BACKGROUND:Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive biliary tract cancer with a poor prognosis and a complex tumour microenvironment (TME) that remains poorly understood. OBJECTIVE:This study aimed to investigate the phenotypic and molecular characteristics of B lymphocytes, their interactions with the TME and their prognostic implications. DESIGN:B-cell compartments in the tumour, peritumour, and peripheral blood of iCCA patients were analysed using multimodal single-cell technologies. The B-cell interactome with the iCCA TME was explored in silico, and ex vivo assays assessed the impact of interactions with cancer-associated fibroblasts (CAFs) and tumour cells on B-cell biology. B-cell modulation during chemoimmunotherapy in advanced iCCA was also evaluated. RESULTS:B cells were enriched in adjacent tumour-free tissues and formed mature tertiary lymphoid structures (TLS), correlating with better prognosis. Conversely, tumour-infiltrating B cells were scarce, immature and displayed reduced effector function with increased immunosuppressive features. Coculture with tumour cells or CAFs impaired B-cell differentiation and function, including downregulation of BAFFR in peripheral B cells. IL-6 and TGF-β emerged as major drivers of B-cell dysfunction; dual blockade restored B-cell activation and differentiation. Elevated frequencies of circulating BAFFR+ B cells and hyperexpanded clonotypes were linked to improved chemoimmunotherapy response. CONCLUSIONS:iCCA is characterised by a profoundly immunosuppressive TME that impairs B-cell function through soluble factors and cellular interactions. Our findings identify B cells as biomarkers and therapeutic targets, supporting strategies to restore B-cell function and promote mature TLS to enhance immunotherapy responsiveness in iCCA.

4134 Background: Obesity is an established risk factor for cancer, yet paradoxically may be associated with improved responses to immune checkpoint inhibitors (ICIs). We investigated whether obesity defines a clinically and biologically distinct cholangiocarcinoma (CCA) subtype when treated with ICIs. Methods: Retrospective analysis of Body Mass Index (BMI)-stratified patients (pts) with CCA treated at a single US center (US cohort) and enrolled in a prospective multicenter Italian registry (Italian cohort). High BMI was defined per CDC criteria (overweight 25.0-29.9; obesity ≥30 kg/m²), with cohort-specific cutoffs for analysis (US ≥30; Italy ≥25). Tumor microenvironment (TME) was profiled with bulk RNA-seq and CODEX multiplex imaging and body composition radiomics with TotalSegmentator tool in the US cohort. Chi-square, Pearson correlation or Wilcoxon tests were used to test associations with BMI; overall survival (OS) was assessed with Kaplan-Meier and Cox models. Results: 989 pts were included (661 US; 328 Italy). In the US and Italian cohorts, median age was 62 and 65 years, 51% and 47% were female, and 28% and 43% were obese and overweight, respectively. Metabolic comorbidities included diabetes (US: 15%; Italy: 19%), hypertension (US: 48%; Italy: 45%), and hyperlipidemia (US: 32%; Italy: 15%). Higher subcutaneous-to-visceral fat ratio was associated with improved OS with chemotherapy-ICI (HR 0.89; 95% CI 0.79-0.99; p = 0.036). In both cohorts, patients with high BMI treated with chemotherapy-ICI had significantly longer OS compared with lower-BMI patients (US: 31.6 vs 19.2 months, p = 0.005; Italy: 21 vs 12 months, p = 0.025). In multivariable models (US cohort) both obesity (HR 0.35; 95% CI 0.23-0.52, p < 0.0001) and higher visceral-to-subcutaneous fat ratio (HR 1.79; 95% CI 1.04-3.07, p = 0.037) were independently associated with OS. Combined genomic profiling (n = 906) showed a lower prevalence of KRAS alterations in high-BMI pts (OR 0.56, p = 0.006). RNA-seq (n = 86; obese = 37, non-obese = 49) demonstrated enrichment of fibroblast-associated signatures ( αSMA, PDPN, collagen IV, vimentin ), upregulation of immune checkpoints ( PD-1, PD-L1, TIGIT, LAG-3, VISTA ), and higher GATA3 and IFN-γ expression in obese pts (both p < 0.05). Multiplex CODEX analysis (n = 38; obese = 17, non-obese = 21) revealed an increased co-expression between GATA3 , a regulator of T-cell dysfunction, and granzyme B , a cytotoxic T-cell marker (Pearson ρ = 0.24, p < 0.05), indicating increased abundance of GATA3 ⁺granzyme B⁺ cells in obese pts. Conclusions: In CCA, obesity characterized by predominant subcutaneous adiposity is linked to improved outcomes with ICIs and to a biologically distinct TME enriched in dysfunctional cytotoxic T-cells that may be reinvigorated by checkpoint inhibition. BMI may represent a pragmatic biomarker warranting prospective validation.

