Antithrombotic Therapy Research Articles

Factor XI inhibitors – Rising stars in anti-thrombotic therapy?

The “holy grail” of preventing and treating thrombosis and thromboembolism would be a drug that was highly effective (preventing clots) and at the same time had a low risk of bleeding. From a hemostasiological perspective, the inhibition of factor XI represents a promising target because a reduced level of factor XI protects against thrombosis without significantly increasing the risk of spontaneous bleeding.Currently, three different classes of drugs of factor XI-inhibition are tested. These are (1) monoclonal antibodies (mAbs), (2) so-called synthetic, small molecules and (3) antisense oligonucleotides (ASOs). This article provides a narrative overview of the current status of studies on all three classes of drugs.Tests with mAbs have been conducted primarily in DVT prevention after knee replacement surgery. One large phase 3 study is testing the mAbs Abelacimab in patients with atrial fibrillation. The synthetic, small molecules Asundexian and Milvexian are tested in several phase 3 trials, mainly in patients with non-cardioembolic ischemic stroke. Results can be expected in the coming years. Clinical testing of ASOs to inhibit factor XI are still in their infancies.

Impact of Post-Procedural Atrial Fibrillation on Anti-Thrombotic Therapy After Percutaneous Patent Foramen Ovale Closure

Impact of Post-Procedural Atrial Fibrillation on Anti-Thrombotic Therapy After Percutaneous Patent Foramen Ovale Closure

Perioperative Management of Antiplatelet and Anticoagulation in Brain Tumor Surgery: A Survey of International Practices

Perioperative management of antithrombotic therapy is a necessary preprocedural consideration for patients prescribed direct oral anticoagulants (DOACs), vitamin K antagonists, or antiplatelet medications. There is a lack of evidence-based guidelines to help inform decision-making in managing antiplatelet and anticoagulation medications in the perioperative period around brain tumor resection. The objective of this study was to provide an example of the heterogeneity in practice and raise awareness for the need to create standardized guidelines for managing these medications. A survey was sent to a list of over 800 international neurosurgeons who are members of the Neurosurgery Research Listserv. The survey comprised 70 questions assessing individual practices for managing thromboprophylaxis, antiplatelet medications, and anticoagulation in the perioperative period. The survey was sent via e-mail invitation between March 2021 and June2021. A total of 72 surgeons responded to the survey. There was no difference in medication management preoperatively or postoperatively when comparing intra- and extra-axial tumor resections. Cessation of antiplatelet medications varied between 3 and 11 days while restart varied between 1 and 14 days. Preoperative management of vitamin K antagonists varied between indication for use (P < 0.001) while DOAC management did not. In our group of respondents, 90% started heparin products within 5 days of surgery, while the same fraction restarted DOAC within 14 days. Respondents demonstrated significant heterogeneity in their perioperative management of antiplatelet and anticoagulation medication in brain tumor resection. This may lead to an unacceptable level of heterogeneity in practice that has the potential to cause patient harm due to errors in medication management.

Antithrombotics alter intracerebral hemorrhage presentation without affecting minimally invasive endoscopic evacuation

