Major Bleeding In Patients Research Articles

Abstract 4144581: Diltiazem, Direct Oral Anticoagulants and Risk of Major Bleeding in Patients with Atrial Fibrillation

Background: Existing research suggests a potential increase in bleeding risk associated with the combined use of calcium channel blockers (CCBs) and direct oral anticoagulants (DOACs). However, the evidence remains inconclusive and conflicting. To clarify this relationship, we conducted a meta-analysis to investigate the risk of major bleeding in patients with atrial fibrillation (AF) using diltiazem. Methods: We conducted a comprehensive search of major electronic databases, including PubMed, Embase, and the Cochrane Library, from their inception through April 20, 2024 for relevant studies. The primary endpoint was major bleeding, defined as a composite of bleeding-related hospitalization, requiring blood transfusion, or fatal bleeding. We conducted a conventional meta-analysis using the Hartung-Knapp-Sidik-Jonkman random-effects model. Endpoints are expressed as hazard ratio (HR) and their corresponding confidence intervals (CI). Results: A total of 5 studies with 488,884 patients with AF were included in our study, of which 23.4% of patients were on diltiazem. All patients were also on DOACs. Results of the meta-analysis showed that there was no statistically significant difference between use of diltiazem and the risk of major bleeding (HR 1.16 ; 95% CI 0.94-1.42). Sensitivity analysis showed that this result remained unaltered in terms of magnitude and direction after excluding one study at a time. When stratified by type of control group, both active comparator (HR 1.09 ; 95% CI 0.92-1.30) and non-use subgroups (HR 1.24 ; 95% CI 0.87-1.77) showed that there was no significant difference in the risk of major bleeding with diltiazem use respectively. Conclusion: We observed that there was no significant difference in the risk of major bleeding in diltiazem use compared to controls in AF patients on DOACs. Further large-scale, longitudinal, and prospective studies are essential to validate these findings.

Bleeding Associated With Antiarrhythmic Drugs in Patients With Atrial Fibrillation Using Direct Oral Anticoagulants: A Nationwide Population Cohort Study.

This study investigated drug-drug interactions in patients with atrial fibrillation taking both a direct oral anticoagulant (DOAC) and an antiarrhythmic drug. Using data from the National Health Insurance database (2012-2018), we identified 78 805 patients with atrial fibrillation on DOACs, with 24 142 taking amiodarone, 8631 taking propafenone, 2784 taking dronedarone, 297 taking flecainide, 177 taking sotalol, and 42 772 on DOACs alone. Patients with bradycardia, heart block, heart failure, mitral stenosis, prosthetic valves, or incomplete data were excluded. Propensity score matching compared those taking both DOACs and antiarrhythmic drugs with those on DOACs alone. There was an increased risk of major bleeding in patients concomitantly taking DOACs with amiodarone when compared with matched patients taking DOACs alone (hazard ratio [HR],1.13 [95% CI, 1.04-1.23]; P=0.0044), particularly in patients taking dabigatran (HR, 1.19 [95% CI, 1.03-1.38]; P=0.0175). No significant difference in bleeding risk was found for propafenone, dronedarone, flecainide, or sotalol. The small sample sizes in the flecainide and sotalol groups limit interpretation. Notably, intracranial bleeding risk was higher in patients on DOACs and amiodarone, regardless of age. Additionally, patients <80 years old taking dabigatran with amiodarone or propafenone had a higher risk of gastrointestinal bleeding. Concomitant use of DOACs with amiodarone, but not dronedarone or propafenone, increases the risk of major bleeding, particularly intracranial bleeding. This study provides new evidence to guide clinicians to tailor concomitant anticoagulation and antiarrhythmic therapy for patients with atrial fibrillation.

035. Short-Term Outcomes for Catheter-Directed Thrombolysis for Non-Threatening Acute Limb Ischaemia: A Systematic Review and Meta-Analysis

Background: Acute limb ischemia (ALI) is a rapid reduction in arterial blood flow to a limb, which may jeopardize its viability, particularly in sensory loss or motor impairment. Catheter-directed thrombolysis (CDT) is the preferred treatment in numerous centers for patients with marginally threatening acute limb ischemia (ALI). This meta-analysis examined the short-term effects of catheter-directed thrombolysis (CDT) for patients with non-imminent limb ischemia. Methods: We searched PubMed, ScienceDirect, and the Cochrane Library to locate observational papers and trials published from 2014 up to early 2024 that report on the outcomes of CDT in patients with ALI. The outcome of this study was mortality rate, amputation rate, and major bleeding. We utilized R Studio to perform the meta-analysis. Results: Nine trials were included, involving 1,067 patients receiving CDT for non-imminent acute limb ischemia. Our results indicate that the pooled mean short-term amputation rate was 10% (95% CI [0.06; 0.15], p &lt; 0.01), the major bleeding rate was 5% (95% CI [0.00; 0.09], p = 0.03), and the short-term death rate was 4% (95% CI [0.03; 0.06], p = 0.08). Our findings indicate a low incidence of short-term death, amputation, and major bleeding in patients undergoing CDT. Conclusion: This meta-analysis reveals a low incidence of short-term mortality, amputation, and major bleeding in patients undergoing Catheter-directed thrombolysis. Further investigations are necessary to determine if CDT should be utilized for the revascularization of limbs with non-urgent ischemia.