507 Background: Cholangiocarcinoma (CCA), categorized as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA), is often diagnosed at an advanced or metastatic stage. Approximately, 10-15% of iCCA harbor mutations in isocitrate dehydrogenase 1 ( IDH1 ) gene. However, data on real-world clinical outcomes and treatment patterns remain scarce. This study aims to provide a better understanding of the management of patients (pts) with m IDH1 CCA. Methods: This retrospective study utilized Citizen Health data, a real-world dataset harmonized across 3000 healthcare institutions, to evaluate United States CCA pts’ basic characteristics, molecular testing data, and treatment patterns. Pts were followed from the date of initial pathologic diagnosis until death or censored at the last activity in the database. In addition to the descriptive analysis, time-to-event endpoints were estimated using Kaplan-Meier (KM). Results: 602 pts diagnosed with CCA from 2007 to 2025 were included; 59.8% were female, median (range) age was 59.5 (22.3-85.8) years; 157 pts (26.1%) had ECOG performance Status 0 and 236 pts (39.2%) of 1. Most pts had iCCA (61.0%) and advanced or metastatic disease (59.8%) at diagnosis. The majority of pts (n=499, 82.9%) underwent biomarker testing. For 395 pts (79.2%), the testing was tissue-based and, for 106 pts (21.2%), it was performed on liquid biopsy. The main method used was next-generation sequencing (NGS) for 275 pts (55.1%) and immunohistochemistry (IHC) for 194 pts (38.9%). Among pts evaluated for IDH1 alterations, 88 pts (18.6%) had m IDH1 CCA with 60 pts (68.2%) diagnosed with advanced/metastatic disease. 80 pts (90.9%) received first-line (1L) systemic therapy for any stage, including gemcitabine-cisplatin (GemCis) (n=26, 32.5%) or GemCis-durvalumab (n=21, 26.3%) and GemCis-nab-paclitaxel (n=12, 15.0%). In the 1L, median (m) PFS was 8.0 months (mo), mOS was 30.0 mo, and disease control rate (DCR) was 84%. 63 pts (71.6%) received second-line (2L) therapy, including ivosidenib monotherapy (n=22; 34.9%) or in combination (n=7, 11.1%). In the 2L, in pts who received ivo-containing regimens (n=29), mPFS was 6.1 mo, mOS was 25.1 mo, and DCR was 69%; while in pts who received other regimens (n=34), mPFS was 4.1 mo, mOS was 20.1 mo, and DCR was 56%. Conclusions: Most pts with CCA were diagnosed with advanced or metastatic disease and the majority of pts had access to biomarker testing. Pts with m IDH1 CCA received mainly GemCis or GemCis-durvalumab as 1L therapy and ivosidenib as 2L therapy as recommended by current guidelines. mOS was longer than expected in each line of treatment, potentially due to survivorship bias, self-selection bias, and a limited number of pts harboring IDH1 mutations. This real-world study corroborates the efficacy finding from ClarIDHy and supports ivosidenib as a valuable 2L treatment option for patients with m IDH1 CCA.

HCC is characterized by a highly vascularized tumor microenvironment (TME), with VETC being a distinctive, frequent and prognostically unfavourable type of this vascular TME. VETC+ HCCs show lymphocyte deprivation and enrichment with large, foamy macrophages distributed close to endothelial cells. This study aimed to characterize these macrophages with a spatial transcriptomic approach. We demonstrated that they exhibit a pro-tumor, M2-like tumor-associated macrophages (TAMs) signature (SPP1, ACP5, GPNMB, and FABP5), distinct from those in VETC- cases. They are enriched with specific pathways involved in immunosuppression and angiogenesis. SPP1, ADAM9 and MMP9 were among the genes mostly upregulated. Immunohistochemistry analysis confirmed strong SPP1 expression in TAMs spatially associated with endothelial cells in VETC+ cases. Our findings suggest that M2-like TAMs in VETC+ HCCs contribute to both angiogenesis and immunosuppression. SPP1 and ADAM9 could represent novel therapeutic strategies to reshape TAMs and suppress VETC onset.