ObjectivesIntracerebral hemorrhages are associated with significant morbidity and mortality. While the ENRICH trial supports the efficacy of surgical evacuation for lobar hemorrhages, the impact of antithrombotic therapies on minimally invasive surgery outcomes remains unexplored. This study evaluates the effects of chronic anticoagulants and antiplatelets on the technical and longterm outcomes of minimally invasive intracerebral hemorrhage evacuation. Materials and MethodsA prospectively collected registry of patients undergoing minimally invasive surgery for intracerebral hemorrhage from a single institution was analyzed (December 2015-September 2022). Data included key demographics, comorbidities, antithrombotic/reversal status, presenting clinical/radiographic characteristics, procedural metrics, and clinical outcomes. Patients were divided into control (neither therapy), antiplatelet-only, and anticoagulant-only groups, with antiplatelet/anticoagulant reversals conducted per current American Heart Association/American Stroke Association guidelines. Variables significant in univariate analyses (p<0.05) were advanced to multivariable regression models. ResultsAmong 226 intracerebral hemorrhage patients treated with minimally invasive surgery, 41% (N=93) had antithrombotic medication history; 28% (N=64) received antiplatelets, and 9% (N=21) received anticoagulants. Patients on both therapies (N=6) were excluded. The antiplatelet group presented more frequently with lobar hemorrhages (56% vs. 37%; p=0.022), while patients on anticoagulants showed increased rates of intraventricular hemorrhage co-presentation (62% vs. 46%; p=0.011) compared to controls. Despite univariate analyses showing a higher postoperative hematoma volume (3.9 vs. 2.9 milliliters; p=0.020) and lower evacuation percentage (88% vs. 92%; p=0.019) for the antiplatelet group, and longer procedures for patients on anticoagulants (2.3 vs. 1.7 hours; p=0.042) compared to control, multivariable analyses indicated that antiplatelets and anticoagulants had no significant impact on these technical outcomes. Longitudinally, antithrombotics were not associated with increased rebleeding, less frequent discharge to home, lower 30-day mortality, or worse, 6-month Modified Rankin Scale scores. ConclusionsPatients on chronic antiplatelets and anticoagulants exhibited characteristic intracerebral hemorrhage phenotypes without worse technical or long-term outcomes after minimally invasive intracerebral hemorrhage evacuation, suggesting the procedure's safety for these patients.

Management of Patients Treated With Oral Anticoagulant Therapy Undergoing Percutaneous Coronary Intervention With Stent Implantation: The PERSEO Registry.

In patients on oral anticoagulant (OAC) therapy undergoing percutaneous coronary intervention (PCI) with stent, international guidelines endorse the use of direct oral anticoagulants (DOAC) rather than vitamin K antagonists (VKA) and dual antithrombotic therapy (DAT) rather than triple antithrombotic therapy (TAT). The aim of this study was to evaluate contemporary real-world data on antithrombotic regimens and outcome in patients on OAC undergoing PCI with stent. Consecutive patients on OAC undergoing PCI were enrolled in the multicenter, prospective, observational PERSEO registry (NCT03392948). Primary end point was net adverse clinical events (NACE) with VKA versus DOAC, whereas a secondary prespecified end point was NACE with DAT versus TAT both at 1-year follow-up. From February 2018 to February 2022; in total, 1234 consecutive patients were included. The main indication for OAC was atrial fibrillation (86%), and the mean CHA 2 DS 2 VASc and HAS-BLED scores were 4 ± 2 and 3.6 ± 1, respectively. Of the 1228 patients discharged alive, 222 (18%) were on VKA and 1006 (82%) on DOAC ( P < 0.01). DAT was employed in 197 patients whereas TAT in 1028. At follow-up, NACE rate was significantly higher than VKA compared with DOAC (23% vs. 16%, P = 0.013) and confirmed after propensity score adjustment. TAT and DAT did not differ as regards NACE rate (17% vs. 19%, P = 0.864) although, compared with TAT, DAT was associated with less major bleedings (2% vs. 5%, P = 0.014), confirmed after propensity score adjustment. In conclusion, in patients on OAC undergoing PCI, DOAC, compared with VKA, was associated with a significantly lower occurrence of NACE and DAT reduced bleedings compared with TAT.

Mechanisms and management of thrombosis in cancer: focus on gastrointestinal malignancies.

Cancer patients have an increased risk of venous thromboembolism (VTE) which is their second cause of death after disease progression itself. Several thrombotic risk factors coexist in cancer patients, including the ability of both cancer and tumoral microenvironment's cells to directly or indirectly activate platelets and the enzymes of the coagulation cascade, resulting in a hyper-coagulable state of blood. This narrative review gives an overview of the main mechanisms leading to VTE in cancer patients, including the role that platelets and the clotting proteins may have in tumor growth and metastasis. Noteworthy, the haemostatic balance is altered in cancer patients who may, next to a thrombosis tendency, also have an increased risk of bleeding. To highlight the complexity and the precariousness of the haemostatic balance of these patients, we discuss two specific gastrointestinal malignancies: hepatocellular carcinoma, which is frequently associated with liver cirrhosis, a condition that causes profound alterations of haemostasis, and colorectal cancer, which is characterized by a fragile mucosa that is prone to bleeding. Understanding the molecular mechanisms of cancer-associated thrombosis may give a unique opportunity to develop new innovative drugs, acting differently on distinct pathways and potentially allowing to reduce the risk of bleeding related to antithrombotic therapies. Significance Statement The topic is significant because understanding the molecular mechanisms leading to cancer associated thrombosis and bleeding, focusing on gastrointestinal malignancies, enables the development of more rationale and innovative antithrombotic strategies for cancer associated thrombosis. Eventually, this will support an improved and patient-tailored antithrombotic management in vulnerable oncologic patients.