Application of DOAC Score for the risk-stratification of major bleeding in patients with venous thromboembolism on direct oral anticoagulants: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction Bleeding complications are still a major concern in anticoagulation therapy for venous thromboembolism (VTE), even in the direct oral anticoagulant (DOAC) era. Thus, the risk stratification of bleeding during anticoagulation therapy is essential, although most of currently available bleeding risk scores have been developed from patients receiving vitamin K antagonists, which could have limited validity in those receiving DOACs. Very recently, the DOAC Score has been developed to predict major bleeding in patients with atrial fibrillation on DOACs; however, the score has not yet been validated in patients with VTE. Purpose The present study aimed to evaluate the usefulness of the DOAC Score in patients with VTE, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The present study population was consisted of 3539 patients with VTE who received DOACs and had a calculated DOAC Score. The eligible patients were classified into 5 risk categories: very low (score 0–3), low (score 4–5), moderate (6–7), high (score 8–9), and very high (score ≥10). We used the Kaplan-Meier method to estimate the cumulative incidence and assessed the discriminatory ability of the DOAC Score for major bleeding at 1 year by calculating the area under the receiver operating characteristic curve. We also assessed the discriminatory ability of the VTE-BLEED and RIETE scores. Results In the present study population, the very low-risk group accounted for 1437 patients (41%), low-risk group for 828 (23%), moderate-risk group for 812 (23%), high-risk group for 326 (9.2%), and very high-risk group for 136 (3.8%). The proportion of anemia was highest in the very high-risk group (71%) and lowest in the very low-risk group (47%). The prevalence of active cancer was highest in the low-risk group (36%) and lowest in the very high-risk group (18%). During the first year of anticoagulation therapy, major bleeding occurred in 180 patients. The cumulative 1-year incidence of major bleeding seemed to be different according to the 5 groups, but the risks could not be well-stratified (Figure 1). The discriminating power of the DOAC Score was relatively low with a C-statistic of 0.52 (95% CI, 0.48–0.57) (Figure 2), while those of VTE-BLEED and RIETE scores were modest with C-statistics of 0.66 (95% CI, 0.60–0.73) and 0.67 (95% CI, 0.64–0.71), respectively. Conclusions The risk of 1-year major bleeding on DOACs in patients with VTE was not well-stratified according to the risk categories by the DOAC Score, which might suggest that patients with VTE have different risk factors for bleeding on DOACs as compared to those with atrial fibrillation. A new bleeding risk score for DOAC specifically in patients with VTE would be warranted in the future.Figure 1Figure 2

Comparison of 600 mg VS 300 mg clopidogrel loading dose for patients with ischemic heart disease: a meta-analysis of randomized controlled trials

Abstract Background While a 600-mg loading dose (LD) of clopidogrel has demonstrated superior inhibition of platelet function compared to 300-mg LD, the clinical evidence supporting this superiority is limited. The debate centers on whether a higher clopidogrel LD regimen in primary percutaneous coronary intervention outperforms the standard 300 mg LD, with potential benefits being more pronounced in higher-risk patients. Balancing enhanced platelet inhibition to reduce ischemic events against the associated risk of increased bleeding remains a critical consideration in determining the optimal loading dose of clopidogrel for patients with ischemic heart disease. Purpose The objective of this meta-analysis is to validate current randomized trials that investigate the efficacy and safety of two clopidogrel loading regimens (600 mg vs 300 mg) in patients with ischemic heart disease treated with primary percutaneous coronary intervention. Method A systematic literature search for randomized controlled trials was performed comparing 600 mg with 300 mg LD of clopidogrel using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov. and Herdin PH. Studies included those between 2010 - 2023 involving human subjects. The primary efficacy endpoint was a 1-month rate of major adverse cardiac event (MACE) and the primary safety outcome was bleeding adverse effects. Result Nine randomized control studies involving 29,827 patients were included in the efficacy analysis. Mean duration of follow-up was 30 days. Only 8 studies were eligible for safety analysis. Compared with standard LD clopidogrel, high LD significantly reduced incidence of overall MACE (OR:0.82, 95% CI:0.74-0.91, p=0.0002), nonfatal myocardial infarction (OR:0.56; 95% CI:0.32-0.99, p = 0.15) and target vessel revascularization (OR 0.63; 95% CI 0.41 to 0.95, p = 0.03 ), without significant difference in terms of cardiac death (OR:0.89; 95% CI:0.76-1.04, p=0.15) and stroke (OR 0.92; 95% CI 0.67 to 1.26, p = 0.61). However, major bleeding risk was higher in the 600 mg LD (1.9%; 261/13288) compared with 300 mg LD (2.4%; 328/13242) [OR:1.27; 95% CI:1.08-1.49, p=0.005] without significant difference in minor bleeding (OR:1.05; 95% CI:0.94-1.17, p=0.35). Conclusion The administration of 600 mg of clopidogrel LD reduces the overall risk of MACE with an associated increased risk of major bleeding in patients with ischemic heart disease undergoing primary percutaneous coronary intervention.MACE OUTCOMES