Introduction: Given the complexity of managing unresectable hepatocellular carcinoma (HCC), few Italian centres have implemented integrated multidisciplinary clinics (MDTc), where hepatologists and oncologists jointly assess patients. This study aimed to evaluate whether this model improves survival outcomes in patients treated with atezolizumab and bevacizumab (A+B). Methods: In this multicentre retrospective study, 146 patients with cirrhosis and unresectable HCC treated with A+B were included. Based on the outpatient care model, centres were categorized into two groups: those with MDTc and those with standard oncology clinics, where hepatologists were consulted on demand. Primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes included disease control rate (DCR) and objective response rate (ORR). An inverse probability weighting (IPW) analysis was performed to adjust for baseline imbalances between groups. Results: Seventy-seven (53%) patients were managed in MDTc settings, and 69 (47%) in oncology clinics. Median treatment duration was 6.0 months (IQR 2.0-11.0). Median OS did not significantly differ between groups [19.7 months (95% confidence intervals [CI]: 16.6-23.1) vs. 13.4 months (95% CI: 10.7-19.5); p = 0.07], whereas median PFS was significantly longer in the MDTc group (13.6 months [95% CI: 8.9-NA] vs. 7.7 months [95% CI: 4.9-13.0]; p = 0.02). While ORR was similar, DCR was higher in the MDTc group (70.1% vs. 60.3%; p = 0.05). Patients followed in MDTc remained on first-line therapy significantly longer (8 months [IQR 3-12] vs. 4 months [IQR 1-8]; p = 0.009). Although the overall treatment discontinuation rate did not differ between the two groups, liver-related events were more frequent and accounted for a greater proportion of discontinuations in oncology clinics (40.6% vs. 10.4%; p = 0.04). Furthermore, treatment duration was shorter in patients discontinuing A+B due to liver-related events than other causes (2.5 months [IQR 1.8-6.3] vs. 7.1 months [IQR 3.9-11.2]; p < 0.001). However, in the IPW analysis, the association between MDTc management and clinical outcomes was no longer significant. Conclusions: In patients with unresectable HCC treated with A+B, MDTc management did not significantly improved OS but was associated with better PFS and DCR. These benefits were likely driven by longer treatment duration and lower rates of liver-related decompensation, underscoring the value of integrated hepatologic-oncologic management in this complex population.

Many real-world patients with advanced biliary tract cancer (BTC) are excluded by TOPAZ-1 criteria; this study assessed cisplatin and gemcitabine plus durvalumab (CGD) efficacy and safety in these patients. Data from 1358 patients with advanced BTC treated with first-line CGD across 55 international centers were retrospectively analyzed. Patients were classified as TOPAZ-1-in (meeting all inclusion criteria) or TOPAZ-1-out (meeting ≥ 1 exclusion criterion). Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Furthermore, OS and PFS of the TOPAZ-1-out cohort were compared with reconstructed survival data from the phase III trial. 912 (67.1%) patients were classified as TOPAZ-1-in, and 446 (32.9%) as TOPAZ-1-out. After a median follow-up of 14.5 months (95% CI: 13.7-36.5), OS was 16.1 months in TOPAZ-1-in and 12.5 months in TOPAZ-1-out (HR 0.69, 95% CI: 14.6-16.5, p = 0.0001); PFS was 8.2 versus 6.5 months (HR 0.73, 95% CI: 7.1-8.1, p < 0.0001). Median OS in the TOPAZ-1-out cohort (12.5 months) was nearly identical to the phase III trial experimental arm (12.9 months; HR 1.15, p = 0.13); for PFS the HR was 1.12 (95% CI 0.93-1.42; p = 0.09). Among TOPAZ-1-out patients, active infection, elevated bilirubin, and ECOG PS > 1 were linked to poorer OS, while no detrimental impact emerged for ALT/AST abnormalities, corticosteroid use, renal or hematologic parameters, or prior surgery within 6 months, suggesting treatment effectiveness was broadly maintained across clinical subgroups. Furthermore, TOPAZ-1-out patients experienced no significant increase in adverse events compared with the TOPAZ-1-in group. Real-world data suggest CGD may be effective in TOPAZ-1-out patients, with no evident increase in toxicity, supporting the potential expanded use of the regimen in clinical practice.

