistently demonstrates the most favorable profile, whereas rivaroxaban and high-dose dabigatran show higher GIB rates. Preventive strategies such as H. pylori testing and eradication, proton pump inhibitor use in high-risk individuals, avoidance of NSAIDs and unnecessary antiplatelet therapy, and individualized DOAC selection may help reduce bleeding risk. Conclusions: Gastrointestinal bleeding risk in patients receiving DOAC therapy should be assessed using a site-specific and dynamic approach. A structured strategy integrating baseline risk evaluation, correction of modifiable factors, tailored anticoagulant selection, and risk-adapted follow-up may improve the safety of anticoagulation. The proposed framework may provide a pragmatic approach to individualized bleeding risk mitigation while preserving the benefits of DOAC therapy; however, prospective validation is required before its routine implementation can be recommended. Full article

Background: Venous thromboembolism (VTE) remains a clinically relevant complication following major orthopaedic procedures, particularly total hip arthroplasty (THA), total knee arthroplasty (TKA), and fracture surgery. Although low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs) are widely regarded as standard pharmacological options, aspirin (acetylsalicylic acid, ASA) has gained renewed attention because of its low cost, oral administration, and favourable bleeding profile. However, the available evidence is heterogeneous, and its interpretation is complicated by differences in patient selection, timing and duration of prophylaxis, diagnostic methodology, aspirin dosing regimens, and the increasing adoption of modern fast-track arthroplasty pathways. Methods: A structured evidence-based review was conducted in accordance with PRISMA 2020 principles. PubMed, Embase, Web of Science, and the Cochrane Library were searched through September 2025 for randomised controlled trials (RCTs), major international clinical practice guidelines, and selected high-level studies relevant to the interpretation of aspirin-based orthopaedic thromboprophylaxis. Nine RCTs, four major guideline documents, and sixteen additional Level I–II studies were included. Outcomes of interest were symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, and mortality. Risk of bias was assessed using the Cochrane ROB 2 framework. Owing to marked methodological heterogeneity, no formal pooled meta-analysis was undertaken. Results: The available RCT evidence suggests that aspirin may perform adequately within structured sequential or risk-stratified prophylaxis strategies, but not in all clinical settings. In arthroplasty, EPCAT II demonstrated non-inferiority of aspirin when introduced after an initial five-day course of rivaroxaban, whereas CRISTAL showed higher early symptomatic VTE rates when aspirin was used as sole primary prophylaxis from postoperative day 0. Importantly, thromboembolic events in CRISTAL occurred earlier in the aspirin cohort, supporting the concept that anticoagulant therapy remains important during the immediate postoperative hypercoagulable phase. In trauma surgery, PREVENT CLOT established non-inferiority of aspirin compared with LMWH for 90-day mortality; however, the predominantly young study population and the inclusion of upper-extremity fractures limit extrapolation to elderly hip fracture patients. Several smaller RCTs reported no major differences between aspirin and anticoagulants, but these studies were frequently underpowered and relied on less sensitive diagnostic strategies. Historical and contemporary guidelines remain heterogeneous, and evidence from modern fast-track arthroplasty pathways suggests that current trial-based conclusions may not be directly generalisable to short-duration prophylaxis settings. Conclusions: Aspirin may have a role in orthopaedic thromboprophylaxis when used within structured, risk-adapted or sequential protocols, particularly in standard-risk arthroplasty patients and selected trauma populations. However, current evidence does not support its universal use as sole primary prophylaxis in major orthopaedic surgery, especially during the early postoperative hypercoagulable phase or in high-risk patients. Furthermore, the available literature does not permit definitive recommendations regarding the optimal aspirin dose or duration of prophylaxis. The generalisability of the existing literature is further limited by methodological heterogeneity and by the absence of RCTs directly evaluating ultra-short anticoagulant regimens versus prolonged aspirin prophylaxis in modern fast-track arthroplasty. Further high-quality, standardised trials are required. Full article

