Background: Coronary artery bypass grafting (CABG) is a well-established revascularization strategy for patients with multivessel coronary artery disease. The effectiveness of CABG is significantly influenced by antiplatelet therapy aimed at maintaining graft patency and reducing thrombotic complications. However, substantial inter-individual variability exists in platelet function responses to standard therapies such as aspirin and clopidogrel, leading to antiplatelet resistance. This variability has been linked to increased risks of myocardial infarction, stroke, and early graft failure. Platelet function testing (PFT) offers a potential strategy to identify resistance and guide more personalized antiplatelet therapy. This study aims to evaluate the association between perioperative platelet function test results and clinical outcomes following CABG. By assessing platelet responsiveness at multiple timepoints and correlating findings with postoperative events, the study seeks to determine whether PFT can stratify risk and improve patient management. Methods: This is a prospective, single-centre, observational cohort study conducted at a tertiary NHS cardiac surgery centre. Patients having elective or urgent isolated CABG will be enrolled and undergo perioperative PFT using the TEG6s system. Clinical outcomes will be monitored for 12 months postoperatively, with primary endpoints assessing the correlation between platelet function results and major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints will include the prevalence of antiplatelet resistance, demographic predictors, and the feasibility of integrating PFT into clinical workflows. Results: This study will report the prevalence of aspirin and clopidogrel resistance in CABG patients based on TEG6s PFT, as well as the correlation between platelet function results and MACCE, postoperative bleeding, and the need for surgical re-exploration. Additionally, it will examine the associations between demographic and clinical factors—such as diabetes status, renal function, BMI, and surgical technique—and variability in platelet responsiveness. The feasibility of incorporating PFT into perioperative workflows will also be evaluated, assessing whether results could support personalized antiplatelet management in future clinical trials. Conclusions: Findings from this study will provide real-world evidence regarding platelet function variability in CABG patients and suggest that PFT may identify those at increased risk of thrombotic complications. This exploratory analysis supports the need for larger interventional trials aimed at optimizing individualized postoperative antiplatelet therapy to improve surgical outcomes.

Graphical AbstractSummary of the top 10 papers in 2024 in ischaemic heart disease. AI, artificial intelligence; AI-QCT, atherosclerosis imaging–quantitative computed tomography; ANOCA, angina with non-obstructed coronary arteries; EF, ejection fraction; FAI, fat attenuation index; FFR, fractional flow reserve; HF, heart failure; LRP, lipid-rich plaque; MACE, major adverse cardiovascular events; MLA, minimal lumen area; PB, plaque burden; PCI, percutaneous coronary intervention; QoL, quality of life; TCFA, thin cap fibroatheroma.Open in new tabDownload slide

Despite significant advances in left ventricular assist device (LVAD) technology, particularly with the HeartMate 3, hemocompatibility-related adverse events (HRAEs), especially bleeding, remain common due to complex patient-device interactions and the need for anticoagulation. This has prompted interest in exploring new and less aggressive antithrombotic strategies. Direct oral anticoagulants (DOACs) have gained attention for their predictable pharmacokinetics, fixed dosing, and lower bleeding risk in other populations. Among them, apixaban has emerged as the most extensively studied DOAC in the HeartMate 3 setting, standing out as a promising alternative to VKAs in carefully selected patients, with the potential to lower bleeding risk without compromising thrombotic protection. However, available evidence remains limited by small sample sizes, short follow-up, and selected patient populations. Important gaps persist regarding optimal dosing, timing of initiation, level monitoring, and safety in vulnerable subgroups, particularly patients awaiting heart transplantation. This review synthesizes the current evidence on DOAC use in HeartMate 3-supported patients, provides practical guidance for real-world decision-making, and highlights areas where further research is needed. Although more data are required to define its role, apixaban is increasingly positioned as a promising VKA alternative in LVAD-patients and could ultimately reshape anticoagulation practice in this population.

