Difference In Risk Of Bleeding Research Articles

Transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec gene therapy: A simulation study for individuals with severe haemophilia A.

Valoctocogene roxaparvovec, a gene therapy evaluated in the phase 3 GENEr8-1 trial, supports endogenous factor VIII (FVIII) production to prevent bleeding in people with severe haemophilia A. Individuals receiving emicizumab, an antibody mimicking the function of activated FVIII, were excluded from GENEr8-1 enrolment since emicizumab was an investigational therapy at the time of trial initiation. Utilize pharmacokinetic simulations to provide guidance on best practices for maintaining haemostatic control while transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec. To estimate bleeding risk at weekly intervals following valoctocogene roxaparvovec infusion, a published emicizumab pharmacokinetic model was used to simulate emicizumab concentrations and merged with FVIII activity time-course data for participants in GENEr8-1. The analysis investigated three approved emicizumab dosing regimens for two transition scenarios that varied whether the last dose of emicizumab was administered on the same day or 4weeks after valoctocogene roxaparvovec infusion. Simulations demonstrated administering the last emicizumab dose the day of valoctocogene roxaparvovec infusion and 4weeks after offered similar levels of haemostatic control, and bleeding risk was similar for all emicizumab dosing regimens. An algorithm was developed to provide guidance for discontinuation of emicizumab. Theoretical cases based on GENEr8-1 participants are presented to illustrate how decisions may vary among individuals. Pharmacokinetic simulations demonstrated no clinically meaningful difference in bleeding risk caused by decaying emicizumab levels and rising gene therapy-derived endogenous FVIII for all examined emicizumab doses and dosing regimens. Therefore, multiple approaches can safely transition individuals from emicizumab prophylaxis to valoctocogene roxaparvovec.

Sex Differences in Bleeding Risk Associated With Antithrombotic Therapy Following Percutaneous Coronary Intervention.

Background: Antithrombotic therapy is crucial for secondary prevention of cardiovascular disease (CVD), but women with CVD may face increased bleeding complications post-percutaneous coronary intervention (PCI) under antithrombotic therapy. However, women are often underrepresented in clinical trials in this field, so evidence for sex-specific recommendations is lacking. Methods and Results: A search on PubMed was conducted for English-language articles addressing bleeding complications and antithrombotic therapy in women. Despite women potentially showing higher baseline platelet responsiveness than men, the clinical implications remain unclear. Concerning antiplatelet therapy post-PCI, although women have an elevated bleeding risk in the acute phase, no sex differences were observed in the chronic phase. However, women require specific considerations for factors such as age, renal function, and weight when determining the dose and duration of antiplatelet therapy. Regarding anticoagulation post-PCI, direct oral anticoagulants may pose a lower bleeding risk in women compared with warfarin. Concerning triple antithrombotic therapy (TAT) post-PCI for patients with atrial fibrillation, there is a lack of evidence on whether sex differences should be considered in the duration and regimen of TAT. Conclusions: Recent findings on sex differences in post-PCI bleeding complications did not provide enough evidence to recommend specific therapies for women. Further studies are needed to address this gap and recommend optimal antithrombotic therapy post-PCI for women.

Racial Differences in Bleeding Risk: An Ecological Epidemiological Study Comparing Korea and United Kingdom Subjects.

This study aimed to evaluate racial differences in bleeding incidence by conducting an ecological epidemiological study using data from Korea and the United Kingdom. We included healthy participants from the Korean National Health Insurance Service-Health Screening and the UK Biobank who underwent health examinations between 2006 and 2010 and had no comorbidities or history of medication use. Finally, 112,750 East Asians (50.7% men, mean age 52.6 years) and 210,995 Caucasians (44.7% men, mean age 55.0 years) were analyzed. The primary outcome was composed of intracranial hemorrhage (ICH) and bleeding from the gastrointestinal, respiratory, and genitourinary systems. During the follow-up, primary outcome events occurred in 2,110 East Asians and in 6,515 Caucasians. East Asians had a 38% lower 5-year incidence rate compared with Caucasians (3.88 vs. 6.29 per 1,000 person-years; incidence rate ratio [IRR]: 0.62, 95% confidence interval [CI]: 0.59-0.65). East Asians showed a lower incidence of major bleeding (IRR: 0.86, 95% CI: 0.81-0.91), bleeding from the gastrointestinal (IRR: 0.53, 95% CI: 0.49-0.56), and genitourinary systems (IRR: 0.49, 95% CI: 0.44-0.53) compared with Caucasians. The incidence rates of ICH (IRR: 3.20, 95% CI: 2.67-3.84) and bleeding from the respiratory system (IRR: 1.28, 95% CI: 1.11-1.47) were higher in East Asians. Notably, East Asians consuming alcohol ≥3 times/week showed a higher incidence of the primary outcome than Caucasians (IRR: 1.12, 95% CI: 1.01-1.25). This ecological study revealed significant racial differences in bleeding incidence, influenced by anatomical sites and lifestyle habits, underscoring the need for tailored approaches in bleeding management based on race.