Debates Surrounding the Use of Antithrombotic Therapy in Hemophilic Patients with Cardiovascular Disease: Best Strategies to Minimize Severe Bleeding Risk.

Navigating through antithrombotic therapy in patients with both hemophilia and cardiovascular pathology presents a complex scenario with inherent challenges and opportunities. The presence of hemophilia, characterized by impaired blood clotting, adds a layer of complexity to the management of cardiovascular conditions requiring antiplatelet therapy and anticoagulation. Striking a delicate balance between the necessity for antithrombotic treatment to prevent cardiovascular events and the heightened risk of severe bleeding in individuals with hemophilia demands a nuanced and carefully considered approach. The challenges revolve around identifying an optimal therapeutic strategy that effectively mitigates cardiovascular risks without exacerbating bleeding tendencies. In hemophilic patients with cardiovascular disease, the decision to use antiplatelet therapy requires careful consideration of the individual's bleeding risk profile, considering factors such as the severity of hemophilia, history of bleeding episodes, and concurrent medications. The goal is to provide effective antithrombotic treatment while minimizing the potential for excessive bleeding complications. Conventional anticoagulants like warfarin pose difficulties due to their potential to increase the risk of bleeding. On the other hand, emerging options like novel direct oral anticoagulants (DOACs) present an opportunity, offering predictable pharmacokinetics and user-friendly administration. However, a comprehensive exploration of their safety and efficacy in hemophilic patients is imperative. Achieving the right equilibrium between preventing cardiovascular events and minimizing bleeding risk is pivotal in selecting the most effective therapeutic option for individuals with hemophilia and cardiovascular pathology. A multidisciplinary approach, integrating the expertise of hematologists and cardiologists, becomes essential to customize treatments and address the intricacies of this medical challenge.

Antithrombotic therapy at discharge and prognosis in patients with chronic coronary syndrome and atrial fibrillation who underwent PCI: a real-world study

BackgroundThis study aimed to describe the status of antithrombotic therapy at discharge and prognosis in patients with atrial fibrillation (AF) and chronic coronary syndrome (CCS) who underwent percutaneous coronary intervention (PCI).MethodsThis was an observational, prospective study. The primary endpoint was major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke/transient ischemic attach (TIA), systemic embolism or ischemia-driven revascularization. Bleeding events were collected according to the Thrombolysis in Myocardial Infarction (TIMI) criteria.ResultsBetween 2017 and 2019, a cohort of 516 patients (mean age 66, [SD 9], of whom 18.4% were female) with AF and CCS who underwent PCI were evaluated, with a median followed-up time of 36 months (Interquartile range: 22–45). MACE events occurred in 13.0% of the patients, while the TIMI bleeding events were observed in 17.4%. Utilization of TAT (triple antithrombotic therapy) (P < 0.001) and oral anticoagulation (OAC) therapy (P < 0.001) increased through years. History of heart failure (HF) (Hazard ratio [HR], 1.744; 95% confidence interval [CI], 1.011–3.038) and TAT (HR, 2.708; 95%CI, 1.653–4.436) had independent associations with MACE events. OAC (HR, 10.378; 95%CI, 6.136–17.555) was identified as a risk factor for bleeding events. A higher creatine clearance (HR, 0.986; 95%CI, 0.974–0.997) was associated with a lower incidence of bleeding events.ConclusionsAntithrombotic therapy has been improved among patients with AF and CCS who underwent PCI these years. History of HF and TAT were independently associated with MACE events. Higher creatine clearance was protective factor of bleeding events, while OAC was a risk factor for TIMI bleeding events.