Background and Objective:Atrial fibrillation (AF) is an independent risk factor for ischemic stroke and systemic thromboembolism. Oral anticoagulation (OAC) effectively reduces stroke risk but also increases bleeding risk. Current clinical risk scores for bleeding in AF patients have only modest predictive ability and overlapping stroke and bleeding risk factors complicate treatment decisions. This narrative review aims to review and evaluate current evidence on biomarkers that can predict bleeding risk in AF patients on OAC and assess their integration into risk-scoring systems to guide more personalised clinical decision-making. Methods:This narrative review summarises data from major clinical trials and cohort studies evaluating bleeding-related biomarkers in AF patients on OAC, including growth differentiation factor 15 (GDF-15), high-sensitivity cardiac troponin (hs-cTn), N-terminal prohormone-brain natriuretic peptide (NT-pro-BNP), interleukin-6 (IL-6), von Willebrand factor (vWF), cystatin C, and D-dimer. The prognostic value of these biomarkers, their role in risk scores (e.g., ABC-bleeding), and their ability to improve predictive accuracy were examined. Key Content and Findings:In recent years, several biomarkers have shown promise in predicting bleeding risk in patients with AF on OAC. GDF-15 has consistently emerged as a strong independent marker of significant bleeding and mortality, validated in trials such as Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY), Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE), and Edoxaban Versus Warfarin in Patients with Atrial Fibrillation trial (ENGAGE AF-TIMI 48). hs-cTn and D-dimer levels are also independently associated with an increased bleeding risk and have been included in the ABC-bleeding score, which has shown superior predictive ability compared to traditional scores, such as HAS-BLED. Biomarkers such as cystatin C, which reflects renal dysfunction, vWF, and IL-6 have demonstrated associations with adverse outcomes, although their predictive abilities vary. The inclusion of these biomarkers in clinical tools has improved bleeding risk prediction. Although trials and cost-effectiveness models suggest clinical benefit, further real-world validation is required to confirm their place in everyday clinical practice. Conclusions:Several biomarkers have demonstrated the ability to predict bleeding risk in patients with AF. Risk-scoring systems that incorporate biomarkers have improved the prediction of bleeding events. More accurate identification of patients at higher risk of bleeding allows clinicians and patients to better balance the risks of bleeding versus stroke in the setting of AF and create individualised care plans to lower the overall rate of both stroke and bleeding.

BACKGROUND AND OBJECTIVES:In patients with mechanical heart valves (MHVs), anticoagulation (AC) interruption after intracranial hemorrhage (ICH) poses a clinical dilemma because of competing risks of ischemic complications and hemorrhagic recurrence. To date, the optimal timing for resuming vitamin K antagonists (VKAs) remains unclear. The aim of this meta-analysis was to quantify the risks of ischemic stroke and recurrent ICH associated with VKA resumption in this population and explore the temporal risk dynamics. METHODS:We systematically searched PubMed, Embase, and Cochrane Library from inception to December 2023 for studies reporting ischemic or hemorrhagic outcomes in adults with MHVs who experienced ICH and were considered for VKA resumption. Primary outcomes were ischemic stroke before AC resumption and recurrent ICH after AC resumption. Random-effects meta-analyses were performed. Meta-regressions assessed whether timing of resumption influenced risk. Risk trajectories were estimated using a model-based approach. RESULTS:Nine studies were included, comprising 435 patients with MHVs with confirmed ICH included in the pooled analysis. The mean age ranged from 54.1 to 75 years; 31.3% were female. The pooled incidence of recurrent ICH after AC reinitiation was 11.4% (95% CI 8.2-15.6; I2 = 0%), the incidence of ischemic stroke during AC suspension was 6.1% (95% CI 4.1-8.9; I2 = 0%), valve thrombosis occurred in 3.3% (95% CI 1.9-5.6; I2 = 0%), and mortality occurred in 4.9% (95% CI 2.0-11.5; I2 = 37%). Meta-regression demonstrated a significant inverse association between time to AC resumption and risk of recurrent ICH (regression coefficient -0.039; 95% CI -0.093 to 0.015; p = 0.13), corresponding to an approximate 50% relative reduction in risk at 11 days after ICH. No significant time-dependent association was observed for ischemic stroke (coefficient -0.013; 95% CI -0.065 to 0.039; p = 0.61). DISCUSSION:In patients with MHVs who experienced an ICH, this meta-analysis found that resumption of AC was associated with a recurrent ICH rate of 11.4% and an ischemic stroke rate of 6.1% during AC suspension. Meta-regression suggested a lower risk of recurrent ICH with later AC resumption, with a potential risk reduction at approximately 11 days after ICH. No time-dependent increase in ischemic stroke was observed. Limitations include the retrospective design of most studies and heterogeneous AC timing across cohorts.