The incidence of death and risk factors for mortality following major bleeding in patients anticoagulated with factor Xa inhibitors: an observational study in the UK clinical setting (AXIOM UK)

Abstract Background Major bleeding (MB) in association with anticoagulant use results in significant mortality. Mortality can be directly attributed to bleeding, or may follow bleeding complications such acute kidney injury, myocardial infarction, stroke and other cardiovascular events. Most real-world data relating to bleeding mortality is derived from cohorts receiving vitamin-K antagonists. We investigated all-cause mortality (ACM) after MB in a large cohort anticoagulated with Factor Xa inhibitors (FXai), e.g. direct oral anticoagulants (DOAC) rivaroxaban, apixaban and low-molecular-weight heparins (LMWH). Purpose To describe incidence rates of and risk factors for ACM following MB in patients receiving FXai. To investigate MB related ACM by bleeding site, treatment indication, treatment subgroups and individual and cumulative time periods. Methods Retrospective cohort analysis of new users of FXai, between 2012-2020, for therapeutic indications including atrial fibrillation (AF), venous thromboembolism, bioprosthetic cardiac valves or adult congenital heart disease was conducted. MB was defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. Incidence rates were reported per 100 person-years. Sub-distribution hazard ratios with 95% confidence intervals (95% CI) were estimated from Fine and Gray regression models accounting for competing risks. Results In 240,357 new users of FXai, 88% used an oral FXai. The most common FXai indication was AF (72%). There were 10,163 patients (4.2%) hospitalised for bleeding events during FXai use. Of these, 3,873 MB events (38%) fulfilled the ISTH definition of MB and 1312 died during 3,542 person years of follow-up (Table 1). ACM incidence rates varied by time, indication, bleeding subtype, and drug type. ACM occurred in 926 patients (23.9%) in the first month. Mortality rates were highest in the first month 607 (95% CI 568-647) per 100 person years, the rates then decreased over the year but remained elevated throughout the first year compared with subsequent years. Those receiving LMWH had higher ACM than those receiving a DOAC, but this was not significant in the adjusted risk factor analysis. Risk factors for ACM following bleeding included age ≥80, and a history of current smoking, myocardial infarction, congestive heart failure, peripheral artery disease, Stage 4 or 5 kidney disease, metastatic cancer, and intracranial haemorrhage. Age&amp;lt;60, bleeding following major trauma, and a history of anaemia were associated with lower risk of ACM (Table 2). Conclusions There is a significant incidence of ACM following MB among FXai users. The incidence rate of ACM in patients treated with FXai was highest in the first month after FXai initiation, declined during the first year and then plateaued. Multiple risk factors associated with ACM have been recognised and these could guide urgent therapies such as antidotes.

Oral anticoagulants or antiplatelets for cryptogenic stroke: a systematic review and meta-analysis