Background and Clinical Significance: We report an exceptionally rare case of mechanical aortic valve replacement necessitated by self-inflicted needle penetration with aortic valve and left ventricular involvement in a patient with recurrent self-harm behavior. Case Presentation: A 24-year-old female with post-traumatic stress disorder and emotionally unstable personality disorder, borderline type, presented with dyspnea two weeks after self-inserting multiple needles into her thorax. Computed tomography revealed a needle lodged in the aortic root and an intramyocardial needle with hemorrhagic pericardial effusion. Emergency sternotomy revealed inflammatory destruction of the right coronary aortic cusp with complete perforation. Following failed reconstruction attempts, mechanical aortic valve replacement was performed. The patient survived the immediate postoperative period but demonstrated recurrent non-adherence to oral anticoagulation, including multiple episodes of over- and under-anticoagulation. More than six years after surgery, she presented with cardiogenic shock due to prosthetic valve thrombosis after discontinuing warfarin for two weeks. Despite venoarterial ECMO and fibrinolytic therapy, she died from refractory left ventricular failure. Conclusions: This case highlights critical challenges in managing patients with severe psychiatric disorders requiring mechanical valve prostheses and suggests that bioprosthetic valves may warrant careful consideration in patients with major concerns regarding long-term anticoagulation adherence. Full article

Background: AF in the setting of cardiac amyloidosis is associated with a high risk of TEs, irrespective of CHA2DS2-VASc score. While warfarin has been the traditional anticoagulant, DOACs offer a promising alternative, but their safety in this population remains underexplored. This study aimed to evaluate the prevalence of thromboembolic events (TEs), including stroke and transient ischemic attack (TIA), and major bleeding events in patients with cardiac amyloidosis (CA) and atrial fibrillation (AF) treated with either warfarin or direct oral anticoagulants (DOACs). Additionally, we aimed to explore whether DOACs are at least as effective as warfarin in protecting against TEs in this population. Methods: This retrospective cohort study analyzed 422 patients with confirmed CA and AF from Mayo Clinic, with a median follow-up of 4.3 years. Data on anticoagulation therapy, baseline characteristics, and outcomes (TEs and bleeding) were collected. Statistical analyses included chi-square tests, t-tests, and Cox regression to assess the relationship between anticoagulation and TE. Results: Among 422 patients, 21 experienced a TE. The annual event rate was 0.83% for warfarin and 0.67% for DOACs, with no significant difference (HR 0.66, CI 0.22–2.01, p = 0.5). Patients with anticoagulation interruptions > 5 days had increased TE risk (HR 3.19, CI 0.97–10.5, p = 0.056). The bleeding rate was 9.9% over 4.3 years (2.33% per year), with no significant differences between anticoagulants. Conclusions: Both warfarin and DOACs have similar, low risks of TEs in CA and AF patients. However, anticoagulation interruptions were associated with increased TE risk, emphasizing the challenges in managing anticoagulation in this population. Full article

Background/Objectives: Atrial fibrillation (AF) is the most common supraventricular arrhythmia and one of the most commonly encountered heart conditions in clinical practice. Emerging evidence suggests a significant role of inflammation, endothelial disfunction and extracellular matrix (ECM) remodeling in the pathogenesis of AF. Population studies have also suggested an association between AF and cerebral small vessel disease (CSVD), with growing evidence indicating that the burden of certain markers of CSVD is greater in women. However, the association between female sex and CSVD remains poorly understood. The aim of this study was thus to investigate the role of female sex in the association between circulating biomarkers and the presence of CSVD in AF patients undergoing oral anticoagulant therapy. Methods: The Strat-AF study is an observational, prospective, single-center, hospital-based study enrolling elderly patients with AF. Results refer to 170 patients (59 women and 111 men). Recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging (MRI) and circulating biomarker assessments. Results: From a multivariate logistic regression analysis adjusted for multiple confounders, independent predictors were: in women, elevated vWF levels for the presence of lacunar infarcts [OR 3.24 (1.23–8.55), p = 0.018], elevated MMP-12, TIMP-1, TIMP-2, and TIMP-4 levels for the presence of CMBs [OR 7.76 (1.60–37.69), p = 0.021; OR 1.90 (1.02–3.52), p = 0.042; OR 2.46 (1.27–4.80), p = 0.008; and OR 2.36 (1.12–4.95), p = 0.023, respectively], elevated IL-6 and MMP-2 levels for the presence of WMH [OR 10.65 (1.31–86.67), p = 0.027; OR 3.36 (1.23–9.15), p = 0.018, respectively] and elevated MMP-12 and TIMP-2 levels for the presence of bgEPVS [OR 2.57 (1.22–5.93), p = 0.027; OR 2.15 (1.03–4.53), p = 0.043, respectively]; and in men: elevated TIMP-1 levels for the presence of WMH [OR 2.10 (1.08–4.08), p = 0.030], elevated TIMP-1 levels for the presence of bgEPVS [OR 2.20 (1.11–4.38), p = 0.025] and elevated TIMP-1 levels for SVDs positivity [OR 7.25 (2.18–24.15), p = 0.001]. Conclusions: These results from the Strat-AF study demonstrated that a complete biohumoral and instrumental assessment can jointly identify female patients with AF at higher risk of CSVD. These findings pave the way for the implementation of clinical protocols incorporating brain MRI and circulating biomarkers as potential innovative tools for an increasingly refined—and sex-specific—stratification of cardiovascular risk in AF patients undergoing oral anticoagulant therapy. Full article