Evaluating the effect of inequalities in oral anti-coagulant prescribing on outcomes in people with atrial fibrillation

Abstract Aims Whilst anti-coagulation is typically recommended for thromboprophylaxis in atrial fibrillation (AF), it is often never prescribed or prematurely discontinued. The aim of this study was to evaluate the effect of inequalities in anti-coagulant prescribing by assessing stroke/systemic embolism (SSE) and bleeding risk in people with AF who continue anti-coagulation compared with those who stop transiently, permanently, or never start. Methods and results This retrospective cohort study utilized linked Scottish healthcare data to identify adults diagnosed with AF between January 2010 and April 2016, with a CHA2DS2-VASC score of ≥2. They were sub-categorized based on anti-coagulant exposure: never started, continuous, discontinuous, and cessation. Inverse probability of treatment weighting-adjusted Cox regression and competing risk regression was utilized to compare SSE and bleeding risks between cohorts during 5-year follow-up. Of an overall cohort of 47 427 people, 26 277 (55.41%) were never anti-coagulated, 7934 (16.72%) received continuous anti-coagulation, 9107 (19.2%) temporarily discontinued, and 4109 (8.66%) permanently discontinued. Lower socio-economic status, elevated frailty score, and age ≥ 75 were associated with a reduced likelihood of initiation and continuation of anti-coagulation. Stroke/systemic embolism risk was significantly greater in those with discontinuous anti-coagulation, compared with continuous [subhazard ratio (SHR): 2.65; 2.39–2.94]. In the context of a major bleeding event, there was no significant difference in bleeding risk between the cessation and continuous cohorts (SHR 0.94; 0.42–2.14). Conclusion Our data suggest significant inequalities in anti-coagulation prescribing, with substantial opportunity to improve initiation and continuation. Decision-making should be patient-centred and must recognize that discontinuation or cessation is associated with considerable thromboembolic risk not offset by mitigated bleeding risk.

External Validation of the OAC3-PAD Bleeding Score in a Nationwide Population of Patients Undergoing Invasive Treatment for Peripheral Arterial Disease

The OAC3-PAD score was developed to predict bleeding risk in patients with lower extremity peripheral arterial disease (PAD), but its performance in concomitant international cohorts is largely unknown. This study aimed to validate the OAC3-PAD score in an unselected nationwide population of patients undergoing invasive treatment for symptomatic PAD. This was a nationwide cohort study including all patients who underwent a first revascularisation procedure or major amputation for symptomatic PAD in Denmark from 2000 - 2021. The study population was stratified based on OAC3-PAD score, and the one year risk of major bleeding was assessed, accounting for the competing risk of death. The score performance was evaluated using calibration plots, C statistic, Brier score, and the index of prediction accuracy (IPA). A total of 52 016 patients were included (mean age 71 years, 43.8% female). The one year risk of major bleeding increased with higher OAC3-PAD score, ranging from 1.6% (95% confidence interval [CI] 1.4 - 1.8%) to 2.3% (95% CI 2.0 - 2.5%), 3.5% (95% CI 3.2 - 3.8%), and 5.2% (95% CI 4.8 - 5.6%) for patients with low, low moderate, moderate high, and high score, respectively. Using patients with low risk as reference, the OAC3-PAD score effectively categorised patients, demonstrating statistically significant differences in bleeding risk acrossstrata. However, the score showed modest discriminative performance, with a C statistic of 65% (95%CI 63 - 66%) and a Brier score of 2.6% (95% CI 2.5 - 2.7%). Nevertheless, it performed significantly better than the null model, as indicated by an IPA of 3.1%. Among patients who underwent invasive treatment for symptomatic PAD in routine care, the OAC3-PAD score was associated with greater risk of major bleeding with increasing score level. However, its discriminatory ability was modest, and the clinical utility remains to be determined.

Validation of the PRECISE-DAPT score in a population-based sample of patients undergoing percutaneous coronary intervention with stent implantation