Abstract Background Cryptogenic strokes comprise 20 to 30% of ischemic strokes and include a substantial proportion classified as embolic stroke of undetermined source (ESUS). However, the optimal antithrombotic strategy for cryptogenic stroke remains contentious. Purpose We conducted a systematic review and meta-analysis to compare the efficacy and safety of oral anticoagulants (OAC) versus antiplatelets in patients with cryptogenic stroke. Methods Six electronic databases of PubMed, Embase, Web of Science, the Cochrane Library, Google Scholar and ClinicalTrials.gov were searched from inception to Feb 15, 2024 to identify relevant randomized controlled trials (RCTs) comparing stroke recurrence and major bleeding rates between OAC and antiplatelets in cryptogenic stroke patients. We included trials adhering to a stringent diagnostic work-up for cryptogenic stroke, defined as cerebral infarction not attributed to definite sources of cardioembolism, large artery atherosclerosis, or small artery disease despite undergoing comprehensive investigations. The primary outcome was recurrent ischemic stroke, and the secondary outcome was major bleeding based on International Society of Thrombosis and Hemostasis criteria. Subgroup analysis was conducted for ESUS patients with an increased risk of cardiac emboli, such as patent foramen ovale (PFO) and atrial cardiopathy, defined as lead V1 terminal P-wave &amp;gt; 5000 μV × ms in electrocardiogram, serum N-terminal pro-B-type natriuretic peptide level &amp;gt; 250 pg/mL, and left atrial diameter (LAE) &amp;gt; 4 cm, or LAE index ≥ 3 cm/m2 on echocardiogram. Hazard ratio (HR) with 95% confidence (CI) was used as a measure of the effect estimates for aforementioned outcomes. Random-effects meta-analysis was performed using a restricted maximum likelihood model given between-study variance is inevitable. Results Our meta-analysis included 9 RCTs with a total of 15,139 patients (OAC = 7,343; antiplatelets = 7,796). ARCADIA, RE-SPECT ESUS, and NAVIGATE ESUS Trial investigated apixaban, dabigatran, and rivaroxaban, respectively, while warfarin was primarily used as OAC in the remaining six trials. Aspirin was predominantly utilized for antiplatelet therapy. There was no significant difference in recurrent ischemic stroke between OAC and antiplatelets (HR, 0.90; 95% CI, 0.78 to 1.04; I2 = 0%). However, OAC use was associated with a significantly higher risk of major bleeding (HR, 1.66; 95% CI, 1.07 to 2.56; I2 = 36%). Subgroup analysis in ESUS patients revealed comparable rates of recurrent ischemic stroke in those with atrial cardiopathy (HR, 0.91; 95% CI, 0.65 to 1.29; I2 = 0%) and PFO (HR, 0.72; 95% CI, 0.49 to 1.07; I2 = 0%). Conclusions Our meta-analysis suggests that OAC use does not decrease the risk of recurrent ischemic stroke compared with antiplatelet use but is associated with a significantly higher risk of major bleeding in patients with cryptogenic stroke.Primary (A) and secondary (B) outcomesSubgroup analysis for recurrent stroke

Antithrombotic strategies after cryptogenic stroke: a systematic review, pairwise, and network meta-analysis of randomized controlled trials

Abstract Background No definite etiology is identified in 30-40% of ischemic stroke cases, which is known as cryptogenic stroke. Several antithrombotic strategies have been investigated for cryptogenic stroke management; however, the optimal strategy remains unknown. Purpose We aim to assess the efficacy and safety of oral anticoagulants (OACs) versus aspirin, and the comparative efficacy and safety of different OACs after cryptogenic stroke. Methods A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until February 2024. We used the fixed-effects model to report dichotomous outcomes using a risk ratio (RR), with a 95% confidence interval (CI). Analysis was conducted using R, version 4.2.0. Results Seven RCTs with 15.240 patients were included. In pairwise analysis, there was no difference between OACs and aspirin regarding all-cause mortality (RR: 1.13, CI [0.89, 1.43], P= 0.33) and stroke recurrence (RR: 0.93, CI [0.82, 1.07], P= 0.31). However, OACs were associated with a significantly increased incidence of major bleeding (RR: 1.6, CI [1.24, 2.05], P= 0.01), with no difference regarding the incidence of intracranial hemorrhage (RR: 1.09, CI [0.3, 3.97], P= 0.9). Moreover, in network analysis, none of the OACs showed a significant efficacy in preventing all-cause mortality and stroke recurrence compared to aspirin. However, only rivaroxaban significantly increased the incidence of major bleeding (RR: 2.69, CI [1.67, 4.33]). Conclusion OACs did not protect against stroke recurrence or decrease the incidence of all-cause mortality but increased the incidence of major bleeding in patients with cryptogenic stroke.

Bleeding and Thrombotic Events in Hemodialysis Patients with Atrial Fibrillation on Anticoagulation and Antiplatelet Therapy: A 24-Month Cohort Study

Background and Objectives: Patients undergoing chronic hemodialysis (HD) are predisposed to both thrombotic and bleeding complications due to the complex interplay of end-stage renal disease (ESRD), cardiovascular comorbidities, and the routine use of anticoagulant and antiplatelet therapies. This study aimed to investigate the incidence of bleeding and thrombotic events in chronic HD patients receiving anticoagulant and antiplatelet therapy, with a specific focus on those with atrial fibrillation (AF). Materials and Methods: A total of 224 patients, with 43 (19%) of them diagnosed with AF, were included in this single-center, observational cohort study conducted over 24 months. The cohort was divided into three groups: patients without anticoagulation, those on warfarin monotherapy, and those on combined warfarin and aspirin therapy. Bleeding events were classified as major, clinically relevant non-major bleeding (CRNMB), or minor bleeding, while thrombotic events included ischemic stroke, myocardial infarction, pulmonary embolism, and arteriovenous fistula thrombosis. Results: Overall, 35.7% of patients experienced a bleeding event, with major bleeding occurring in 9.4%. Patients with AF had significantly higher rates of major bleeding (18.6%) compared to those without AF (7.18%; p = 0.043), especially in the combined therapy group. Mortality due to bleeding was also higher in AF patients (14%). In contrast, thrombotic events occurred in 26.8% of patients, with AF patients experiencing significantly more events (48.8%) compared to non-AF patients (21.5%; p = 0.0006). The hazard ratio (HR) for major bleeding in patients on combined warfarin and aspirin therapy was 2.56 (p = 0.016), while the HR for thrombotic events was 2.34 (p = 0.0202). Conclusions: These findings highlight the increased risks of both bleeding and thrombosis in chronic HD patients with AF, particularly those on combined anticoagulation and antiplatelet therapy.