Background: The optimal antiplatelet strategy after transcatheter aortic valve implantation (TAVI) in patients who do not require long-term oral anticoagulation remains debated. Randomized trial evidence supports single antiplatelet therapy (SAPT) over dual antiplatelet therapy (DAPT), yet real-world practice patterns and the magnitude of benefit in contemporary TAVI populations remain heterogeneous. Methods: We analyzed consecutive patients undergoing TAVI at a single tertiary center between April 2009 and April 2023 who were discharged on an antiplatelet regimen only. Patients on chronic oral anticoagulation were excluded. The exposure was defined by the discharge regimen (SAPT vs. DAPT), treated as a time-varying variable with person-time split at the documented date of any regimen change. The pre-specified efficacy endpoint was ischemic major adverse cardiovascular events (iMACE: death, stroke, or myocardial infarction); net adverse clinical events (NACEs) added major bleeding. The primary analysis was a time-varying Cox model adjusted for baseline variables. Sensitivity analyses included an intention-to-treat Cox model, a 6-month landmark Cox model, and an inverse-probability-of-treatment-weighted (IPTW) time-varying Cox model. Results: Of 662 eligible patients, 147 (22.2%) were discharged on SAPT and 515 (77.8%) on DAPT. Median follow-up was 34 months (IQR 14–52). During follow-up, 141 iMACE and 146 NACEs occurred. In the primary time-varying Cox model, the adjusted hazard ratio for DAPT versus SAPT was 1.28 (95% CI 0.81–2.04; p = 0.292) for iMACE and 0.71 (95% CI 0.44–1.14; p = 0.159) for NACE. None of the sensitivity models demonstrated a statistically significant difference between groups. Major bleeding was rare (six events; two SAPT, four DAPT). The 30-day landmark analysis showed no signal of an effect of regimen on late stroke (HR 1.12, 95% CI 0.39–3.12). Conclusions: In a contemporary real-world TAVI cohort, no statistically significant difference between SAPT and DAPT was observed for ischemic or net adverse clinical events. These findings demonstrate no ischemic disadvantage of SAPT compared with DAPT in real-world practice and are consistent with the randomized evidence base supporting SAPT as a reasonable default antiplatelet strategy after TAVI in patients without another antithrombotic indication. The bleeding endpoint was underpowered, and the expected bleeding advantage of SAPT could not be independently evaluated in this cohort. Full article

Over the past two decades, the combined use of long-term anticoagulation and antiplatelet therapy following percutaneous coronary intervention has been extensively investigated. Efforts to define an optimal antithrombotic strategy—balancing protection against thrombotic and thromboembolic events with minimization of bleeding risk—have led to the design and conduct of randomized clinical trials. This narrative review synthesizes the main evidence comparing different antithrombotic approaches in this setting, with particular focus on regimens stratified by oral anticoagulant type and on the direct comparison between aspirin- and clopidogrel-based double antithrombotic therapy, as evaluated in a limited number of recent studies. Further large-scale randomized data comparing these two regimens are needed to strengthen the current evidence and clarify this issue, as well as to evaluate the role of platelet function and/or genetic testing in guiding the selection of the optimal antiplatelet agent. Full article