Abstract Background Dual antiplatelet therapy (DAPT) after coronary stenting reduces the risk of recurrent ischemia but increases bleeding risk. The PRECISE-DAPT score was developed using data from clinical trials to identify individuals at high bleeding risk who may benefit from shorter DAPT duration. Although use of the PRECISE-DAPT score is recommended in clinical guidelines, its applicability to patients seen in routine clinical practice is uncertain. Purpose To assess the performance of the PRECISE-DAPT score in a population-based cohort of patients undergoing coronary stenting. Methods We calculated the PRECISE-DAPT score in patients enrolled in the Swedish register of cardiac care (SWEDEHEART) who underwent coronary stenting and received DAPT in an urban region in Sweden between January 1, 2013, and December 31, 2018. Patients were followed from day 30 after discharge after coronary stenting until a bleeding event (TIMI major/minor bleeding using ICD-codes for bleeding and data on changes in hemoglobin levels from healthcare registers), an ischemic event (myocardial infarction/ischemic stroke), discontinuation of DAPT, death, 12 months after stenting, or end of study period. We assessed the score’s discrimination and estimated rates of bleeding and ischemic events in groups of patients categorized using the score’s decision rule for "high bleeding risk" (score ≥25). We then compared bleeding rates in groups of patients categorized based on their score with those observed in the clinical trials used to derive the PRECISE-DAPT score. Results Of the 8,348 patients (mean (SD) age 67 (11) years; 27% women) included in the study, 2,001 (24%) were categorized as "high bleeding risk" (Figure 1). The PRECISE-DAPT score had a moderate discrimination (c-statistic 0.64, 95% CI, 0.56– 0.71) for bleeding. Patients with "high bleeding risk", compared to those not at "high bleeding risk", had a higher rate of bleeding (2.0 vs 0.9 events per 100 patient years; hazard ratio 2.17, 95% CI 1.29–3.65) and a higher rate of ischemic events (12.8 vs 9.0 events per 100 patient years; hazard ratio, 1.33, 95% CI 1.10–1.61). Patients with "high bleeding risk" in our study population had lower rates of bleeding as compared with those at "high bleeding risk" in the clinical trials used to derive the score. Rates of bleeding in other risk categories were largely similar to those in the clinical trials. (Figure 2). Conclusion In a population-based cohort from routine clinical practice in Sweden, the PRECISE-DAPT score identified patients with increased bleeding risk, although those patients also had an increased ischemic risk. Differences in bleeding rates among those categorized as "high bleeding risk" across patient populations may mean that the absolute risk differences in bleeding risk for short vs long DAPT duration demonstrated in the clinical trials used to derive the PRECISE-DAPT score may not be directly applicable to patients seen in routine clinical practice.

Abstract 19017: Peri-Operative Bridging Requirement for Patients Chronically Taking Direct Oral Anticoagulants (DOACS) or Vitamin-K Antagonists (VKA) Before Undergoing the Elective Procedure: A Systematic Review and Meta-Analysis

Introduction: Many patients undergo elective interventions/surgical procedures while being on direct oral anticoagulants (DOACs) or vitamin-K antagonists (VKA) chronically. There is limited data on peri-procedural management of DOACs in patients undergoing elective procedures. It is also unclear if there is any role of peri-procedural bridging in patients on chronic VKA therapy. We conducted this study to evaluate the efficacy and safety of DOACs (continued vs. interrupted)and VKAs (with vs. without bridging) among patients undergoing elective procedures. Methods: This systematic literature review was conducted according to PRISMA guidelines until 10 th June 2023. The following inclusion criteria were used: adults, chronic use of VKAs or DOACs, elective procedures, and clinical trials. Primary endpoints were major bleeding, stroke, MI, and VTE. A generic variance random effects model was used to estimate odds ratios using CMA III. Heterogeneity and quality of studies were quantified via I 2 statistic and GRADE score, respectively. Results: 14 clinical trials were included (n=15683). There was no difference in the risk of major bleeding (OR: 1.06, 95% CI: 0.65 -1.7, I2: 46%) or risk of stroke(OR: 1.10, 95% CI: 0.66 - 1.84, I2: 0%) whether DOACs were held or continued respectively. Among patients on VKA, there was no difference in risk of major bleeding in bridging vs. no bridging groups (OR: 2.02, 95% CI: 0.87 - 4.71, I2:75%). There was no difference in the rates of stroke (OR: 0.44, 95% CI: 0.12 -1.58, I2: 0%), MI (OR: 1.64, 95% CI: 0.76 - 3.53, I2: 0%), and VTE (OR: 1.26,95% CI: 0.31 - 5.01, I2: 0%). The quality of included studies was low to moderate. Conclusion: Patients undergoing elective procedures and chronically taking DOACs have a similar risk of major bleeding and stroke when DOACs are continued or interrupted peri procedurally. Similarly, among patients on VKA who were bridged or not bridged, there was no difference in risk of bleeding, stroke, MI or VTE.

Safety and Efficacy of Extended Postdischarge Venous Thromboembolism Prophylaxis in Microsurgical Breast Reconstruction.

The PearlDiver database was queried for MBR patients who did not receive postdischarge VTE prophylaxis (cohort 1) and MBR patients discharged with enoxaparin for at least 14 days (cohort 2), then queried for hematoma, deep venous thrombosis (DVT), and/or pulmonary embolism. Concurrently, a systematic review was undertaken to identify studies investigating VTE with postoperative chemoprophylaxis. In total, 13,541 patients in cohort 1 and 786 patients in cohort 2 were identified. The incidence of hematoma, DVT, and pulmonary embolism were 3.51%, 1.01%, 0.55% in cohort 1, and 3.31%, 2.93%, and 1.78% in cohort 2, respectively. There was no significant difference in hematoma between these two cohorts (P = 0.767); however, a significantly lower rate of DVT (P < 0.001) and pulmonary embolism (P < 0.001) occurred in cohort 1. Ten studies met systematic review inclusion. Only three studies reported significantly lower VTE rates with postoperative chemoprophylaxis. Seven studies found no difference in bleeding risk. This is the first study utilizing a national database and a systematic review to investigate extended postoperative enoxaparin in MBR. Overall, rates of DVT/PE seem to be declining compared with previous literature. The results of this study suggest that there remains a lack of evidence supporting extended postoperative chemoprophylaxis, although the therapy appears safe in that it does not increase bleeding risk.