The management of hepatocellular carcinoma (HCC) has undergone radical change over the past decade. Immunotherapies now dominate the treatment of advanced-stage disease and are increasingly being evaluated in perioperative and intermediate-stage settings. However, in some instances, positive phase III trials have not translated into adoption by guidelines or regulatory agencies, highlighting the need to harmonize and update the current standards for trial design and end points. In response to these challenges, four scientific societies - the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD), the International Liver Cancer Association (ILCA) and the American Society of Clinical Oncology (ASCO) - appointed representatives to develop a consensus recommendations document addressing current unmet needs and future challenges in HCC trial design and end points. Through a modified Delphi process, 102 consensus statements were developed across several distinct domains: surveillance; early-stage, intermediate-stage and advanced-stage disease; transplant-related contexts; regulatory considerations; and emerging topics. The document rigorously defines target populations, stratification factors, control arms and benchmarks for expected clinical benefit. Collectively, this consensus is intended to provide a dynamic, evidence-based, multisociety roadmap for optimizing trial design, accelerating therapeutic development and improving clinically meaningful outcomes in patients with HCC.

PURPOSE Cholangiocarcinoma is a rare cancer associated with poor prognosis. Pemigatinib was the first FGFR1-3 inhibitor approved for second-line therapy and beyond, on the basis of the phase II FIGHT-202 trial. Here, we assess efficacy and safety of first-line pemigatinib. METHODS FIGHT-302 is a phase III, randomized, global trial evaluating pemigatinib as first-line therapy (ClinicalTrials.gov identifier: NCT03656536 ). Adults with advanced cholangiocarcinoma with FGFR2 rearrangement were randomized 1:1 to receive pemigatinib (13.5 mg once daily) or chemotherapy (1,000 mg/m 2 gemcitabine plus 25 mg/m 2 cisplatin once per day on days 1 and 8 of every 3-week cycle for ≤8 cycles) and were stratified by prior receipt of chemotherapy, geographic region, and tumor burden. Pemigatinib crossover was allowed for patients progressing on chemotherapy. The primary end point was progression-free survival (PFS). Secondary efficacy, safety, and exploratory end points were also analyzed. RESULTS Overall, 4,563 patients were prescreened, 196 were screened, and 167 randomly assigned to receive pemigatinib (n = 83) or chemotherapy (n = 84) before early closure of the study because of a change in standard of care. The median PFS was 8.3 months in the pemigatinib group versus 6.8 months in the chemotherapy group (hazard ratio, 0.58 [95% CI, 0.39 to 0.87]; nominal P = .0078); objective response rate was 47% versus 15%, and the median duration of response was 14.2 versus 6.3 months. Median overall survival was similar (24.4 v 25.0 months, respectively). In the crossover group (n = 42, second-line pemigatinib), the median PFS was 8.1 months. Safety was consistent with the known profile of pemigatinib. CONCLUSION To our knowledge, this was the largest, first-line, randomized, phase III trial of a targeted therapy for advanced FGFR2- rearranged cholangiocarcinoma. Pemigatinib demonstrated prolonged median PFS compared with chemotherapy, with no new safety findings.

The management of unresectable and advanced hepatocellular carcinoma (HCC) has been transformed by the introduction of immune checkpoint inhibitor-based combinations, which have improved response and survival and expanded first-line treatment options. The availability of multiple effective regimens has introduced new challenges in therapeutic decision making. In the absence of validated predictive biomarkers or head-to-head comparisons, first-line treatment selection remains largely guided by clinical characteristics, contraindications and anticipated toxicity, while the optimal sequencing of therapy following first-line immunotherapy remains uncertain. Locoregional therapies continue to play an important role in selected patients with liver-confined disease, further broadening the range of therapeutic strategies available in clinical practice. In Europe, these evolving treatment paradigms are implemented within a heterogeneous landscape of regulatory approval, reimbursement and access, resulting in important differences in care across countries. In this Series paper, we discuss contemporary systemic treatment strategies for HCC from a European perspective, focusing on treatment selection and sequencing, the role of predictive biomarkers and locoregional therapies, and disparities in access to effective treatments. Generating prospective evidence to inform treatment selection and sequencing, while ensuring more timely and equitable access to effective therapies will be essential to optimise HCC care across Europe.