Background: Left atrial appendage occlusion (LAAO) requires a significant upfront investment, which is in contrast with the more gradual, long-term costs of direct oral anticoagulants (DOACs). Objective: We performed a budget impact analysis exploring the financial impact of increasing the number of LAAO procedures in a high-stroke-risk population over a 10-year time horizon from the perspective of the healthcare providers under the Italian National Healthcare Service. Methods: Two alternative scenarios simulating an increased uptake of the LAAO therapy were compared to the estimated volume of LAAO procedures performed (baseline scenario: 1341 procedures): (1) Alternative Scenario I (3314 procedures) based on the level of penetration observed in the Italian region performing the highest rate of LAAO procedures; (2) Alternative Scenario II (7672 procedures): LAAO therapy uptake set to attain 5% of the estimated target population. Clinical data were extracted from a propensity-matched, multicenter cohort of 554 AF patients at a very high thromboembolic risk profile (CHA₂DS₂-VASc score ≥ 5) treated with LAAO or DOACs. Results: Cumulative cost savings in Alternative Scenario I were around €4.9 million compared to the baseline. When comparing Scenario II to the baseline scenario, savings added up to €15.8 million over 10 years. The break-even point occurred between the seventh and eighth years. Cost savings were observed even in the instance that all DOAC prices would decrease as generics became available. Conclusions: The widespread use of LAAO therapies in a population of AF patients at very high stroke risk may yield substantial long-term benefits, as the initial investment in the LAAO procedure and device would be counterbalanced within 8 years. Full article

Aspirin has been the default backbone of antiplatelet therapy after percutaneous coronary intervention (PCI) for over two decades, anchored by landmark trials that established 12-month dual antiplatelet therapy (DAPT) as the standard of care. Three developments have prompted reassessment of this paradigm: the markedly lower thrombotic risk of contemporary drug-eluting stents, the greater potency and consistency of potent P2Y₁₂ inhibitors (ticagrelor, prasugrel), and increasing recognition that major bleeding independently worsens outcomes after PCI. Recent randomised trials have systematically tested aspirin withdrawal at varying time points. Immediate aspirin-free strategies (NEO-MINDSET, STOPDAPT-3) demonstrated an early signal of excess ischaemic events in the ACS component of enrolled populations, suggesting that aspirin remains important during the earliest post-PCI period in ACS. One-month strategies (T-PASS, ULTIMATE-DAPT, TARGET-FIRST) and three-month strategies (TWILIGHT, TICO, DUAL-ACS) showed that transition to P2Y₁₂ monotherapy after an initial DAPT period significantly reduces bleeding without increasing ischaemic events in selected populations. Beyond one year, long-term randomised trials including the HOST-EXAM 10-year follow-up (Lancet 2026) and the STOPDAPT-2 5-year landmark analysis (Circ Cardiovasc Interv 2026), together with study-level meta-analyses (PANTHER) and recent individual patient data meta-analyses, provide converging evidence that clopidogrel monotherapy outperforms aspirin for chronic secondary prevention without excess bleeding. The choice of P2Y₁₂ agent is critical: clopidogrel monotherapy in ACS during the first post-procedural year carries excess thrombotic risk owing to CYP2C19 pharmacogenomic variability, whereas ticagrelor and prasugrel provide more reliable protection. This review synthesises the mechanistic rationale, trial evidence across all time points, special clinical contexts (oral anticoagulation, coronary artery bypass grafting, high bleeding risk), guideline evolution, and methodological considerations, providing a practical framework for individualising post-PCI antiplatelet therapy. Full article