According to the ESC guidelines, cangrelor may be considered in P2Y12-inhibitor-naïve acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The aim of this review is to summarize available evidence on the optimal maintenance therapy with P2Y12 receptor inhibitor after cangrelor. Transitioning from cangrelor to a thienopyridine, but not ticagrelor, can be associated with a drug-drug interaction (DDI); therefore, a ticagrelor loading dose (LD) can be given any time before, during, or at the end of a cangrelor infusion, while a LD of clopidogrel or prasugrel should be administered at the time the infusion of cangrelor ends or within 30 minutes before the end of infusion in the case of a LD of prasugrel. Administration of any oral antiplatelet agent at the end of a cangrelor infusion will also result in a transient period of increased platelet reactivity. The inter-individual variability of this period is difficult to predict because it depends on many factors related to the patient and the treatment. In addition, experimental studies indicate that cangrelor may exert a cardioprotective effect beyond the blockade of platelet aggregation. Considering the available data, the potential use of cangrelor in ACS patients goes well beyond the current indications. Furthermore, we believe that it might be prudent to avoid use of thienopyridines during and soon after a cangrelor infusion until conclusive data on the effect of the DDI on the clinical outcome are available. On the other hand, ticagrelor seems to be an optimal oral agent for continuation of P2Y12 inhibition in patients receiving cangrelor infusion.

The 2023 ESC guidelines changed previously recommended a strategy of early treatment in patients with STEMI. Pre-treatment with a P2Y12 receptor inhibitor may be considered in patients undergoing a primary PCI strategy (Class IIb, Level of evidence B). However, the available scientific evidence justifies a personalized approach differentiating the indications for pre-treatment with oral P2Y12 receptor inhibitors depending on the concomitant administration of opioids. In our opinion, in patients undergoing primary PCI not treated with opioids, pre-treatment with an oral P2Y12 receptor inhibitor should be applied, while in patients undergoing primary PCI treated with opioids, pre-treatment with an oral P2Y12 receptor inhibitor should be considered.

BACKGROUND:Efficient dual antiplatelet therapy is crucial in reducing adverse cardiovascular events in patients with acute coronary syndrome (ACS). Comparative effectiveness between clopidogrel, prasugrel, and ticagrelor remains unclear in real-world settings. AIMS:The objective was to evaluate one-year clinical outcomes in ACS patients treated with clopidogrel, prasugrel, or ticagrelor using data from the Polish Registry of Acute Coronary Syndromes (PL-ACS). MATERIAL AND METHODS:This retrospective cohort study analyzed 381 278 ACS patients from the PL-ACS registry from 2009 to 2022, who were treated with clopidogrel, prasugrel, or ticagrelor during hospitalization with a 12-month consistent regimen. The primary outcome was one-year all-cause mortality. Secondary outcomes included a composite of death, myocardial infarction, or stroke, and the net clinical outcome, a composite of all-cause death, myocardial infarction, stroke, and bleeding. Propensity score matching was applied to reduce confounding factors. Cox proportional hazards models were used for analysis. RESULTS:Of 381 278 ACS patients, 332 338 (87.2%) were treated with clopidogrel, 5312 (1.4%) with prasugrel, and 43 628 (11.4%) with ticagrelor. After propensity score matching, prasugrel and ticagrelor reduced mortality compared with clopidogrel (hazard ratios 1.69 and 1.72, respectively; P <0.0001). Ticagrelor also showed superior net clinical outcomes compared with both prasugrel and clopidogrel. CONCLUSIONS:This large-scale study confirms better clinical outcomes of dual antiplatelet therapy with prasugrel or ticagrelor compared to clopidogrel in ACS, with ticagrelor demonstrating superiority over prasugrel in terms of net clinical outcome. Despite the high clopidogrel usage rate in Poland, these findings support the preference for ticagrelor or prasugrel in ACS.

