Difference In Bleeding Events Research Articles

Intracoronary Versus Intravenous Low-Dose Tirofiban in Patients With ST-Elevation Myocardial Infarction: A Meta-Analysis of Randomised Controlled Trials

This meta-analysis aimed to evaluate the effects of intracoronary (IC) low-dose tirofiban versus intravenous (IV) administration on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). All published randomised controlled trials (RCTs) comparing the effects of IC low-dose tirofiban (a bolus of ≤10 ug/kg) versus IV administration in patients with STEMI were identified by searching PubMed, EMBASE, Cochrane Library, and ISI Web of Science from inception to June 2023, with no language restriction. The risk ratio (RR) with 95% confidence intervals (CI) and the weighted mean difference (WMD) with 95% CI were calculated. Eleven RCTs involving 1,802 patients were included. Compared with the IV group, IC low-dose tirofiban was associated with improved major adverse cardiac events rate (RR 0.595, 95% CI 0.442-0.802; p=0.001), left ventricular ejection fraction (WMD 1.982, 95% CI 0.565-3.398; p=0.006), thrombolysis in myocardial infarction (TIMI) flow grade (RR 1.065, 95% CI 1.004-1.131; p=0.037), and TIMI myocardial perfusion grade (RR 1.194, 95% CI 1.001-1.425; p=0.049). The two groups had no significant difference in bleeding events (RR 0.952, 95% CI 0.709-1.279; p=0.745). Intracoronary low-dose tirofiban administration may be a safe and effective alternative to IV administration in STEMI patients.

Evaluation of Apixaban standard dosing in underweight patients with non-valvular atrial fibrillation: a retrospective cohort study

BackgroundRecent guidelines recommend using direct oral anticoagulants (DOACs) as first-line agents in patients with non-valvular atrial fibrillation (NVAF). Research is currently investigating the use of Apixaban in underweight patients, with some results suggesting altered pharmacokinetics, decreased drug absorption, and potential overdosing in this population. This study examined the effectiveness and safety of standard Apixaban dosing in adult patients with atrial NVAF weighing less than 50 kg.MethodsThis is a retrospective cohort study conducted at King Abdulaziz Medical City (KAMC); adult patients with a body mass index (BMI) below 25 who received a standard dose of Apixaban (5 mg twice daily) were categorized into two sub-cohorts based on their weight at the time of Apixaban initiation. Underweight was defined as patients weighing ≤ 50 kg, while the control group (Normal weight) comprised patients weighing > 50 kg. We followed the patients for at least one year after Apixaban initiation. The study’s primary outcome was the incidence of stroke events, while secondary outcomes included bleeding (major or minor), thrombosis, and venous thromboembolism (VTE). Propensity score (PS) matching with a 1:1 ratio was used based on predefined criteria and regression model was utilized as appropriate.ResultsA total of 1,433 patients were screened; of those, 277 were included according to the eligibility criteria. The incidence of stroke events was lower in the underweight than in the normal weight group at crude analysis (0% vs. 9.1%) p-value = 0.06), as well in regression analysis (OR (95%CI): 0.08 (0.001, 0.76), p-value = 0.002). On the other hand, there were no statistically significant differences between the two groups in the odds of major and minor bleeding (OR (95%CI): 0.39 (0.07, 2.03), p-value = 0.26 and OR (95%CI): 1.27 (0.56, 2.84), p-value = 0.40, respectively).ConclusionThis exploratory study revealed that underweight patients with NVAF who received standard doses of Apixaban had fewer stroke events compared to normal-weight patients, without statistically significant differences in bleeding events. To confirm these findings, further randomized controlled trials with larger sample sizes and longer observation durations are required.

Aspirin resistance in patients with ventricular assist devices-A follow-up study.