Purpose: Proton pump inhibitors are commonly used during oral anticoagulant therapy in patients with atrial fibrillation, but evidence regarding outcomes beyond upper gastrointestinal bleeding remains limited. We evaluated whether concomitant proton pump inhibitor use during oral anticoagulant therapy was associated with thromboembolic events, bleeding outcomes, and all-cause mortality. Methods: This retrospective multicenter cohort study included patients with atrial fibrillation who initiated oral anticoagulant therapy. Concomitant proton pump inhibitor use was modeled as a time-varying exposure with a prespecified 7-day lag. The primary outcome was a composite of thromboembolic events, major bleeding, and all-cause mortality. Secondary outcomes included each component outcome and gastrointestinal bleeding. Associations were estimated using time-dependent Cox proportional hazard models after multiple imputation of missing baseline variables. Results: Among 11,203 patients (median age 71 years [interquartile range 62–78]; 4743 women [42.3%]), 7-day lagged time-varying proton pump inhibitor exposure was associated with a higher risk of the composite outcome (hazard ratio 1.29, 95% confidence interval 1.08–1.55), major bleeding (1.80, 1.36–2.37), gastrointestinal bleeding (1.77, 1.18–2.66), and all-cause mortality (1.58, 1.00–2.48). No statistically significant association was observed for thromboembolic events. Across robustness analyses, the overall pattern was broadly maintained, although estimates varied according to exposure timing. Conclusions: In this observational cohort of patients with atrial fibrillation receiving oral anticoagulant therapy, concomitant proton pump inhibitor use modeled with a 7-day lagged time-varying framework was associated with higher risks of several bleeding-related outcomes and all-cause mortality, but not thromboembolism. These findings should be interpreted as associations rather than causal effects. Full article

Direct oral anticoagulants (DOACs) are the standard first treatment for patients with venous thromboembolism. Unfortunately, some patients develop recurrent thromboembolism despite adherence to anticoagulation. This remains a significant clinical challenge with no randomized data to guide therapy. This review summarizes the available evidence for the management of recurrent venous thromboembolism (VTE) and DOAC failure, and we propose our group consensus and management algorithm. Full article

Background: Lower limb arterial calcification (LLAC) is a robust imaging biomarker of peripheral artery disease (PAD) severity. Vitamin K antagonists are presumed to accelerate cardiovascular calcification. Direct oral anticoagulants (DOACs) may influence vascular calcification differently, but lower limb data are limited. Methods: We performed a single-center retrospective cross-sectional study comparing LLAC on clinically acquired non-contrast CT between DOAC users and controls without anticoagulation. Patients were propensity score-matched 1:1 (48 DOAC vs. 48 control; n = 96) using baseline clinical covariates. Associations between LLAC scores and perioperative or cardiovascular events were assessed. Segment-specific LLAC was quantified on non-contrast CT and normalized for arterial segment length. A prespecified exposure–duration sensitivity analysis compared the outcomes in patients with ≥5 years of continuous DOAC therapy (n = 22) versus matched controls. Results: In the matched cohort, total LLAC scores did not differ significantly between DOAC and control groups (infrarenal aorta: median 7596.0 vs. 8637.0 (p = 0.487), iliac segment: median 5689.5 vs. 5193.5 (p = 0.602). However, in patients with ≥5 years of DOAC use, LLAC scores were significantly lower in proximal segments: infrarenal aorta median 5593.5 vs. 11,185.0 (p = 0.001997) and iliac arteries 5624.5 vs. 11,501.0 (p = 0.001867)). Higher LLAC was associated with major adverse cardiovascular events (such as myocardial infarction, stroke, or significant bleeding) in controls (p = 0.0023) but not in DOAC-treated patients. Conclusions: In this propensity-matched, cross-sectional CT study, long-term DOAC exposure was associated with lower proximal LLAC scores in a small duration-defined subgroup, while the primary matched analysis showed no overall difference in total LLAC scores. Because baseline (pre-DOAC) imaging was unavailable and residual confounding/survivor bias is possible, these findings should be considered hypothesis-generating and require prospective validation. The cohort reflected a mixed lower-extremity vascular population rather than exclusively classic chronic atherosclerotic PAD, which may limit biological interpretation and generalizability. Full article