Predictors of recurrent venous thromboembolism and major bleeding in patients with cancer: A secondary analysis of the CANVAS trial

IntroductionPatients with cancer have an increased risk of developing venous thromboembolism (VTE) but also have an increased risk of both recurrent VTE and bleeding with anticoagulation compared to anticoagulated patients without cancer. CANVAS, a randomized pragmatic effectiveness trial, compared the direct oral anticoagulants a class to low molecular weight heparin for treatment of a new VTE in patients with cancer. The aim of this prespecified secondary analysis of the CANVAS trial is to identify predictors of both recurrent VTE and major bleeding in patients with cancer and new VTE. MethodsData from the 671 participants in the analysis population were used to identify predictors of recurrent VTE and bleeding during the 6-month treatment period. Significant predictors identified in the univariable models were carried forward in the multivariable models to identify independent predictors of both risks. ResultsIndependent predictors of recurrent VTE include ECOG performance status ≥2 (HR, 3.19 [95 % CI, 1.45–7.02]; P < .005), presence of metastatic disease (HR, 2.57 [95 % CI, 1.14–5.80]; P = .023), treatment with bevacizumab (HR, 2.50 [95 % CI, 1.04–5.99]; P = .041), and deep vein thrombosis without pulmonary embolus as index VTE (HR, 1.86 [95 % CI, 1.04–3.33]; P = .037). Independent predictors of major bleeding include serum albumin <3.5 g/dL (HR 1.97 [95 % CI, 1.02–3.79]; P = .044) and metastatic disease (HR 2.80 [95 % CI, 1.08–7.22]; P = .034). ConclusionFindings from this pre-specified analysis of the CANVAS trial identified risk factors for recurrent VTE and major bleeding in a population of participants with cancer and new VTE that reflect current oncology clinical practice. Results can be used to identify at risk patients in practice and inform new risk prediction models to improve the care of these patients.

Transfer RNAs are Linked to Ischemic Stroke and Major Bleeding in Patients with End-Stage Kidney Disease.

Patients with end-stage kidney disease (ESKD) are at very high risk for thromboembolism and bleeding. This study aimed to identify small noncoding RNAs (sncRNAs), specifically microRNAs and transfer-RNA (tRNA)-derived fragments (tRFs), as potential novel biomarkers for predicting thromboembolism and bleeding in this high-risk population. In this sncRNA discovery research, we leveraged the VIVALDI cohort, consisting of 625 ESKD patients on hemodialysis, to conduct two nested case-control studies, each comprising 18 participants. The primary outcomes were ischemic stroke in the first study and major bleeding in the second. Plasma samples were processed using the miND pipeline for RNA-seq analysis to investigate differential expression of microRNAs and tRNA/tRFs between cases and their respective matched controls, with results stringently adjusted for the false discovery rate (FDR). No significant differential expression of microRNAs for either ischemic stroke or major bleeding outcomes was observed in the two nested case-control studies. However, we identified four tRNAs significantly differentially expressed in ischemic stroke cases and seven in major bleeding cases, compared with controls (FDR < 0.1). Coverage plots indicated that specific tRNA fragments (tRFs), rather than full-length tRNAs, were detected, however. Alternative mapping approaches revealed challenges and technical limitations that precluded in-depth differential expression analyses on these specific tRFs. Yet, they also underscored the potential of tRNAs and tRFs as markers for thromboembolism and bleeding. While microRNAs did not show significant differential expression, our study identifies specific tRNAs/tRFs as potential novel biomarkers for ischemic stroke and major bleeding in ESKD patients.

Prognosis of major bleeding based on residual variables and machine learning for critical patients with upper gastrointestinal bleeding: A multicenter study

BackgroundUpper gastrointestinal bleeding (UGIB) is a significant cause of morbidity and mortality worldwide. This study investigates the use of residual variables and machine learning (ML) models for predicting major bleeding in patients with severe UGIB after their first intensive care unit (ICU) admission. MethodsThe Medical Information Mart for Intensive Care IV and eICU databases were used. Conventional ML and long short-term memory models were constructed using pre-ICU and ICU admission day data to predict the recurrence of major gastrointestinal bleeding. In the models, residual data were utilized by subtracting the normal range from the test result. The models included eight algorithms. Shapley additive explanations and saliency maps were used for feature interpretability. ResultsTwenty-five ML models were developed using data from 2604 patients. The light gradient-boosting machine algorithm model using pre-ICU admission residual data outperformed other models that used test results directly, with an AUC of 0.96. The key factors included aspartate aminotransferase, blood urea nitrogen, albumin, length of ICU admission, and respiratory rate. ConclusionsML models using residuals improved the accuracy and interpretability in predicting major bleeding during ICU admission in patients with UGIB. These interpretable features may facilitate the early identification and management of high-risk patients, thereby improving hemodynamic stability and outcomes.