Despite combined anticoagulation therapy consisting of a vitamin K antagonist and an antiplatelet agent, thromboembolic complications often occur in patients with a left ventricular assist device (LVAD). In addition, bleeding events are also common. Resistance to antiplatelet drugs is a well-known phenomenon; however, the utilization of laboratory chemistry testing for the presence of such resistance, and then switching therapy, is controversial. We tested 132 patients with LVAD (HeartWare n = 57, HeartMate II n = 22, HeartMate 3 n = 53) on acetylsalicylic acid (ASA) therapy for resistance and followed them for a maximum of 7 years regarding pump thrombosis. Light transmission aggregometry (LTA) and impedance aggregometry (IPA) were performed for testing platelet function. We could show that patients with ASA resistance displayed an increased risk of pump thrombosis, regardless of the test used (LTA: OR = 6.20, CI [1.86-20.64], p = 0.003; IPA: OR = 12.14, CI [3.00-49.07], p < 0.001). In patients with a HeartMate 3, we could not detect any pump thrombosis associated with aspirin resistance. Furthermore, there was no significant difference in bleeding events between patients with ASA resistance and ASA responders. Laboratory testing of ASA resistance seems to be a good tool to detect an increased risk of pump thrombosis, at least for patients with a HeartWare or HeartMate II. The extent to which these thromboses can be prevented with a change of medication has to be investigated in further studies. No pump thrombosis was detected in patients with a HeartMate 3, and the question should be asked as to what constellation of underlying and concomitant diseases must be present to justify ASA therapy for these patients.

Safety of postdischarge extended venous thromboembolism prophylaxis after hepatopancreatobiliary surgery

The risk of venous thromboembolism (VTE) after hepatopancreatobiliary (HPB) surgery is high. Extended postdischarge prophylaxis in this patient population has been controversial. This study aimed to examine the safety of postdischarge extended VTE prophylaxis in patients at high risk of VTE events after HPB surgery. Adult patients risk stratified as very high risk of VTE who underwent HPB operations between 2014 and 2020 at a quaternary care center were included. Patients were matched 1:2 extended VTE prophylaxis to the control group (patients who did not receive extended prophylaxis). Analyses compared the proportions of adverse bleeding events between groups. A total of 307 patients were included: 103 in the extended prophylaxis group and 204 in the matched control group. Demographics were similar between groups. More patients in the extended VTE prophylaxis group had a history of VTE (9% vs 3%; P=.045). There was no difference in bleeding events between the extended VTE prophylaxis and the control group (6% vs 2%; P=.091). Of the 6 patients with bleeding events in the VTE prophylaxis group, 5 had gastrointestinal (GI) bleeding, and 1 had hemarthrosis. Of the 4 patients with bleeding events in the control group, 1 had intra-abdominal bleeding, 2 had GI bleeding, and 1 had intra-abdominal and GI bleeding. Patients discharged with extended VTE prophylaxis after HPB surgery did not experience more adverse bleeding events compared with a matched control group. Routine postdischarge extended VTE prophylaxis is safe in patients at high risk of postoperative VTE after HPB surgery.

Early in-hospital discontinuation of aspirin on the first post-procedural day after percutaneous coronary stent implantation in patients on direct oral anticoagulation.

Previous trials investigating antithrombotic therapy with a direct oral anticoagulant (DOAC) and a P2Y12 inhibitor after percutaneous coronary intervention (PCI), termed dual therapy, allowed a short period of triple therapy including a DOAC, a P2Y12 inhibitor, and aspirin. This study aimed to determine whether discontinuation of aspirin on the first post-procedural day is safe or causes ischemic events. Ischemic and bleeding events during hospitalization were investigated retrospectively in all patients treated with dual therapy (DOAC + P2Y12 inhibitor, designated as group 1) or triple therapy (DOAC + P2Y12 inhibitor+aspirin, designated as group 2) from day 1 after PCI at our center. Of 4,564 consecutive PCI procedures, 1,059 (23.2%) had an indication for OAC. Of these, 322 met the inclusion criteria for group 1 and 62 for group 2. Baseline characteristics, CHA2DS2-VASc and HAS-BLED scores showed no relevant differences between the two groups, and the main indication for DOAC therapy was atrial fibrillation in both groups. Approximately ¼ of patients were treated for acute coronary syndrome. The mean length of post-procedural hospitalization was 2.1 ± 2.5 and 2.2 ± 3.0 days in group 1 and 2, respectively (p = 0.305). One patient per group suffered a TIA (p = 0.297). There were no other ischemic events and no statistically significant differences in bleeding events. A subgroup analysis of cases hospitalized for ≥2 post-procedural days (group 1: 100 cases, mean 4.4 ± 3.4 days vs. group 2: 25 cases, mean 4.0 ± 4.1 days) confirmed these results. The initiation of dual therapy and thus discontinuation of aspirin on the first postprocedural day appears to be safe with respect to short-term ischemic events in a real-world population. Almost ¼ of patients undergoing PCI have an indication for OAC, highlighting the relevance of this issue.