Prevalence of Ischemic Versus Hemorrhagic Stroke in Patients Taking Anti-Coagulation Therapy

OBJECTIVE: To evaluate the prevalence of ischemic versus hemorrhagic stroke in patients taking anti-coagulation therapy. PATIENTS AND METHODS: This cross-sectional prospective study was conducted at medicine Departments of Peoples University of Medical &amp; Health Sciences (PUMHS), for a period of 18 months from September 2021 to January 2023. All the patients taking anti-thrombotic therapy (warfarin, rivaroxaban, dabigatran, or apixaban) were included in this study and their baseline and clinical data were collected. Statistical package for the social sciences version (SPSS v. 26) was used for data entry and data analysis. Chi-square test/fisher’s exact and independent t-test test was used for determination of risk factors associated with hemorrhagic or ischemic strokes. A p value of &lt;0.05 was considered as statistically significant. RESULTS: A total of 296 patients were enrolled for final analysis. The overall mean age, BMI, and duration of anticoagulation therapy was 62.14±8.44 years, 25.38±3.19 kg/m2, and 8.34±12.51 months. Among all study participants, 57.43% (n = 170) were taking NOACs while 42.56% (n = 126) were taking warfarin. The overall prevalence of stroke was 14.18% (n = 42) and among them hemorrhagic stroke was more common (57.14%, n = 27) than ischemic stroke (35.71%, n = 15). Patients taking NOACs were more likely to have hemorrhagic stroke as compared to ischemic stroke, 74.07% (n = 20/27) and 40.0% (n = 7), respectively, p value &lt;0.001. CONCLUSION: The risk of stroke is quite high in patients receiving anti-thrombotic therapies. Hemorrhagic stroke is higher in patients receiving NOACs KEYWORDS: Anti-thrombotic therapy, ischemic stroke, hemorrhagic stroke, Pakistan

Antithrombotic Therapy in Cancer Patients with Cardiovascular Diseases: Daily Practice Recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO) and the Society for Thrombosis and Hemostasis Research (GTH e.V.).

Active cancer by itself but also chemotherapy is associated with an increased risk of cardiovascular disease (CVD) and especially coronary artery disease (CAD) and atrial fibrillation (AF). The frequency of CVD, CAD, and AF varies depending on comorbidities (particularly in older patients), cancer type, and stage, as well as the anticancer therapeutic being taken. Many reports exist for anticancer drugs being associated with CVD, CAD, and AF, but robust data are often lacking. Because of this, each patient needs an individual structured approach concerning thromboembolic and bleeding risk, drug-drug interactions, as well as patient preferences to evaluate the need for anticoagulation therapy and targeting optimal symptom control. Interruption of specific cancer therapy should be avoided to reduce the potential risk of cancer progression. Nevertheless, additional factors like thrombocytopenia and anticoagulation in the elderly and frail patient with cancer cause additional challenges which need to be addressed in daily clinical management. Therefore, the aim of these recommendations is to summarize the available scientific data on antithrombotic therapy (both antiplatelet and anticoagulant therapy) in cancer patients with CVD and in cases of missing data providing guidance for optimal careful decision-making in daily routine.

To stop or not to stop novel oral anticoagulants prior to performing joint interventional maneuvers? Evidence from a prospective study that the therapy can be maintained.