A multicenter study of the risk of major bleeding in patients with and without cirrhosis undergoing percutaneous liver procedures.

Percutaneous liver procedures are frequently performed in patients with abnormal coagulation tests. Current guidelines suggest prophylactic transfusion is not mandatory in all patients with liver disease or cirrhosis, depending on the risk of bleeding. This study aims to describe the incidence and risk of major bleeding after percutaneous liver procedure in patients with and without cirrhosis. This retrospective study includes patients who underwent percutaneous liver biopsy and radiofrequency and microwave ablation of liver lesions at 3 centers in Spain. A transfusion protocol was considered for platelet counts <50,000 and/or international normalized ratio >1.5. The primary outcome was major bleeding. A total of 1797 patients were included in the study, with 316 having cirrhosis (18%) and 1481 without cirrhosis (82%). Among the patients with cirrhosis, 80 were classified as Child A, and percutaneous liver biopsy was the most frequent procedure (86%). Fourteen patients (0.8%) experienced major bleeding, with 0.4% occurring in radiofrequency and microwave ablation and 0.8% in percutaneous liver biopsy. Bleeding occurred in 0.6% of patients with cirrhosis compared to 0.8% in those without ( p = ns). No clinical or procedural variables were associated with bleeding. Twenty-five patients (1.4%) had an international normalized ratio >1.5, and 22 patients (1.2%) had a platelet count <50,000. Only 24% (6/25) of patients with an international normalized ratio >1.5 were transfused with fresh frozen plasma, and 72% (16/22) of those with platelet counts <50,000 received platelet transfusion. Patients with cirrhosis were more frequently transfused (5.9% vs. 1.5%). None of the patients who met the criteria for transfusion experienced major bleeding, regardless of whether they received a transfusion, and none of the patients who had a major bleeding episode met the transfusion criteria. In this cohort, major bleeding after percutaneous liver procedure occurred in <1% of patients, making it a low-risk procedure for patients with and without cirrhosis. Although not uniformly adopted, the current transfusion protocol still led to unnecessary blood product administration.

Comparative analysis of COVID-19-associated venous thromboembolism outcomes: evolution from 2020 to 2021-2022.

Patients with COVID-19 are at an increased risk for venous thromboembolism (VTE). With the advent of vaccinations and novel treatments from 2020 through 2022, the landscape of COVID-19 has evolved. Notably, the effects of such interventions on the outcomes of COVID-19-associated VTE have not been thoroughly examined. Data from the RIETE registry were analyzed to evaluate 90-day VTE-related outcomes (all-cause mortality, major bleeding, and VTE recurrences) in patients with COVID-19-associated VTE. We compared the periods before and after the widespread introduction of COVID-19 vaccines: March to December 2020 (pre-vaccine period) and March 2021 to December 2022 (post-vaccine period). Statistical analysis included mixed-effects parametric survival-time models. Among 1,620 patients with COVID-19-associated VTE, most (74.1%) were identified during 2020 period. The analysis revealed a more than two-fold increase in the risk of death within 90days (adjusted hazard ratio [HR]: 2.27; 95% confidence interval, CI: 1.18-4.38) and major bleeding (adjusted HR: 2.91; 95%CI: 1.08-7.84) for patients from the 2020 period compared to those from the 2021-2022 period. Inpatient subgroup analysis confirmed the observed mortality differences. The frequency of recurrent VTE was low (1.1 vs. 0.7%, respectively), and did not show significant variation between the two periods. Our research provides a comparative perspective on the clinical outcomes of COVID-19-associated VTE before and after the introduction of vaccines. Our findings reveal a significant decrease in the incidence of 90-day mortality and major bleeding in patients with COVID-19-associated VTE in the 2021-2022 period.

Risk factors for major bleeding in patients with atrial fibrillation and CKD G3-G5D on oral anticoagulants.