Use of Eltrombopag for Post-CAR T Cytopenias: A Multi-Institutional Experience

Background: Cytopenias following chimeric antigen receptor T (CAR T) cell therapy are common and can be profound and/or prolonged, leading to increased morbidity and mortality. Supportive care is the mainstay of management but strategies to reduce the duration and severity of cytopenias have yet to be optimized. One such strategy extrapolated from experience in aplastic anemia is the use of thrombopoietin (TPO) receptor agonists, like eltrombopag. Eltrombopag has been used off-label for several years for this indication, however, limited data exists regarding the safety and efficacy of its use after CAR T-cell therapy. Methods: Patients ≥ 18 years of age treated with CAR T-cell therapy for either lymphoma or myeloma at two academic medical centers between January 2018 and January 2023 were included in a retrospective analysis. Use of eltrombopag was initiated at the KUMC for patients who had received CAR T and subsequently had persistent cytopenias at day +30 as evidenced by at least one of four criteria: grade 3 or 4 leukopenia, grade 4 thrombocytopenia, growth factor dependency, or platelet transfusion dependency. Use of eltrombopag was initiated at the MUSC for patients who had received CAR T and had grade 4 thrombocytopenia at day +21 and beyond post-CAR T infusion. Baseline patient and disease characteristics as well as variables describing safety and efficacy of eltrombopag for the treatment of persistent high-grade leukopenia and/or thrombocytopenia beyond day +21 post CAR T infusion were collected and summarized using descriptive statistics. Results: A total of 185 patients were included in this analysis. Of these, 163 (88%) experienced thrombocytopenia or leukopenia at day +30 post-CAR T infusion. A total of 42 patients met institutional criteria for eltrombopag treatment and initiated therapy. Median time to initiation of eltrombopag was 33 days (range 28-50) from infusion, with no significant differences between the two institutions (30 days at KUMC vs 36 days at MUSC, p=0.19). Median duration for the use of eltrombopag was 63 days (range 32-172) and KUMC used eltrombopag for a longer duration than MUSC (108 days vs 32 days, p=0.03). There were no statistically significant differences in bleeding events in the eltrombopag vs non-eltrombopag groups, p=0.053, and no reported cases of deep vein thrombosis or pulmonary embolism (DVT/PE) after initiating eltrombopag. Patients on eltrombopag were more likely to have infections (24 (57%) vs 42 (35%), p&amp;lt;0.01) and admission to intensive care unit (16 (38%) vs 20 (17%), p&amp;lt;0.01) when compared to the non-eltrombopag group. At day +30, 74 (45%) patients in the entire study population had grade 3 or higher leukopenia or thrombocytopenia, with 39 (93%) and 25 (29%) patients in the eltrombopag and non-eltrombopag groups with grade 3 or higher cytopenias, respectively ( p&amp;lt;0.001). By day +90, only 18 (35%) patients in the evaluable population had grade 3 or higher leukopenia or thrombocytopenia, with 12 (50%) and 6 (22%) patients in the eltrombopag and non-eltrombopag groups with grade 3 or higher cytopenias, respectively ( p=0.046). By day +180, all but ten patients in the evaluable population had not recovered to less than a grade 3 cytopenia with no significant difference in cytopenias between the two groups. With a median follow up of 12 months (range 1-34) for the entire patient population, median PFS was lower for the eltrombopag group (13 months) compared to the non-eltrombopag group (16 months, p=0.02). When stratified by disease, this association was observed only for the lymphoma patients, with a median PFS of 8.5 months in the eltrombopag group compared to a median PFS of 17 months in the non-eltrombopag group, p=0.01 (Table 1). Similarly, for the entire patient population, median OS was lower for the eltrombopag group (14 months) compared to the non-eltrombopag group (18 months, p=0.01). When stratified by disease, this association was observed only for the lymphoma patients, with a median OS of 14 months in the eltrombopag group compared to 18 months in the non-eltrombopag group ( p&amp;lt;0.01). Conclusions: In this first of its kind real-world experience, use of eltrombopag for post-CAR T leukopenia and thrombocytopenia was considered effective in recovery of counts and prevention of bleeding in a high-risk patient population. The use of eltrombopag for post-CAR T cytopenias was considered safe without any significant toxicities of thrombosis or myelodysplasia.