This interim safety/toxicity analysis aims to assess toxicity of adjuvant stereotactic body radiation therapy (SBRT) after surgery of pancreatic cancer (PC) with high risk features across an ongoing prospective phase II trial, allowing better integration of chemotherapy and surgery. The study started in 2021 and this paper represents an interim safety analysis. Enrollment will last 36 months, followed by 12 months of follow-up for a duration of 4 years and 50 patients. Inclusion criteria are: pT1-T4 adenocarcinoma with or without positive resection margin and/or N1 at lymphadenectomy. Chemotherapy can be administered in neoadjuvant and adjuvant setting. The primary endpoint is local relapse. The secondary endpoints are disease-free survival, overall survival, patterns of failure, acute and late toxicity. Radiation dose is 40 Gy in 5 fractions. Toxicities are recorded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The study protocol was approved by the institutional research ethics committee on May 18th 2021 and registered on ClinicalTrials.gov (NCT05043857). This preliminary analysis was focused on 50 patients. The median follow-up at the time of the analyses was 16.5 months (range 3–35). Neoadjuvant chemotherapy was administered to 23 patients (46

541 Background: In HIMALAYA (NCT03298451), STRIDE (Single T Regular Interval D) improved overall survival vs sorafenib at the 3-yr and 5-yr data cutoffs (DCOs), with manageable safety. We assess baseline characteristics and safety outcomes in STRIDE-treated HIMALAYA participants (pts) who were T-rechallenged. Methods: Pts were randomized to STRIDE (T 300 mg once + D 1500 mg every 4 weeks [Q4W]), D monotherapy (1500 mg Q4W), or sorafenib (400 mg BID). Pts who, by investigator assessment, were benefitting from STRIDE but had evidence of progressive disease (of target or non-target lesions), could receive one additional dose of T 300 mg after ≥6 cycles of D. Efficacy was not assessed due to implicit survivorship bias in the cohort. In this post-hoc exploratory analysis, baseline characteristics at initial T dosing, treatment (tx) exposure, and safety are assessed in STRIDE-treated pts who were T-rechallenged. Outcomes are assessed at 3 yrs (primary DCO: Aug 27, 2021) and 5 yrs (DCO: Mar 1, 2024) of follow-up. Results: At the 3-yr DCO, 30/393 (8%) pts were T-rechallenged; at the 5-yr DCO, 34/393 (9%) pts were T-rechallenged (64 yrs median age, 85% male, 27% Asian; similar to overall study population). At the 3-yr DCO, the median (range) tx duration of D was 16.5 (5.5–42.6) months (mo) for T-rechallenged pts vs 5.5 (0.4–42.6) mo for all STRIDE pts. At the 5-yr DCO, the median (range) tx duration of D was 16.6 (5.5–72.0) mo for T-rechallenged pts vs 5.5 (0.3–72.0) mo for all STRIDE pts; the median (range) time from tx start to T rechallenge was 12.8 (4.9–53.4) mo; 44% of pts were rechallenged ≤12 mo of starting tx. Overall, T-rechallenged pts had similar safety outcomes to the overall STRIDE population. At the 3-yr DCO, adverse events (AEs) of any causality occurred in 97% of T-rechallenged pts vs 97% of all STRIDE pts (Table). No AEs with outcome of death occurred in T-rechallenged pts. Immune-mediated AEs (imAEs) occurred in 33% of T-rechallenged pts; 10% had imAEs requiring high-dose steroids. Among T-rechallenged pts, 17% had a Grade 3 or 4 treatment-related AE (TRAE) at any time (10% before and 7% after rechallenge). Serious TRAEs occurred in 6% of T-rechallenged pts vs 18% of all STRIDE pts, with no new serious TRAEs between the 3-yr and 5-yr DCOs. Conclusions: Tx was well-tolerated by T-rechallenged pts under the protocol conditions. Despite a limited cohort size, the baseline characteristics and safety outcomes were in line with the overall STRIDE population. Clinical trial information: NCT03298451 . n (%) T-rechallenged pts(n=30*) All STRIDE pts(n=388*) Any AE 29 (96.7) 378 (97.4) Grade 3/4 AE 12 (40.0) 196 (50.5) AE with outcome of death 0 30 (7.7) imAE 10 (33.3) 139 (35.8) Any TRAE 22 (73.3) 294 (75.8) TRAE pre-rechallenge 21 (70.0) - TRAE post-rechallenge 9 (30.0) - Serious TRAE by 3-yr DCO 2 (6.7) 68 (17.5) Serious TRAE by 5-yr DCO 2 (5.9) † 68 (17.5) *In the safety analysis set (all pts who received ≥1 dose of study tx). † n=34 at 5-yr DCO.