Dual Antiplatelet Therapy Does Not Increase Bleeding Risk in Percutaneous Gastrostomy Tube Placement: Network Meta-Analysis.

Gastrostomy tube (G tube) is a commonly performed procedure for nutritional support. Current guidelines recommend discontinuation of dual antiplatelet therapy (DAPT) prior to G tube placement to reduce bleeding risk. We aim to compare bleeding risk in single, dual and no antiplatelet therapy during G tube placement. We searched PubMed, Embase, Cochrane, and Web of Sciences to include comparative studies evaluating single antiplatelet (aspirin, clopidogrel), dual antiplatelet (DAPT, aspirin and clopidogrel), and no antiplatelet therapy. Direct as well as network meta-analyses comparing these arms were performed. Risk Differences (RD) with confidence intervals were calculated. 12 studies with 8471 patients were included. On direct meta-analysis, there was no significant difference noted between DAPT compared to Aspirin (RD 0.001 95% CI - 0.012 to 0.014, p = 0.87), Clopidogrel (RD 0.001 95% CI - 0.009 to 0.010, p = 0.92) or no antiplatelet group (RD 0.007 95% CI - 0.011 to 0.026, p = 0.44). Results were consistent on network meta-analysis and no difference was noted in bleeding rates when comparing DAPT with Aspirin (RD 0.001, 95% CI - 0.007 to 0.01, p = 0.76), Clopidogrel (RD 0.001, 95% CI - 0.01 to 0.011, p = 0.90) and no antiplatelet group (RD 0.002, 95% CI - 0.007 to 0.012, p = 0.62). There is no significant difference in bleeding risk between DAPT, single antiplatelet or no antiplatelet therapy on a population level. On an individual level, risk of ischemic events should be weighed against the risk of bleeding based on patient circumstances and risk profile. Our findings offer to provide additional data to make an informed decision between patients and physicians to make clinical decisions by assessing individual risks and benefits for optimal care of complex patients.

The Risk of Endoscopy-Related Bleeding in Patients with Liver Cirrhosis: A Retrospective Study.

Background and Objectives: The risk of bleeding after endoscopic procedures in patients with liver cirrhosis remains unclear because of secondary blood coagulation disorders. In this study, we used various indices to evaluate the risk of bleeding in patients with cirrhosis. Materials and Methods: Patients with liver cirrhosis aged ≥18 years who underwent endoscopic interventions at Kyung Hee University Hospital at Gangdong between February 2007 and September 2021 were included. Clinical information, including demographic data, laboratory results, the presence of cirrhosis complications, and the degree of fibrosis, was checked and evaluated based on medical records. Results: A total of 101 patients with cirrhosis were analyzed. A total of 16 of the 101 patients (15.8%) experienced bleeding after the endoscopic procedure. One patient (0.99%) presented with spurting, while the others presented with mild oozing. All patients underwent hemostatic procedures using hemoclips. The presence of a varix significantly increased post-endoscopic bleeding (p = 0.03). Patients with FIB &gt; 3.25 showed a statistically significant bleeding tendency (p = 0.00). Conclusions: There was no significant difference in bleeding risk according to the platelet count, prothrombin time, Child-Pugh score, and model for end-stage liver disease (MELD). Considering the degree of liver fibrosis and the invasiveness of the planned procedure, most endoscopic procedures can be performed safely but should be further evaluated in a cohort with a larger sample size.

Abstract 10131: Real World Comparative Outcomes From Left Atrial Appendage Occlusion versus Anticoagulation Among Females and Males