Thrombotic and Bleeding Events in Japanese Adolescent and Young Adult PV and ET: Results from Japanese Multicenter Retrospective Study

[Background] There were no large-scale retrospective studies about adolescent and young adult (AYA) polycythemia vera (PV) or essential thrombocythemia (ET) in Japan. The characteristics in AYA PV or ET in Asia are not well-reported, except for one retrospective study using the Health Insurance Review and Assessment Service database in Korea. To reveal the clinical features, especially with regard to thrombotic and bleeding events in Japanese AYA PV and ET, we decided to perform secondary data analysis of Japanese multicenter large registry data, JSH-MPN-R18. [Methods] Data of PV and ET aged 20 to 39 at the initial visit were extracted from registration data in JSH-MPN-R18 as AYA cohort, and were compared to non-AYA cohort over 40 years old. Differences among categorical and continuous variables were evaluated by chi-square test or Fisher's exact test, and by Mann-Whitney U test, respectively. [Results] 31 PV (median age; 33 years［range 26-39］, male/female; 19/12) and 141 ET (median age; 32 years［range 20-39］, male/female; 52/89) were identified as AYA cohort, which represented 5.2% and 12.2% of overall PV or ET cohort, respectively. Non-AYA cohort consisted of 565 PV and 1011 ET. Regarding laboratory parameters, neutrophil ratio and counts were lower in AYA PV than in non-AYA PV, whereas, leukocyte counts, neutrophil ratio and counts, LDH and D-dimer level were lower in AYA ET than in non-AYA ET. The frequency of JAK2 V617F-mutated patients was lower in AYA than in non-AYA PV and ET (PV; 61.2% vs.77.2%, p=0.05, ET; 46.0% vs. 57.8%, p&amp;lt;0.01). Regarding the treatment, antiplatelet or anticoagulant therapy was introduced into 61.3% of AYA PV and 51.8% of AYA ET patients. Cytoreductive therapy (CRT) was provided to eight (25.8%) AYA PV and 61 (43.3%) AYA ET. In 62.5% of AYA PV and 75.4% of AYA ET, who received CRT, CRT was adopted for the reasons except for the past or recent thrombotic events (TE)/bleeding events. AYA PV patients experienced only one pulmonary embolism before diagnosis and one lacunar cerebral infarction (CI) at diagnosis. There were no TE after diagnosis in AYA PV. In terms of bleeding events, AYA PV had one event (details unknown) before diagnosis and two events (gastrointestinal bleeding and details unknown) after diagnosis. The frequency of AYA PV patients with TE had a tendency to be lower than that of non-AYA PV (6.5% vs 19.1%, p=0.09), although there were no statistical differences between the numbers of bleeding events between AYA and non-AYA PV during all of the course. AYA ET had nine TE (3 CI, 2 deep vein thrombosis (DVT), 1 transient ischemic attack (TIA), 1 peripheral arterial disease (PAD), 2 details unknown) before diagnosis, six TE (3 DVT, 2 CI, 1 TIA) at diagnosis, and six TE (1 myocardial infarction, 1 CI, 1 PAD, 1 TIA, 2 details unknown) after diagnosis. Fewer TE occurred in AYA ET than in non-AYA ET before (6.4% vs 19.8%, p&amp;lt;0.01) and at diagnosis (4.3% vs 9.5%, p=0.04). However the frequency of TE was not different (4.3% vs. 6.7%, p=0.36) after diagnosis. AYA ET had experienced only one bleeding event (oral mucosal bleeding) before diagnosis. Bleeding events were never found at or after diagnosis. Fewer bleeding events were detected in AYA ET than non-AYA ET during all of the course (0.7% vs 8.6%, p&amp;lt;0.01). The percentage of venous TE in total TE was higher in AYA-MPN than in non-AYA MPN (26.1% vs 5.4%). [Conclusion] Our analysis is the first retrospective cohort which revealed clinical features related to TE and bleeding events in Asian AYA MPN from large multicenter registry data. Lower neutrophil ratio and absolute counts at diagnosis might be attributable to lower mutated JAK2 allele burden in AYA PV, and lower frequency of JAK2-mutated ET in AYA ET. Regarding bleeding events, fewer bleeding events were found in AYA ET than in non-AYA ET. However in PV, there were no statistical differences in bleeding events between AYA and non-AYA. About TE, AYA PV and ET had fewer TE than non-AYA PV and ET. The percentage of venous TE in total TE was higher in AYA MPN than in non-AYA MPN also in Japan, but it was much lower than those reported in previous European or US cohorts, in which venous TE were more common than arterial TE. Especially after diagnosis, venous TE were never detected in either AYA PV or ET in Japan. Considering that the frequency of venous TE in the Korean receipt data was as low as that in our cohort, fewer venous TE might be one of the specific characteristics in Asian AYA MPN different from European or US AYA MPN.