Anticoagulation is common in patients undergoing routine musculoskeletal interventional maneuvers. Previous retrospective studies have established the safety of continuing anticoagulation with novel oral anticoagulants (NOACs) when performing this kind of interventions. Indeed, ultrasound (US)-guided interventional maneuvers have shown a superior safety profile compared to blind anatomical maneuvers. To evaluate prospectively the periprocedural bleeding events in NOAC-anticoagulated patients undergoing interventional articular or periarticular procedures. Consecutive patients diagnosed with inflammatory or degenerative rheumatologic pathology requiring interventional maneuvers were prospectively recruited. Group 1 was treated with NOACs, group 2 was treated with vitamin K antagonists, and group 3 was not anticoagulated. Prior to the international maneuver, NOAC therapy was continuously administered, in regimens dictated by the underlying anticoagulation indication. Demographics, comorbidities, laboratory parameters, locally administered medication (corticosteroids or viscosupplementation), interventional maneuver location, needle size, and local bleeding events were recorded. Post-procedural control was performed at 30 min, 48 h, and 7 days. No articular/periarticular bleeding event occurred in patients treated with NOACs, regardless of their type and dosage, locally administered medication, needle size, location, and number of interventions per individual. Several patients in all groups developed small superficial ecchymoses at the injection site. Our results suggest that NOACs are safe to be used in a continuous regimen prior to US-guided injections, even as dual antithrombotic therapy (in combination with aspirin). The use of lower gauge needles, chosen for viscosupplementation therapy, was not burdened with adverse effects on the procedural outcome. Key Points • Currently, no prospective studies have been performed to establish the safety of continuous NOAC anticoagulation when performing routine intra- or periarticular interventional maneuvers. • The study offers an extensive view on a wide spectrum of intra- and periarticular interventional maneuvers including anatomic targets and needle sizes that were not previously assessed. • The study offers a perspective into performing repetitive maneuvers in the same patient, both over a short time and at longer intervals. • The zero periprocedural bleeding risk observed in our study may reassure practitioners and suggest that US-guided interventional therapeutic interventions are safe in patients treated with a continuous regimen of different NOACs.

Integrated proteomic and metabolomic profiling of lymph after trauma-induced hypercoagulopathy and antithrombotic therapy

BackgroundRoutine coagulation tests are not widely accepted diagnostic criteria of trauma-induced hypercoagulopathy (TIH) due to insensitivity. Lymphatic vessels drain approximately 10% of the interstitial fluid into the lymphatic system and form lymph.SubjectiveThe purpose of this study was to identify the potential lymph biomarkers for TIH.MethodsEighteen male Sprague-Dawley rats were randomly assigned to the sham (non-fractured rats with sham surgery and vehicle treatment), the VEH (fractured rats with vehicle treatment) and the CLO (fractured rats with clopidogrel treatment) group. Thoracic duct lymph was obtained to perform proteomics and untargeted metabolomics.ResultsA total of 1207 proteins and 16,695 metabolites were identified. The top 5 GO terms of lymph proteomics indicated that oxidative stress and innate immunity were closely associated with TIH and antithrombotic therapy. The top 5 GO terms of lymph metabolomics showed that homocystine and lysophosphatidylcholine were the differential expressed metabolites (DEMs) between the sham and VEH groups, while cholic acid, docosahexaenoic acid, N1-Methyl-2-pyridone-5-carboxamide, isoleucine and testosterone are the DEMs between the VEH and CLO group.ConclusionsThis study presents the first proteomic and metabolomic profiling of lymph after TIH and antithrombotic therapy, and predicts the possible lymph biomarkers for TIH.

Influence of Timing of Stenting on Condition of Venous Valves of Lower Extremities, Frequency and Severity of Development of Post-Thrombotic Disease

INTRODUCTION: Acute deep vein thrombosis (DVT) of the lower extremities (LE) is a life-threatening condition, accompanied by high rates of disability among people of working age. Despite early detection of DVT and the use of recommended antithrombotic therapy, damage to the venous wall, development of valvular reflux and post-thrombotic disease (PTD) inevitably occur. The clinical picture of PTD becomes evident after the development of valve incompetence, which leads to vertical venous reflux and chronic venous hypertension. Timely elimination of venous obstruction can preserve the functionality of valve structures, which will subsequently help reduce the frequency and severity of PTD. AIM: To evaluate the impact of the timing of stenting on the condition of the venous valves, the frequency and severity of the development of PTD in patients with acute DVT of LE. MATERIALS AND METHODS: A prospective interventional study included 49 patients with acute iliofemoral thrombosis. After selective thrombolysis, 25 patients underwent early (within 7 days) and 24 patients underwent delayed (7–30 days) stenting. The incidence and severity of PTD was assessed on the Villalta scale at 3, 6 and 12 months. The effect of treatment on the condition of the venous valves of the LE was assessed at 12 months. On ultrasound examination, reflux was assessed using a scoring system. RESULTS: At 12 months, 2 (8%), 13 (52%), and 10 (40%) patients who underwent delayed stenting, developed severe, moderate, or mild PTD, respectively. In the early stenting group, 6 (25%) patients had no symptoms of PTD, 15 (62.5%) and 3 (12.5%) developed mild and moderate PTD, respectively (p = 0.0005). At 12 months, in the early stenting group, the absence of reflux was recorded in 6 (25%) patients, 4 (17%) patients had valve reflux in the femoral segment, and 14 (58%) in the popliteal segment. In the delayed stenting group, valvular incompetence of both segments was detected in 12 (48%) patients; in 4 (16%) and 9 (36%) patients, the valves of the femoral and popliteal veins were preserved; there were no patients without reflux in both segments. Treatment results for this indicator were better if early stenting was performed (p = 0.0005). CONCLUSION: Early stenting after selective thrombolysis in patients with proximal DVT of LE leads to a decrease in the incidence and severity of symptoms of PTD, and can reduce the incidence of reflux in the deep veins.