Patients with chronic kidney disease (CKD) and atrial fibrillation (AF) on oral anticoagulants (OACs) are at high risk of bleeding. Determinants of major bleeding risk in OAC users with AF and CKD are not well established and available bleeding score systems do not perform well in CKD. This study aims to present risk factors associated with major bleeding in a Swedish cohort of OAC-treated patients with CKD G3-5D. We conducted a Swedish register-based cohort study including patients with AF and CKD G3-5D on warfarin or direct OACs (DOACs) between 2009 and 2018. Data were collected from high-quality registers including the Swedish Renal Registry and Auricula, a register for AF and OACs. Risk factors for major bleeding were investigated with Cox regression analysis. Of 2453 included patients, 59% were on warfarin (time in therapeutic range 67%) and 41% on DOACs. Major bleeding rates were 8.9/100 patient-years. Factors associated with increased bleeding risk were glomerular filtration rate category, G5/5D versus G3 {hazard ratio [HR] 1.92 [95% confidence interval (CI) 1.43-2.56]}, previous gastrointestinal bleeding [HR 1.77 (95% CI 1.39-2.25)], previous other bleeding [HR 1.33 (95% CI 1.09-1.62)], congestive heart failure [HR 1.36 (95% CI 1.11-1.68)], male sex [HR 1.28 (95% CI 1.03-1.60)] and vascular disease [HR 1.35 (95% CI 1.01-1.79)]. Patients with AF and G3-5D on OACs are at a high risk of bleeding. Previous major bleeding and kidney failure are strongly associated with major bleeding. The present study also shows an association between OAC-associated bleeding and male sex, congestive heart failure and vascular disease. Knowledge about determinants of bleeding in advanced CKD is essential when deciding on when to anticoagulate or not.

External validation of the Pulmonary Embolism-Syncope, Anemia, and Renal Dysfunction bleeding score for early major bleeding in patients with acute pulmonary embolism: from the COMMAND VTE Registry-2

BackgroundThere is no established risk score for anticoagulant-related bleeding during the acute phase in patients with pulmonary embolism (PE). The PE-Syncope, Anemia, and Renal Dysfunction (PE-SARD) bleeding score was developed to predict early major bleeding but has not yet been fully externally validated. ObjectivesTo externally validate the PE-SARD bleeding score. MethodsUsing the COntemporary ManageMent AND outcomes in patients with Venous ThromboEmbolism (COMMAND VTE) Registry-2 database, which enrolled 5197 consecutive acute symptomatic venous thromboembolism patients among 31 centers in Japan between January 2015 and August 2020, we identified acute PE patients. We divided them into 3 groups by the score: high-risk (>2.5 points), intermediate-risk (1-2.5 points), and low-risk (0 points). The discriminating and calibration performances of the score for 30-day major bleeding were assessed. Subgroup analyses based on active cancer were also performed. ResultsOf 2781 eligible patients, the high-risk group accounted for 557 patients (20%), intermediate-risk group for 1412 (51%), and low-risk group for 812 (29%). Major bleeding occurred in 121 patients within 30 days. The cumulative 30-day incidence of major bleeding substantially increased in the higher risk categories by the score (high-risk group, 8.2% [95% CI, 5.9%-10.5%]; intermediate-risk group, 4.6% [95% CI, 3.5%-5.7%]; and low-risk group, 1.8% [95% CI, 0.8%-2.7%]). The discriminating power of the score was modest with a C statistic of 0.65 (95% CI, 0.61-0.70), with a good calibration performance with a score of <4 points, except for that in active cancer patients. ConclusionThe PE-SARD bleeding score had a modest discriminating performance with a limited calibration performance in acute PE patients without active cancer.

Diltiazem, direct oral anticoagulants, and risk of major bleeding in patients with atrial fibrillation

Diltiazem, direct oral anticoagulants, and risk of major bleeding in patients with atrial fibrillation

#430 Risk factors for major bleeding in patients with non-valvular atrial fibrillation and CKD G3-G5D on oral anticoagulants