BACKGROUND:Direct transcatheter aortic valve implantation (TAVI) approach is feasible and safe compared to predilatation-TAVI. Certain clinical and computerized tomography (CT)-based characteristics might indicate the need for balloon aortic valvuloplasty (BAV) before TAVI, especially with self-expanding valves. AIMS:We aimed to identify patients who require predilatation before TAVI. METHODS AND RESULTS:We performed a retrospective, single-center study between 2020 and 2024, enrolling 315 patients (predilatation = 158 vs. direct = 157) aged 81 ± 6 years, 43.5% male, with EuroSCORE II of 3.7 ± 2.9. The rate of predilatation increased over the study period and was performed more often in patients with higher velocity and pressure gradients on echocardiography, higher aortic valve calcium score on CT, bicuspid morphology, bigger aortic annulus anatomy, severe aortic cusp calcification, tortuous descending aorta (bend > 60°), and horizontal ascending aorta (angle > 50°). Direct implantation was performed more frequently in patients with permanent pacemaker, ischemic heart disease, concomitant significant aortic regurgitation, or alternative-access TAVI. Regression analysis demonstrated that only the horizontal aorta was an independent predictor of predilatation (p = 0.037). The rates of valve recapture, embolization, contrast use, procedure duration, hospital stay, inpatient death, stroke, significant paravalvular leak on postprocedural echocardiography, and new pacemaker implantation were not different between the groups. The rate of BARC ≥ 3 bleeding, mainly due to access-site complications, was more frequent with direct-TAVI compared to predilatation (6.4% vs. 0.6%; p = 0.005). CONCLUSIONS:Both predilatation and direct-TAVI approaches can be safely performed in routine practice. Upfront selection of either approach based on the patient characteristics, echocardiography gradients, and CT anatomical features is recommended.

Atrial fibrillation (AF) increases the risk of ischemic stroke (IS) and systemic embolism, necessitating thromboprophylaxis with direct oral anticoagulants (DOAC), which increase bleeding. Drugs that inhibit factor XI (FXI) have been developed to provide thromboprophylaxis with lower bleeding risk. We performed a systematic review and meta-analysis of randomised controlled trials comparing FXI inhibitors versus DOAC in patients with AF, reporting primary outcomes of International Society of Thrombosis and Haemostasis (ISTH) major bleeding or clinically relevant non-major bleeding (CRNMB), and exploratory outcomes of ischaemic stroke (IS), intracranial hemorrhage (ICH) and death. Three trials were identified. The PACIFIC-AF (Phase 2) and OCEANIC-AF (Phase 3) trials compared asundexian, an oral, small-molecule FXIa inhibitor, with apixaban. AZALEA-TIMI 71 (Phase 2) compared abelacimab, a subcutaneous monoclonal antibody against FXI/FXIa, with rivaroxaban. FXI inhibitors reduced the composite of major bleeding or CRNMB (pooled-OR 0.39, 95

Suboptimal care for ST-elevation myocardial infarction (STEMI) in low- and middle-income countries is a significant problem. Registries from Latin America, Africa, and Asia show that <65% of patients receive reperfusion therapy, and widespread treatment delays and a lack of access to optimal therapies lead to preventable deaths and complications. While current guidelines provide a blueprint for care, their implementation in low-resource settings requires specific guidance that considers geographical, logistical, and economic realities. This clinical consensus offers a new framework for developing STEMI care systems in these countries. We propose a flexible, three-model pathway, based on the initiatives such as STEMI India and Stent - Save a Life. The models include a fibrinolysis model, a pharmaco-invasive strategy model, and a primary percutaneous coronary intervention (PCI) model. This approach emphasizes adaptability, allowing local STEMI systems to be tailored to specific circumstances. The framework also addresses specific, common challenges, such as delayed access to primary PCI, reperfusion in patients with cardiogenic shock and expected delayed PCI, fibrinolysis in patients with a high risk of bleeding, and the absence of fibrin-specific fibrinolytics, catheterization labs, or reperfusion therapies at all. The consensus also highlights the importance of continuous improvement, patient education, and adopting secondary prevention strategies. Ultimately, this framework is designed to help healthcare providers and leaders in developing countries improve their regional STEMI care systems.

Immobility following orthopedic surgery is a risk factor for venous thromboembolism (VTE), but the optimal duration of anticoagulant thromboprophylaxis remains controversial. The protocol of the “Enhanced Recovery and Abbreviated Length of Anticoagulation for Thromboprophylaxis After Primary Hip Arthroplasty” (ENABLE-Hip) is presented, an investigator-initiated randomized double-blind trial, comparing shorter anticoagulant duration with standard-of-care. To improve outcomes after complex thrombotic events, a novel multidisciplinary approach is presented, based loosely on the tumor board model from oncology, with establishment of a “Clot Cases Conference”. East Asians are more susceptible to bleeding than other ethnicities, with sub-standard dose direct oral anticoagulant (DOAC) frequently prescribed. A meta-analysis evaluating Japanese patients with AF shows that patients receiving underdosed DOACs have fewer bleeding events, similar thromboembolic events, but an increase in all-cause mortality, possibly due to increased frailty. In terms of biomarkers, transforming growth factor-β1, a cytokine that can promote VTE, was shown in patients with pulmonary embolism to be associated with residual pulmonary vascular obstruction. Although monocytes have traditionally been classified into three subsets, expression of recently described Mon4 is reported to be a marker of cardiovascular risk following acute myocardial infarction (AMI). The benefit of carotid endarterectomy for moderate carotid artery stenosis (CAS) is unclear. In patients with minor stroke and moderate ipsilateral CAS (50–69