Embolic Stroke of Undetermined Source: New Data and New Controversies on Cardiac Monitoring and Anticoagulation.

Embolic strokes of undetermined source (ESUS) represent 9%-25% of all ischemic strokes. Based on the suspicion that a large proportion of cardioembolic sources remain undetected among embolic stroke of undetermined source patients, it has been hypothesized that a universal approach of anticoagulation would be better than aspirin for preventing recurrent strokes. However, 4 randomized controlled trials (RCTs), with different degrees of patient selection, failed to confirm this hypothesis. In parallel, several RCTs consistently demonstrated that prolonged cardiac monitoring increased atrial fibrillation detection and anticoagulation initiation compared with usual care in patients with ESUS, and later in individuals with ischemic stroke of known cause (e.g., large or small vessel disease). However, none of these trials or subsequent meta-analyses of all available RCTs have shown a reduction in stroke recurrence associated with the use of prolonged cardiac monitoring. In this article, we review the clinical and research implications of recent RCTs of antithrombotic therapy in patients with ESUS and in high-risk populations with and without stroke, with device-detected asymptomatic atrial fibrillation.

Evaluation of Cardiovascular Risk in People with Type 1 Diabetes: A Comprehensive and Specific Proposed Practical Approach.

People living with type 1 diabetes (T1D) have an increased risk of cardiovascular disease (CVD), and it is the leading cause of morbidity and mortality in this population. CVD risk increases with each uncontrolled risk factor, even in individuals with good glycaemic control. Recommendations for assessing CVD risk in the T1D population are extended from those for type 2 diabetes (T2D) even though the physiopathology and underlying mechanisms of atherosclerosis in T1D are poorly understood and differ from those in T2D. Unlike the assessment of microvascular complications, which is well established in T1D, this is far from being the case for the comorbidities and risk associated with CVD. Aside from classical cardiovascular comorbidities, carotid ultrasound can be useful to stratify CVD risk. The utilization of specific risk scales such as the Steno Type 1 Risk Engine can help to more accurately classify cardiovascular risk in these individuals. The cornerstones of the management of cardiovascular risk in T1D are the promotion of the Mediterranean diet, tight glycaemic control (glycated haemoglobin (HbA1c) < 7%), blood pressure < 130/80mmHg in most patients, and low-density lipoprotein (LDL) cholesterol < 100mg/dL in moderate-risk individuals, < 70mg/dL in high-risk individuals, and < 55mg/dL in very high-risk individuals. Conventional medical follow-up of patients with T1D should be individualized (approximately 2-3 visits per year), and a carotid ultrasound evaluation is recommended every 5 years in the absence of significant preclinical atherosclerosis or more often in those with severe preclinical atherosclerosis. Antithrombotic therapy is recommended in those receiving secondary prevention, those with stenosis > 50% in any arterial bed, and those with an impaired ankle-brachial index. This document is a proposal of a practical approach for the evaluation, classification, and management of CVD risk in individuals living with T1D.