Abstract Background and Aims We previously published a register-based cohort study comparing direct oral anticoagulants (DOAC) and warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) GFR category 3-5 (G3-G5) including patients on dialysis (G5D) (1). This study showed that DOAC was associated with lower risk of major bleeding but similar risk of ischemic stroke compared to warfarin. Bleedings were however more common than strokes, especially in advanced CKD (G5-G5D) where the risk of major bleeding was up to 10 times higher than the risk of stroke. Subsequently, the stroke- and bleeding risk in patients with AF and advanced CKD must be carefully evaluated when deciding on whether to prescribe oral anticoagulants (OAC) or not. Available stroke- and bleeding scoring systems do not perform well in CKD (2, 3). This study aims to present risk factors associated with major bleeding in a Swedish cohort of OAC-treated patients with CKD G3-G5D. Method Data was collected from high quality Swedish healthcare registers including Swedish Renal Registry and Auricula, a register for atrial fibrillation and oral anticoagulants and the National Patient Register. Patients with eGFR&amp;lt;60 ml/min/1.73m2 and non-valvular atrial fibrillation and either DOAC (apixaban, rivaroxaban, edoxaban and dabigatran) or warfarin treatment between 2009-2018 where included. DOAC treatment periods were collected from the Swedish Prescribed Drug Register (PDR), starting from dispense date covering assumed standard pill use and an additional 30 days grace period. Warfarin treatment periods were collected directly from Auricula. An undefined treatment was a period of no OAC or a period of warfarin from PDR not matching a treatment period in Auricula. All periods of OAC treatment with either DOAC or warfarin were evaluated in a multivariate Cox regression model regarding the risk of major bleeding requiring inpatient care. Time-dependent covariates adjusted for in the model were age, sex, years from study start, GFR category, congestive heart failure, diabetes mellitus, hypertension, excessive alcohol use, liver disease, vascular disease, previous gastrointestinal bleeding, intracranial bleeding, other bleeding, ischemic stroke/ transient ischemic attack (TIA), myocardial infarction, PCI and exposures (DOAC, warfarin and periods of undefined treatment). Results Of 2453 included patients, 59% had warfarin (time in therapeutic range, TTR, 67%) and 41% DOAC at inclusion, predominantly apixaban (81% of DOAC users). The mean age was 77 years, 28.3% had G3, 45.4% G4, 9.1% G5 and 17.3% G5D (Table 1). Mean follow up was 2.2 years. During follow up 424 major bleedings occurred yielding 8.9 (95% confidence interval 8.1-9.8) bleedings per 100 patient-years. Table 2 shows effect estimates of each covariate on the outcome major bleeding. Covariates, besides warfarin, associated with increased risk of major bleeding were GFR category, G5/5D versus G3, hazard ratio 1.92 (95% CI 1.43-2.56), previous GI bleeding, 1.77 (1.39-2.25) and previous other bleeding 1.33 (1.09-1.62). Other factors associated with major bleeding were congestive heart failure 1.36 (1.11-1.68), male sex 1.28 (1.03-1.60) and vascular disease, 1.35 (1.01-1.79). Conclusion Patients with non-valvular atrial fibrillation and CKD G3-G5D on OAC are at high risk of major bleeding. Previous major bleeding and kidney failure are strongly associated with major bleeding, this reiterates the results of many previous studies. The present study also shows an association between OAC-associated major bleeding in CKD and male sex, congestive heart failure and vascular disease. Similar associations have been showed in non-CKD cohorts previously but is inadequately studied in CKD. Knowledge about risk factors for major bleeding on OAC in advanced CKD is essential when deciding on when to anticoagulate or not.

Apixaban vs Aspirin According to CHA2DS2-VASc Score in Subclinical Atrial Fibrillation: Insights From ARTESiA

BackgroundARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation) demonstrated that apixaban, compared with aspirin, significantly reduced stroke and systemic embolism (SE) but increased major bleeding in patients with subclinical atrial fibrillation. ObjectivesTo help inform decision making, the authors evaluated the efficacy and safety of apixaban according to baseline CHA2DS2-VASc score. MethodsWe performed a subgroup analysis according to baseline CHA2DS2-VASc score and assessed both the relative and absolute differences in stroke/SE and major bleeding. ResultsBaseline CHA2DS2-VASc scores were <4 in 1,578 (39.4%) patients, 4 in 1,349 (33.6%), and >4 in 1,085 (27.0%). For patients with CHA2DS2-VASc >4, the rate of stroke was 0.98%/year with apixaban and 2.25%/year with aspirin; compared with aspirin, apixaban prevented 1.28 (95% CI: 0.43-2.12) strokes/SE per 100 patient-years and caused 0.68 (95% CI: −0.23 to 1.57) major bleeds. For CHA2DS2-VASc <4, the stroke/SE rate was 0.85%/year with apixaban and 0.97%/year with aspirin. Apixaban prevented 0.12 (95% CI: −0.38 to 0.62) strokes/SE per 100 patient-years and caused 0.33 (95% CI: −0.27 to 0.92) major bleeds. For patients with CHA2DS2-VASc =4, apixaban prevented 0.32 (95% CI: −0.16 to 0.79) strokes/SE per 100 patient-years and caused 0.28 (95% CI: −0.30 to 0.86) major bleeds. ConclusionsOne in 4 patients in ARTESiA with subclinical atrial fibrillation had a CHA2DS2-VASc score >4 and a stroke/SE risk of 2.2% per year. For these patients, the benefits of treatment with apixaban in preventing stroke/SE are greater than the risks. The opposite is true for patients with CHA2DS2-VASc score <4. A substantial intermediate group (CHA2DS2-VASc =4) exists in which patient preferences will inform treatment decisions. (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; NCT01938248)

Association of Age- and Body Mass Index-Stratified High On-Treatment Platelet Reactivity With Coronary Intervention Outcomes in East Asian Patients.

Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on-treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (<67 years of age or ≥67 years of age) and BMI (≤22.6 kg/m2 or >22.6 kg/m2). Patients <67 years of age with HPR had increases in both MACCEs (adjusted hazard ratio [HR], 1.436 [95% CI, 1.106-1.867]; P=0.007) and major bleeding (adjusted HR, 1.584 [95% CI, 1.095-2.290]; P=0.015) compared with the those with non-HPR, respectively. In patients ≥67 years of age with HPR, there were no differences in MACCEs, but there was a decrease in major bleeding (adjusted HR, 0.721 [95% CI, 0.542-0.959]; P=0.024). Meanwhile, patients with HPR with BMI >22.6 kg/m2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140-1.688]; P=0.001). No differences were shown in major bleeding. HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.