Stroke is a devastating and underdiagnosed complication in patients with cardiogenic shock (CS) supported by temporary mechanical circulatory support (tMCS). Stroke occurs in approximately 1 to 4% of patients on microaxial flow pumps and 6 to 7% of those on veno-arterial extracorporeal membrane oxygenation, though the true incidence is likely higher due to diagnostic limitations in sedated and critically ill patients. The occurrence of stroke in this population significantly worsens clinical outcomes, increasing morbidity, mortality, and healthcare resource utilization. This review outlines the risk factors and mechanisms underlying both ischaemic and haemorrhagic stroke in patients receiving tMCS. It explores how the aetiology of CS, the choice of tMCS device, anticoagulation strategies, and cellular injury contribute to stroke risk. The pathophysiology in this setting is multifactorial and often dual-edged, driven by haemolysis, platelet dysfunction, endothelial disruption, and immune-mediated thrombogenesis. Concurrently, bleeding complications arise from acquired von Willebrand syndrome, thrombocytopenia, and dysregulated fibrinolysis. Currently, there are no evidence-based guidelines for managing bleeding and thrombotic complications in patients on tMCS, largely due to the lack of robust data. Consequently, clinical practices vary, and treatment decisions often require navigating a complex balance between thrombosis and bleeding without high-quality evidence to guide care. This review highlights the key physiological and pathological changes associated with tMCS to inform strategies for stroke prevention, early detection, and management. Developing standardised protocols through prospective studies is essential to improving outcomes in this high-risk population.

AIMS:Cardiologists have only had rare exposure to haemophilia patients and patients with other congenital bleeding disorders during the last decades, as these patients had a reduced life expectancy and were partly protected against thrombosis due to the bleeding disorder. With the availability of effective and safe replacement therapies of clotting factors, the average life expectancy in these populations of patients has significantly increased, and thrombotic complications may occur. METHODS AND RESULTS:The European Society of Cardiology Working Group on Thrombosis has taken the initiative to broaden the spectrum of these haematological conditions to include patients with a larger variety of congenital bleeding disorders with concomitant cardiac conditions as compared to a recent position paper by the European Haematology Association in collaboration with other societies (ISTH, European Association for Haemophilia and Allied Disorders, and ESO). Management of antithrombotic therapy or thromboprophylaxis in these individuals is challenging due to the wide phenotypes encompassed by congenital bleeding disorders. These include abnormalities in both primary haemostasis (involving von Willebrand factor and platelet function) and secondary haemostasis (related to coagulation factors and fibrinogen). Bleeding disorders range from mild to very severe. Based on existing literature, we provide clinical consensus statements on optimizing antithrombotic treatment strategies for patients with congenital bleeding disorders and highlight the current gaps in knowledge in these complex clinical settings. CONCLUSION:Of importance, an individualized approach to antithrombotic therapy is warranted to properly balance the two risks of thrombosis and bleeding. Adoption of the safest interventional techniques, reduction of the intensity and/or duration of antithrombotic therapies, and attention to the safe levels of clotting factors is generally advised.