BACKGROUND AND AIMS:Atezolizumab plus bevacizumab (A+B) and STRIDE (tremelimumab plus durvalumab) represent two of the approved first-line immunotherapy strategies for unresectable hepatocellular carcinoma (HCC). As no head-to-head trial exists, we assessed temporal differences in survival benefit using complementary analytic frameworks. METHODS:Three independent analyses were conducted: (1) anchored indirect comparison using reconstructed survival from IMbrave150 and HIMALAYA; (2) a real-world A+B cohort (n = 883) weighted via MAIC to match STRIDE baseline characteristics; and (3) a propensity-matched population-level dataset from TriNetX (n = 309 per arm). Time-interval hazard ratios (HRs), RMST, and conditional landmark survival were calculated. Proportional hazards were assessed by Schoenfeld testing; pooled interval HRs were synthesized through meta-analysis. RESULTS:Across all models, A+B showed a consistent early advantage. In the first 6 months, the pooled HR favored A+B (0.75; 95% CI 0.64-0.88), with absolute survival differences of + 5-7%. From 6-12 months, HRs remained numerically favorable but non-significant. Between 12 and 24 months, pooled HRs approached neutrality (0.93-1.06), with confidence intervals crossing unity and no meaningful absolute survival differences. Beyond 24-36 months, the effect reversed in favor of STRIDE (anchored HR 1.41; RWD HR 2.52; TriNetX HR 1.47). Meta-analysis confirmed a progressive late benefit for STRIDE from 36 to 60 months (pooled HR 1.54-1.75). Schoenfeld tests indicated time-dependent effects in all frameworks (p < 0.05), and ΔRMST trajectories were highly concordant (Pearson r > 0.97). CONCLUSIONS:A+B is associated with stronger early tumor control, while STRIDE provides more durable long-term survival beyond 2-3 years. These findings support selecting therapy based on temporal treatment objectives and advocate for biomarkers predicting early versus sustained treatment benefit.

Background and Aims: The management of comorbidities has gained relevance in hepatocellular carcinoma (HCC) due to improved long-term survival. Bevacizumab, an anti-VEGF drug, increases the risk of major adverse cardiac events (MACE). Identifying at-risk patients is crucial since anti-VEGF-free therapeutic alternatives are now available. This study aimed to assess whether the European Society of Cardiology (ESC) antiangiogenic risk score and the CARDIOSOR score (Carballo-Folgoso, 2021) predict MACE in patients with HCC treated with atezolizumab/bevacizumab (AB).Methods: We retrospectively analyzed prospectively collected data from the multicentric Italian ARTE dataset, including patients treated with AB for unresectable HCC between June 2022 and July 2025. MACE occurrence was evaluated using a competing risk regression, considering non-cardiovascular death as a competing event.Results: Among 538 patients (median age 69.8 years), the prevalence of arterial hypertension and obesity was 56.3% and 18.4%, respectively. Moreover 7.6% had chronic coronary artery disease. Median follow-up was 22.4 months (95% CI 21.0-24.2 months) and median overall survival 19.7 months (95% CI 17.1-22.3). Twenty MACE (3.7%) occurred: 8 cerebrovascular accidents, 7 acute coronary syndromes, 3 strokes, and 2 heart failures. The cumulative incidence of MACE was 10.6%, 3.7%, 2.6%, and 0.7% in very high, high, medium and low risk groups according to the ESC score (sHR 3.80, 95% CI 1.52–9.45, p=0.004). Patients with a high-risk CARDIOSOR score also had an increased risk of MACE (sHR 2.70, 95% CI 1.08–6.74, p=0.03). The two scores performed similarly when we analyzed the goodness of fit achieving an Akaike and Bayesian information criteria of 235 and 239 and 241 and 245.Conclusion: These findings suggest that the ESC and CARDIOSOR scores could be used to stratify the risk of MACE in patients receiving AB. These tools might inform clinicians and provide relevant information when evaluating the choice of the first line regimen.