Introduction: Clinical decision-making around AF-related stroke risk management is complicated by the widely available and safe direct acting oral anticoagulants (AC) and uncertain long term risks of left atrial appendage occlusion (LAAO) in patients who are older and more female than clinical trial participants. Hypothesis: Among matched sex-stratified Medicare beneficiaries with AF, there is no difference in risk of mortality, stroke, and bleeding associated with LAAO versus AC alone. Methods: Medicare beneficiaries with AF and CHA2DS2VASc of 2 (males) or 3 (females) (2015-2019) were divided into those who underwent LAAO or received AC only. LAAO and AC patients were propensity score matched 1:1 within sex subgroups based on available characteristics. A Cox proportional hazards model was used to model the survival time from the LAAO implant date to evaluate the comparative risks of mortality, stroke/thromboembolism, and any bleeding events based on ICD-10 codes. Results: Matching sex-stratified AC and LAAO patients was successful (SMD &lt; 10% on all variables). Average follow-up was 1 year. Among females (n=4,085; mean 76 years, CHA2DS2VASc 5.1), LAAO was associated with reduced risk of mortality and stroke/thromboembolism (HR 0.51 95% CI 0.45-0.58; HR 0.66 95% CI 0.56-0.77, p&lt;0.0001) compared with AC; similar findings were observed among males (n=5,378; mean 75.3 years, CHA 2 DS 2 VASc 4.1) regarding mortality and stroke/ thromboembolism (HR 0.54 95% CI 0.49-0.60; HR 0.65 95% CI 0.55-0.76, p&lt;0.0001). Comparative bleeding risk varied over time with LAAO associated with greater risk early then lesser risk (females HR 1.03 95% CI 0.92-1.16; males HR 1.05 95% CI 0.95-1.17). (Figure) Conclusion: Within sex subgroups during an average of 1 year follow up, LAAO was associated with a reduced risk of mortality and stroke/thromboembolism when compared with AC alone among Medicare beneficiaries with AF. There was no difference in the risk of bleeding between LAAO and AC groups.

Risk of Postdischarge Bleeding From Dual Antiplatelet Therapy After Percutaneous Coronary Intervention Among US Black and White Adults.

Background Dual antiplatelet therapy after percutaneous coronary intervention reduces myocardial infarctions but increases bleeding. The risk of bleeding may be higher among Black patients for unknown reasons. Bleeding risk scores have not been validated among Black patients. We assessed the difference in bleeding risk between Black and White patients along with the performance of the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Anti Platelet Therapy, Patterns of Nonadherence to Antiplatelet Regimens in Stented Patients, and Academic Research Consortium for High Bleeding Risk scores among both groups. Methods and Results This was a single-center prospective study of patients who underwent percutaneous coronary intervention (2014-2019) and were followed for 1 year. The outcome was postdischarge Bleeding Academic Research Consortium 2 to 5 bleeding. Incidence rates were reported. Cox proportional hazards models measured the effect of self-reported Black race on bleeding and determined the predictors of bleeding among 19 a priori variables. The 3 risk scores were assessed among Black and White patients separately using the Harrell concordance index. Of 1529 included patients, 342 (22.4%) self-reported as being Black race. Unadjusted bleeding rates were 22.7 per 100 person-years among Black patients versus 16.3 among White patients (hazard ratio, 1.41 [95% CI, 1.00-2.00], P=0.052). Predictors of bleeding were age, glomerular filtration rate <30 mL/min per 1.73 m2, prior bleeding, ticagrelor or prasugrel use, and anticoagulant use. Among Black and White patients, respectively, the C-indexes were the following: 0.644 versus 0.600 for Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Anti Platelet Therapy (P<0.001 for both), 0.620 versus 0.612 for Patterns of Nonadherence to Antiplatelet Regimens in Stented Patients (P=0.003 and P<0.001, respectively), and 0.600 versus 0.598 for Academic Research Consortium for High Bleeding Risk (P=0.006 and P<0.001, respectively). Conclusions The risk of dual antiplatelet therapy-associated postdischarge Bleeding Academic Research Consortium 2 to 5 bleeding was not significantly different between self-reported Black and White patients. Bleeding risk scores performed similarly among both groups.

122. Anticoagulation therapy in cervical spine fractures: insights from a large health care database analysis

<h3>BACKGROUND CONTEXT</h3> The type of chemical thromboembolic event (TEE) prophylaxis to administer following cervical spine fracture is a matter of contention. The risk of TEE must be weighed against the risk of bleeding complications from the therapy itself. Patients with cervical fractures may be at greater risk of devastating bleeding complications such as epidural hematoma, particularly after surgical decompression. The goal of this database study was to provide an accurate estimate to serve as a reference in the literature for the incidence of TEE in these patients. <h3>PURPOSE</h3> The purpose of this study was to (1) evaluate comorbidity burden, (2) rate of thromboembolic events, (3) rate of anemia and transfusion events, and (4) evaluate utilization rates of various forms of pharmacologic prophylaxis following cervical spine fracture. <h3>STUDY DESIGN/SETTING</h3> Retrospective database study. <h3>PATIENT SAMPLE</h3> The study included 5,871 patients who were treated with anticoagulation therapy within 6 months of cervical spine fracture identified from the Humana Insurance Database. <h3>OUTCOME MEASURES</h3> (1) Thromboembolic events, (2) transfusion proportion, and (3) anemia proportion, based on various types of AC therapy. <h3>METHODS</h3> A retrospective review of the Humana insurance database from 2007 to 2016 was performed to identify patients who sustained a fracture of the cervical spine and prescribed anticoagulation therapy. Patients were subdivided by the type of agent prescribed: aspirin/anti platelet therapy, warfarin, heparin/low molecular weight heparin (LMWH), or factor Xa inhibitors. Each cohort was longitudinally tracked for 6 months following surgery for occurrence of deep venous thrombosis (DVT), pulmonary embolism (PE), stroke, anemia or blood transfusion. Chi-square test was used to determine significance. <h3>RESULTS</h3> A total of 5,871 patients were included. Demographics of each cohort were statistically similar. Patients receiving warfarin had a greater CCI compared to the other cohorts (4.1; p < 0.05). Patients on aspirin/anti-platelet therapy were the least likely to develop any TEE (2.1%; p < 0.05). There was no statistically significant difference found between cohorts in regard to the incidence of stroke, transfusion rate or anemia. <h3>CONCLUSIONS</h3> Aspirin and anti-platelet anticoagulation therapy after cervical fracture had the least number of thromboembolic events when used within 6 months compared to other common forms of anticoagulation, without any statistically significant difference in bleeding risk. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients: a meta-analysis of multicenter randomized controlled trials.