Background In patients undergoing percutaneous coronary intervention (PCI), the use of anti-inflammatory therapy with colchicine is associated with a reduction of recurrent ischemic events. The mechanisms of such findings are not fully elucidated. Objectives To investigate the effects of colchicine versus aspirin on inflammation and platelet reactivity in patients with acute coronary syndrome (ACS) undergoing PCI. Methods This observational study compared laboratory measurements in ACS patients receiving single antiplatelet therapy with ticagrelor or prasugrel plus colchicine (MACT) ( n = 185) versus conventional dual-antiplatelet therapy (DAPT) with aspirin plus ticagrelor or prasugrel ( n = 497). The primary outcome was the frequency of high residual inflammation, defined as high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L at 1 month post-PCI. Multiple sensitivity analyses were performed for the primary outcome, including multivariable adjustment, propensity-score matching, and inverse-probability weighted methods. Results One month after PCI, patients treated with MACT had significantly lower levels of hs-CRP compared to those treated with DAPT (0.6 [0.4–1.2] vs. 0.9 [0.6–2.3] mg/L, p < 0.001). The frequency of high residual inflammation was also lower in the MACT group (10.8% vs. 27.2%, p < 0.001) (odds ratio [95% confidence interval] = 0.33 [0.20–0.54], p < 0.001). This effect was consistent across sensitivity analyses. There was no difference in platelet reactivity between MACT and DAPT (49.6 ± 49.0 vs. 51.5 ± 66.4 P2Y 12 reaction unit [PRU] measured by VerifyNow, p = 0.776). Conclusion In ACS patients undergoing PCI, MACT was associated with a lower rate of high residual inflammation without increasing platelet reactivity compared to conventional DAPT. Clinical trial registration NCT04949516 for MACT pilot trial and NCT04650529 for Gyeongsang National University Hospital registry.

Graphical AbstractOpen in new tabDownload slidePlatelet activation by exposure of plaque constituents and high shear forces, together with activation of coagulation, result in thrombus formation. This triggers simultaneous activation of endogenous fibrinolysis, and this, together with the effects of flow, may prevent vessel occlusion or restore vessel patency following thrombotic occlusion.

Current evidence indicates that dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor is essential for the prevention of thrombotic events after percutaneous coronary interventions. However, dual antiplatelet therapy is associated with increased bleeding which may outweigh the benefits. This has set the foundations for customizing antiplatelet treatments to the individual patient. However, bleeding and ischemic risks are often present in the same patient, making it difficult to achieve this balance. The fact that oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) have diverse pharmacodynamic profiles that affect clinical outcomes supports the rationale for using platelet function and genetic testing to individualize antiplatelet treatment regimens. Indeed, up to one-third of patients treated with clopidogrel, but a minority of those treated with prasugrel or ticagrelor, exhibit high residual platelet reactivity resulting in an increased thrombotic risk. On the other hand, prasugrel and ticagrelor are frequently associated with low platelet reactivity and increased bleeding risk compared with clopidogrel without providing any additional reduction in ischemic events compared with patients who adequately respond to clopidogrel. The use of platelet function and genetic testing may allow for a guided selection of oral P2Y12 inhibitors. However, the nonuniform results of randomized controlled trials have led guidelines to provide limited recommendations on the implementation of these tests in patients undergoing percutaneous coronary intervention. In light of recent advancements in the field, this consensus document by a panel of international experts fills in the guideline gap by providing updates on the latest evidence in the field as well as recommendations for clinical practice.

Obesity and underweight are a growing health problem worldwide and a challenge for clinicians concerning antithrombotic therapy, due to the associated risks of thrombosis and/or bleeding. This clinical consensus statement updates a previous one published in 2018, by reviewing the most recent evidence on antithrombotic drugs based on body size categories according to the World Health Organization classification. The document focuses mostly on individuals at the extremes of body weight, i.e. underweight and moderate-to-morbid obesity who require antithrombotic drugs, according to current guidelines, for the treatment or prevention of cardiovascular diseases or venous thromboembolism. Managing antithrombotic therapy or thromboprophylaxis in these individuals is challenging, due to profound changes in body composition, metabolism and organ function, altered drug pharmacokinetics and pharmacodynamics, as well as weak or no evidence from clinical trials. The document also includes artificial intelligence simulations derived from in silico pharmacokinetic/pharmacodynamic models, which can mimic the pharmacokinetic changes and help identify optimal regimens of antithrombotic drugs for severely underweight or severely obese individuals. Further, bariatric surgery in morbidly obese subjects is frequently performed worldwide. Bariatric surgery causes specific and additional changes in metabolism and gastrointestinal anatomy, depending on the type of the procedure, which can also impact the pharmacokinetics of antithrombotic drugs and their management. Based on existing literature, the document provides consensus statements on optimising antithrombotic drug management for underweight and all classes of obese patients, while highlighting the current gaps in knowledge in these complex clinical settings, which require personalized medicine and precision pharmacology.