Different antithrombotic strategies after coronary artery bypass grafting to prevent adverse events: a retrospective analysis

ObjectiveCoronary artery bypass grafting (CABG) is associated with antithrombotic therapy in terms of postoperative adverse events; however, it is still unknown whether the early use of such drugs after CABG is safe and effective. In this study, we aim to evaluate the relationship between different postoperative antithrombotic strategies and in-hospital adverse events in patients undergoing isolated coronary artery bypass grafting surgery.MethodsThis was a single-center, retrospective cohort analysis of patients undergoing isolated CABG due to coronary artery disease (CAD) between 2001 and 2012. Data were extracted from the Medical Information Mart for Intensive Care III database. The patients involved were divided into the ASA (aspirin 81 mg per day only) or DAPT (aspirin plus clopidogrel 75 mg per day) group according to the antiplatelet strategy. Patients were also stratified into subgroups based on the type of anticoagulation. The in-hospital risk of bleeding and adverse events was investigated and compared between groups. Propensity score matching (PSM) was performed to reduce the potential effects of a selection bias.ResultsA total of 3274 patients were included in this study, with 2358 in the ASA group and 889 in the DAPT group. Following the PSM, no significant difference was seen in the risk of major bleeding between the two groups according to the PLATO, TIMI or GUSTO criteria. There was no difference in the postoperative mortality. In subgroup analysis, patients given anticoagulant therapy had an increased incidence of bleeding-related events. Multivariable analysis revealed that postoperative anticoagulant therapy and the early use of heparin, but not DAPT, were independent predictors of bleeding-related events.ConclusionsPostoperative DAPT was not associated with an increased occurrence of bleeding-related events in patients undergoing isolated CABG and appears to be a safe antiplatelet therapy. The addition of anticoagulants to antiplatelet therapy increased the risk of bleeding and should be considered cautiously in clinical practice.

460 Exploring Optimal Antithrombotic Strategies for Acute Limb Ischaemia: A Comprehensive Review

Abstract Aim Antithrombotic therapy is an integral part of acute limb ischaemia (ALI) management. This study aimed to systematically review the up-to-date evidence available in antithrombotic management of ALI. Method A systematic search (PubMed, OVID, Embase, and Google Scholar) identifying Randomised Control Trials (RCT) and observational studies following PRISMA guidelines was conducted, to report on outcomes of ALI using different antithrombotic agents. Results 6262 studies were originally screened, after removal of duplicates 10 studies were left that fully matched our criteria. No RCT was found comparing antithrombotic agents’ efficacy. Pre-intervention anticoagulation was associated with a risk reduction of amputation and improved secondary patency in ALI treated with prosthetic bypass grafts. Regarding intra-arterial thrombolysis, a continuous heparin infusion showed no advantage. Low weight molecular heparin should be considered as an alternative to unfractionated heparin in ALI patients after arterial embolectomy. Low dose Rivaroxaban and aspirin are associated with decreased major adverse cardiovascular events and amputation incidence following revascularisation, when compared to aspirin and placebo in ALI. Ticagrelor was not superior to clopidogrel with similar bleeding rates. Conclusions The evidence base is inconclusive to determine a standardised guidance. ALI presentation and aetiology might be the best current guide on the antithrombotic regime choice.

Duration of triple antithrombotic therapy and clinical outcomes after percutaneous coronary intervention in atrial fibrillation

ABSTRACT Background Triple antithrombotic therapy (TAT) with aspirin, a P2Y12 inhibitor, and oral anticoagulation in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) raises concerns about increased bleeding. Regimens incorporating more potent P2Y12 inhibitors over clopidogrel have not been investigated adequately. Research design and methods A retrospective observational study was performed on 387 patients with AF receiving TAT for 1 month (n = 236) or ≤1 week (n = 151) after PCI. Major and clinically relevant non-major bleeding and major adverse cardiac and cerebrovascular events (MACCE) were assessed up to 30 days post-procedure. Results Bleeding was less frequent with ≤1 week versus 1 month of TAT (3.3 vs 9.3%; p = 0.025) while MACCE were similar (4.6 vs 4.7%; p = 0.998). No differences in bleeding or MACCE were observed between ticagrelor/prasugrel and clopidogrel regimens. For patients receiving ≤1 week of TAT, no excess of MACCE was seen in the subgroup given no further aspirin post-PCI compared with those given aspirin for up to 1 week (3.6 vs 5.2%). Conclusions TAT post-PCI for ≤1 week was associated with less bleeding despite greater use of ticagrelor/prasugrel but similar MACCE versus 1-month TAT. These findings support further studies on safety and efficacy of dual therapy with ticagrelor/prasugrel immediately after PCI.