Arterial and venous thrombotic events in COVID-19 cause significant morbidity and mortality among patients. Although international guidelines agree on the need for anticoagulation, it is unclear whether full-dose heparin anticoagulation confers additional benefits over prophylactic-dose anticoagulation. This systematic review and meta-analysis aimed to investigate the efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients. We searched Pubmed/Medline, EMBASE, Clinicaltrials.gov, medRxiv.org and Cochrane Central Register of clinical trials dated up to April 2022. Randomized controlled trials (RCTs) comparing full-dose heparin anticoagulation to prophylactic-dose anticoagulation or standard treatment in hospitalized non-critically ill COVID-19 patients were included in our pooled analysis. The primary endpoint was the rate of major thrombotic events and the co-primary endpoint was the rate of major bleeding events. We identified 4 studies, all of them multicenter, randomizing 2926 patients. Major thrombotic events were 23/1524 (1.5%) in full-dose heparin anticoagulation versus 57/1402 (4.0%) in prophylactic-dose [relative risk (RR) 0.39; 95% confidence interval (CI) 0.25–0.62; p˂0.01; I2 = 0%]. Clinical relevant bleeding events occurred in 1.7% (26/1524) among patients treated with heparin full anticoagulation dose compared to 1.1% (15/1403) in prophylactic-dose group (RR 1.60; 95% CI 0.85–3.03; p = 0.15; I2 = 20%). Mortality was 6.6% (101/1524) versus 8.6% (121/1402) (RR 0.63; 95% CI 0.33–1.19; p = 0.15). In this meta-analysis of high quality multicenter randomized trials, full-dose anticoagulation with heparin was associated with lower rate of major thrombotic events without differences in bleeding risk and mortality in hospitalized non critically ill COVID-19 patients.Study registration PROSPERO, review no. CRD42022301874.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11239-022-02681-x.

Different Antiplatelet Strategies for Radial Artery Protection After Transradial Coronary Angiography-A Prospective Observational Cohort Study.

IntroductionRadial artery occlusion (RAO) after transradial access is a common thrombotic complication. A meta-analysis has proven that RAO incidence in transradial coronary angiography (TRCA) settings was significantly higher than that in percutaneous coronary intervention settings. This prospective observational cohort aimed to evaluate radial artery protection after TRCA with different antiplatelet strategies.MethodsA total of 2,316 patients undergoing TRCA was enrolled and divided into two groups: single-antiplatelet and dual-antiplatelet groups. Radial artery patency was evaluated by ultrasound before, at 24 h, and 30 days after TRCA. The primary endpoint was RAO incidence at 30 days after TRCA.ResultsA total of 66 RAO was found on ultrasonography at 30-day follow-up (incidence: 2.8%). In the dual-antiplatelet group, the rate of RAO was significantly lower compared with the single-antiplatelet group (1.8 vs. 4.0%; odds ratio (OR): 0.41; 95% confidence interval (CI): 0.24–0.70; p = 0.001). The rate of self-recanalization in the dual-antiplatelet group was significantly higher than that in the single-antiplatelet group (73.68 vs. 44.12%, p < 0.001). However, there was no statistical difference in delayed occlusion of radial artery between the two groups (0.5 vs. 0.2%, p = 0.140). Unexpectedly, this study also showed no significant difference in bleeding risk between the groups.ConclusionDual-antiplatelet therapy for 1 month after TRCA was associated with a reduced risk of RAO and deemed safe.