Caprini Model Integration into an Electronic Medical Record to Improve Perioperative Venous Thromboembolism Prophylaxis.

This quality-improvement retrospective cohort study of patients undergoing major elective nononcologic gynecologic surgery compares the proportion of patients receiving appropriate perioperative venous thromboembolism (VTE) chemoprophylaxis before and after a novel integration of the Caprini risk-assessment model (RAM) into the electronic medical record (EMR). A sample size of 83 patients in each group (166 total) was calculated to provide 80% power and show a 20% increase in appropriate administration of VTE prophylaxis, with an alpha of 0.05. Heparin was appropriately used in 24 patients (28.9%) in the pre-Caprini-RAM group and 39 patients (47.0%) in the post-Caprini-RAM group ( P =.016). There were no differences in bleeding events, transfusions, or other secondary outcomes. Integrating the Caprini-RAM into an EMR for patients undergoing nononcologic gynecologic surgery significantly improved appropriate use of VTE chemoprophylaxis.

Comparison of Standard Versus Intermediate Prophylaxis Dose for Venous Thromboembolism Prophylaxis in Patients Hospitalized With COVID-19 Infection.

Background: COVID-19 infection is associated with a high risk of venous thromboembolism (VTE) events. VTE prophylaxis reduces the risk of these events. The optimal dose of VTE prophylaxis however remains uncertain. Objectives: To compare the incidence of VTE in patients treated with either standard dose VTE versus intermediate dose VTE prophylaxis. Methods: In this retrospective cohort study, we analyzed data from 1786 adult patients admitted into the hospital with polymerase chain reaction confirmed COVID-19 infection between April 2020 to September 2021. For analysis, patients were divided into 2 cohorts: either standard dose prophylaxis treatment group (patients who received either unfractionated heparin 5000units 3 times a day or enoxaparin 30-40 mg daily subcutaneously) or intermediate dose VTE prophylaxis group (patients received either unfractionated heparin 7500 units 3 times daily or enoxaparin 30-40 mg twice a day subcutaneously). The primary outcome was incidence of VTE events described as either deep vein thrombosis (DVT) or pulmonary embolism (PE). Secondary outcome was bleeding events. Results: During the study period, 398 (22%) patients were primarily treated with standard dose VTE prophylaxis, whereas 1388 (78%) patients were treated with intermediate dose VTE prophylaxis. There was a significantly higher incidence of venous thromboembolism events noted in the standard dose prophylaxis treatment group when compared with the intermediate dose prophylaxis group (25/398 (6.3%) vs 35/1388 (2.5%) P < .001, [Odds Ratio 2.6197, 95% confidence interval = 1.5482-4.4327]). Multivariable-adjusted logistic regression, adjusting for age, obesity, and smoking, with the intermediate dose prophylaxis treatment group as the referent category revealed higher odds for incident venous thromboembolism events in the standard dose prophylaxis group. There was no statistically significant difference in bleeding events between the 2 treatment groups (9 (2.3%) for standard dose prophylaxis group vs 46 (3.3%) for intermediate dose prophylaxis group P = .26). Conclusions: Among patients hospitalized with COVID-19 infection, patients receiving intermediate dose VTE prophylaxis experienced lower incident rates of venous thromboembolism events compared to those receiving standard dose VTE prophylaxis without a statistically significant increase in the risk of bleeding events.