The impact of age, sex, comorbidities, and use of antithrombotics on the clinical course severity among patients surgically treated for urinary bladder tamponade.

To examine the relationship between clinical patient characteristics and the severity of the disease course in patients hospitalized due to urinary bladder tamponade. The severity was assessed based on hemoglobin (Hgb) levels upon admission, the requirement for red blood cell transfusion (RBCT), and length of hospital stay. A retrospective analysis was conducted at a single center, involving 75 patients who were hospitalized due to urinary bladder tamponade. Bladder cancer (33.3%) and postoperative bleeding (28%) were the most common causes of bladder tamponade. Patient age exhibited a negative correlation with Hgb levels upon admission (r = -0.539, P < 0.001) and a positive correlation with the quantity of administered RBCT units (r = 0.425, P < 0.001) and the length of hospitalization (r = 0.541, P < 0.001). The number of comorbidities exhibited a negative correlation with Hgb levels upon admission (r = -0.555, P < 0.001) and a positive correlation with the quantity of administered RBCT units (r = 0.522, P < 0.001) and the length of hospitalization (r = 0.543, P < 0.001). Patients taking antithrombotic therapy (AT) had lower mean Hgb levels on admission (87.8 ± 13.5 g/L vs. 107.6 ± 18.7 g/L, P < 0.001), a higher mean number of administered RBCT units (2.8 ± 2.1 vs. 1.1 ± 1.3, P < 0.001) and longer hospitalizations (4.6 ± 1.6 days vs. 3.1 ± 1.1 days, P < 0.001) compared to those not taking AT. Older patients with multiple comorbidities, particularly those taking AT, should be expected to have a more severe clinical course of bladder tamponade. Therefore, special clinical attention is necessary for this vulnerable patient group.

Contemporary National Incidence and Outcomes of Acute Limb Ischemia

Acute Limb Ischemia (ALI) is a morbid and deadly diagnosis. However, existing epidemiologic studies describing ALI predate the introduction of the Affordable Care Act in 2010 and direct oral anticoagulants in 2011. Thus, we synergized the National Inpatient Sample (NIS) and United States (U.S.) Census to define contemporary trends in the incidence, treatment, and outcomes of ALI in the US. We included emergent admissions of adults with primary diagnosis of lower extremity ALI in survey-weighted NIS data (2005-2020). Mann-Kendal trend test evaluated ALI incidence (primary outcome), anticoagulation usage, insurance coverage, revascularization type, and in-hospital amputation/death. Multivariable logistic regression quantified covariate associations with in-hospital amputation/death. Of 582,322,862 estimated hospitalizations in the NIS, 227,440 met inclusion criteria (mean age 68.80 years, 49.94% women, 76.66% White). ALI incidence peaked in 2006 (7.16/100,000 person-years) but has declined since 2015 to 4.16/100,000 person-years in 2020 (ptrend=.008). Endovascular revascularization, anticoagulation, and Medicaid coverage increased, while self-pay insurance decreased (ptrend<.05). Amputation rates significantly decreased from 8.04% to 6.54% (ptrend=.01) while death rate remained at 5.59% (ptrend=.16) over the study period. Pre-hospitalization anticoagulation was associated with decreased amputation (aOR=0.74 [95%CI 0.65-0.84]) and death (aOR=0.50 [95%CI 0.43-0.57]). When controlling for covariates, women had a higher risk of death (aOR=1.17 [95%CI 1.07-1.27], p<.0001), while Black patients had a higher risk of amputation (aOR=1.24 [95%CI 1.10-1.41], p<.0001). Our U.S. population based epidemiological study demonstrates that ALI incidence and in-hospital amputation rates are decreasing, while mortality remains unchanged. We further highlight the ongoing need for ALI investigation specifically as it relates to access to care, antithrombotic therapy use, treatment strategy, and strategies to combat gender and racial disparities.