Pre-existing cardiovascular disease increases risk of atrial arrhythmia and mortality in cancer patients treated with Ibrutinib

BackgroundIbrutinib is a Bruton’s tyrosine kinase inhibitor used in the treatment of hematological malignancies. The most common cardiotoxicity associated with ibrutinib is atrial arrhythmia (atrial fibrillation and flutter). It is known that patients with cardiovascular disease (CVD) are at an increased risk for developing atrial arrhythmia. However, the rate of atrial arrhythmia in patients with pre-existing CVD treated with ibrutinib is unknown.ObjectiveThis study examined whether patients with pre-existing CVD are at a higher risk for developing atrial arrhythmias compared to those without prior CVD.MethodsA single-institution retrospective chart review of patients with no prior history of atrial arrhythmia treated with ibrutinib from 2012 to 2020 was performed. Patients were grouped into two cohorts: those with CVD (known history of coronary artery disease, heart failure, pulmonary hypertension, at least moderate valvular heart disease, or device implantation) and those without CVD. The primary outcome was incidence of atrial arrhythmia, and the secondary outcomes were all-cause mortality, risk of bleeding, and discontinuation of ibrutinib. The predictors of atrial arrhythmia (namely atrial fibrillation) were assessed using logistic regression. A Cox-Proportional Hazard model was created for mortality.ResultsPatients were followed for a median of 1.1 years. Among 217 patients treated with ibrutinib, the rate of new-onset atrial arrhythmia was nearly threefold higher in the cohort with CVD compared to the cohort without CVD (17% vs 7%, p = 0.02). Patients with CVD also demonstrated increased adjusted all-cause mortality (OR 1.9, 95% CI 1.06-3.41, p = 0.01) and decreased survival probability (43% vs 54%, p = 0.04) compared to those without CVD over the follow-up period. There were no differences in risk of bleeding or discontinuation between the two cohorts.ConclusionsPre-existing cardiovascular disease was associated with significantly higher rates of atrial arrhythmia and mortality in patients with hematological malignancies managed with ibrutinib.

Abstract 12895: Superior Effectiveness and Safety of Ticagrelor in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Nationwide Registry-Based Study

Introduction: Dual antiplatelet therapy with aspirin and a P2Y 12 inhibitor is recommended following PCI for ACS. The optimal choice of P2Y 12 inhibitor remains debated. We compared effectiveness and safety of clopidogrel, ticagrelor, and prasugrel in a large, nationwide cohort of patients with ACS undergoing PCI. Methods: Registry-based study of first-time ACS patients who underwent PCI ≤7 days of admission and redeemed a prescription of a P2Y 12 inhibitor ≤30 days of the index event. The primary outcome was major adverse cardiovascular events (MACE): a composite of cardiovascular death, recurrent myocardial infarction, stroke, or repeat revascularization at 12 months. The safety outcome was bleeding requiring hospitalization at 12 months. Multivariable logistic regression with average treatment effect modeling was used to calculate standardized absolute and relative risks for outcomes across age, sex, comorbidity, bleeding, and concomitant anticoagulant therapy distributions. Results: We included 26,997 patients; 6,585 were discharged on clopidogrel, 18,425 on ticagrelor, and 1,987 on prasugrel. Corresponding median ages were 70, 64, and 59 years (p&lt;0.001). Patients in the clopidogrel group were more likely to have had a prior bleeding episode (p&lt;0.001). Adjusted relative risks of MACE were 0.80 for ticagrelor vs clopidogrel (p&lt;0.001), 0.85 for prasugrel vs clopidogrel (p&lt;0.001), and 1.05 for prasugrel vs ticagrelor (p=0.22). Adjusted relative risks of bleeding were 0.82 for ticagrelor vs clopidogrel (p=0.001), 1.07 for prasugrel vs clopidogrel (p=0.56), and 1.30 for prasugrel vs ticagrelor (p=0.03). While statistically significant, the absolute differences in risk of bleeding among groups were modest (Figure). Conclusion: Ticagrelor and prasugrel were associated with lower risk of MACE than clopidogrel but did not significantly differ from each other. Ticagrelor was associated with a lower risk of bleeding than both clopidogrel and prasugrel.

Therapeutic efficacy of heparin and direct factor Xa inhibitors in cancer-associated cryptogenic ischemic stroke with venous thromboembolism

BackgroundAnticoagulation therapy, especially using heparin or recently developed oral direct factor Xa inhibitors (DiXals), is recommended as first-line treatment for cancer-related venous thromboembolism (VTE). However, the preventive efficacy of these anticoagulants for cancer-associated ischemic stroke is still unknown. We retrospectively investigated the efficacy of subcutaneous unfractionated heparin (UFH) and DiXals for preventing the recurrence of cancer-associated cryptogenic ischemic stroke with VTE. MethodsWe retrospectively studied consecutive patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE who received subcutaneous UFH or oral DiXaIs at 9 hospitals. ResultFifty-three patients (24 treated with UFH and 29 treated with DiXaIs) were enrolled. Of these, 47 demonstrated systemic metastasis (cancer stage IV). During 30-day follow-up after initiation of anticoagulation therapy, recurrent ischemic stroke was observed in only 1 patient (4%) in the UFH group and in 9 patients (31%) in the DiXal group. The incidence of major bleeding complications was similar between the 2 groups (4% and 10%, respectively). The cumulative risk of ischemic stroke recurrence within 30 days was lower with UFH than with DiXals (competing risk analysis, p = 0.008). In the DiXal group, patients who experienced recurrence showed significantly higher D-dimer levels than those without recurrence. ConclusionIn patients with cancer-associated cryptogenic ischemic stroke and comorbid VTE, UFH demonstrated a lower rate of recurrent ischemic stroke than DiXaIs, and there were no differences in bleeding risk between the 2 treatments. D-dimer levels at stroke onset increased the risk of recurrence in the DiXal group but not in the UFH group.