Evaluation of venous thromboembolism prophylaxis protocol in hematopoietic cell transplant patients

Hematopoietic cell transplant (HCT) recipients are at risk for thromboembolic and bleeding complications. There is limited evidence regarding the optimal approach to managing venous thromboembolism (VTE) prophylaxis in hospitalized patients undergoing HCT. In this retrospective cohort study, we evaluated the incidence of bleeding and VTE events in hospitalized HCT patients who received VTE prophylaxis per our institution’s VTE Prophylaxis Protocol (VPP), with either enoxaparin 40 mg subcutaneously daily or heparin 5 000 units subcutaneously twice daily, compared to historical controls who did not receive VTE prophylaxis. The primary outcome was a composite of major bleeding events, clinically relevant non-major bleeding (CRNMB), and minor bleeding. The secondary outcome was a composite of VTE events. A total of 614 patients were evaluated, including 278 prior to and 336 after implementation of VPP. VTE prophylaxis resulted in no difference in bleeding events (15.1% in the pre-VPP group vs. 14.6% in the post-VPP group, p = 0.86) or composite of major and CRNMB events (0.72% vs. 0.30%, p = 0.59). There was a trend toward lower incidence of VTE events in the post-VPP group which did not reach statistical significance (8.6% vs. 6.0%, p = 0.20). We conclude that VTE prophylaxis does not pose additional bleeding risk in HCT patients.

Comparison of bleeding risk and hypofibrinogenemia-associated risk factors between tigecycline with cefoperazone/sulbactam therapy and other tigecycline-based combination therapies.

Background: Tigecycline and cefoperazone/sulbactam can cause coagulation disorders; tigecycline may also lead to hypofibrinogenemia, raising safety concerns. This study aimed to investigate whether tigecycline plus cefoperazone/sulbactam increases the risk of bleeding compared with other tigecycline-based combination therapies and identify risk factors for tigecycline-associated hypofibrinogenemia. Methods: In this multi-method, multicenter, retrospective study, coagulation and other baseline variables were compared using a cohort study, and risk factors for hypofibrinogenemia using a case-control study. Results: The 451 enrolled participants were divided into three group: tigecycline plus cefoperazone/sulbactam (Group A, 193 patients), tigecycline plus carbapenems (Group B, 200 patients) and tigecycline plus β-lactams without N-methylthio-tetrazole (NMTT) side chains (Group C, 58 patients). Activated partial thromboplastin time and prothrombin time were prolonged, and fibrinogen declined for all patients after tigecycline-based medication (all p < 0.05). Prothrombin time in Group B was significantly longer than in other groups (p < 0.05), but there were no significant differences in bleeding events between the three groups (p = 0.845). Age greater than 80 years (OR: 2.85, 95% CI: 1.07-7.60), treatment duration (OR: 1.29, 95% CI: 1.19-1.41), daily dose (OR: 2.6, 95% CI: 1.29-5.25), total bilirubin (OR: 1.01, 95% CI: 1.01-1.02) and basal fibrinogen (OR: 1.32, 95% CI: 1.14-1.63) were independent risk factors of hypofibrinogenemia. The optimal cut-off for treatment course was 6 days for high-dose and 11days for low-dose. Conclusion: Tigecycline plus cefoperazone/sulbactam did not increase the risk of bleeding compared with tigecycline plus carbapenem, or tigecycline plus β-lactam antibiotics without NMTT-side-chains. Coagulation function should be closely monitored in patients receiving tigecycline treatment.