The Safety of Aspirin Vs. Direct Oral Anticoagulants: A Meta-Analysis of Currently Published Clinical Trials

Introduction:Several prior analyses have suggested that the use of warfarin leads to no observable difference in bleeding events when compared to aspirin. Although direct oral anticoagulants (DOACs) have been shown to be consistently safer than warfarin, data comparing the safety and efficacy of DOACs vs. aspirin has been sparse until recently. To date, two large randomized trials, EINSTEIN CHOICE and AVERROES, have compared DOACs to aspirin for secondary VTE prevention and prevention of thrombotic events in patents with atrial fibrillation respectively. Although DOACs were proven more effective then aspirin for both indications, the comparative bleeding risk between the two interventions remained unclear. In order to evaluate the safety of aspirin vs. DOACs we performed a meta-analysis of patients receiving aspirin vs. full dose DOAC within the two aforementioned trials.Methods:Using data from two recently-published, phase III trials– EINSTEIN CHOICE and AVERROES– we performed a meta-analysis using a Mantel-Haenszel random-effects model. Odds Ratios (OR) were generated along with forest plots. All analysis was performed with Review Manager (version 5.3 The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).Results:In total, 3854 patients were treated with a therapeutic dose DOAC (apixaban 5mg BID or rivaroxaban 20mg daily) and 3876 were treated with varied doses of aspirin (81mg [46.9%], 100mg [27.6%], 162mg [18.5%], 243mg [1.9%], 324mg [5.0%], and unknown dose [0.2%]). Our analysis detected no statistically significant difference in major bleeding events (1.27% vs. 1.07%; p=0.4) or clinically-relevant, non-major bleeding events (3.22% vs. 2.65%; p=0.14) between the two groups (Table 1).Conclusion:This analysis suggests that aspirin is not appreciably safer than full dose DOACs in terms of bleeding risk. Given the size of this analysis, if a true difference in bleeding risk does exist, it is likely small and not clinically relevant. In addition to being significantly less effective, these results contradict any notion that aspirin is a safer alternative in terms of bleeding risk. Therefore, given the superior efficacy of DOACs for secondary VTE prevention and stroke prevention in atrial fibrillation, DOACs should always be preferentially used over aspirin in these populations. Future guidelines for clinical practice should reflect the evidence that aspirin is neither safer nor more effective for either indication. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Abstract No. 530 Is there a difference in bleeding risk for small-bore versus large-bore mechanical thrombectomy? A systematic review of major complications

There are numerous devices that may be used for mechanical thrombectomy. The purpose of this study was to conduct a systematic review of complications with mechanical thrombectomy for pulmonary embolism (PE). A systematic search identified all studies in which patients underwent mechanical thrombectomy for PE. Studies with < 6 patients were excluded. Study details collected included patient demographics, clinical severity (massive vs. submassive), device type and use of intraprocedural tPA for thrombolysis. Major complications were the main outcome measured collected. 26 studies consisting of 462 total patients (221 women and 241 men) with a mean age of 54.0 years were identified. 13 studies had only patients with massive PEs (n = 138), 1 study with only submassive PEs (n = 104), and 12 studies with both massive and submassive PEs (n = 220). 1 Large-bore mechanical thrombectomy study evaluated the 26 Fr AngioVac system and 2 studies used the 20 Fr or greater Inari FlowTriever . The remaining 23 studies were composed of small-bore devices ranging from 6 to 8 Fr, which included AngioJet (n = 11), Aspirex/Rotarex (n = 4), Amplatz Thrombectomy Device (n = 3), Hydrolyser (n = 3) and Indigo (n = 2). 2 studies used intraprocedural tPA (n = 14), 11 studies did not use any tPA (n = 291), and 13 studies used some intraprocedural tPA (n = 157). Subgroup analysis of studies that did not use intraprocedural tPA yielded similar major bleeding rates of 3.2% (5/155) for large-bore thrombectomy and 1.5% (2/136) for small-bore thrombectomy (chi-square statistic 0.9506, P-valueP 0.33) [sic]. Major complication rates were 3.9% (6/155) for large-bore thrombectomy and 2.2% (3/136) for small-bore thrombectomy (chi-square statistic 0.6701, P-valueP 0.41) [sic].Conclusions: There are no randomized controlled trials comparing the multiple mechanical thrombectomy devices for management of PE. This systematic review of available case studies shows that major bleeding and major complication rates for sub-group analysis of large-bore and small-bore thrombectomy devices are low and are comparable.