Unfractionated heparin or low-molecular-weight heparin for venous thromboembolism prophylaxis after hepatic resection: A meta-analysis.

Two systematic reviews summarized the efficacy and safety of pharmacological prophylaxis for venous thromboembolism (VTE) after hepatic resection, but both lacked a discussion of the differences in the pharmacological prophylaxis of VTE in different ethnicities. Therefore, we aimed to evaluate the efficacy and safety of low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) for VTE prophylaxis in Asian and Caucasian patients who have undergone hepatic resection. We searched PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data, and VIP databases for studies reporting the primary outcomes of VTE incidence, bleeding events, and all-cause mortality from January 2000 to July 2022. Ten studies involving 4318 participants who had undergone hepatic resection were included: 6 in Asians and 4 in Caucasians. A significant difference in VTE incidence was observed between the experimental and control groups (odds ratio [OR] = 0.39, 95% confidence interval [CI]: 0.20, 0.74, P = .004). No significant difference in bleeding events and all-cause mortality was observed (OR = 1.29, 95% CI: 0.80, 2.09, P = .30; OR = 0.71, 95% CI: 0.36, 1.42, P = .33, respectively). Subgroup analyses stratified by ethnicity showed a significant difference in the incidence of VTE in Asians (OR = 0.16, 95% CI: 0.06, 0.39, P < .0001), but not in Caucasians (OR = 0.69, 95% CI: 0.39, 1.23, P = .21). No significant differences in bleeding events were found between Asians (OR = 1.60, 95% CI: 0.48, 5.37, P = .45) and Caucasians (OR = 1.11, 95% CI: 0.58, 2.12, P = .75). The sensitivity analysis showed that Ejaz's study was the main source of heterogeneity, and when Ejaz's study was excluded, a significant difference in VTE incidence was found in Caucasians (OR = 0.58, 95% CI: 0.36, 0.93, P = .02). This study's findings indicate that the application of UFH or LMWH for VTE prophylaxis after hepatic resection is efficacious and safe in Asians and Caucasians. It is necessary for Asians to receive drug prophylaxis for VTE after hepatic resection. This study can provide a reference for the development of guidelines in the future, especially regarding the pharmacological prevention of VTE in different ethnicities.

Abstract 12411: Validation of Academic Research Consortium for High Bleeding Risk (ARC-HBR) Definition in East-Asian Patients

Introduction: Clinical applicability of the Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria in East-Asian patients receiving potent antiplatelet therapy for acute coronary syndromes (ACS) is still undetermined Methods: Using individual patient data from the TICAKOREA trial, which is a multicenter trial randomly compared ticagrelor and clopidogrel in Korean patients with ACS, we determined the prognostic effect of ARC-HBR criteria on bleeding and ischemic events. The primary safety outcome was bleeding of academic research consortium (BARC) type 3 or 5 and primary efficacy outcome was major adverse cardiovascular events (MACE; a composite of cardiovascular death, myocardial infarction, or stroke). Results: HBR patients compared with non-HBR patients had a higher incidence of BARC type 3 or 5 bleeding (10.0% vs. 3.61%; hazard ratio [HR], 2.98; 95% confidence interval [CI], 1.52 to 5.86) and MACE (14.3% vs. 6.1%; HR 2.35; 95% CI, 1.35-4.10). Among HBR patients, there was no significant difference in bleeding events between ticagrelor and clopidogrel (10.2% vs. 9.8%; HR 1.15; 95% CI, 0.38-3.44). However, the efficacy endpoint of MACE tended to be higher in the ticagrelor group than in the clopidogrel group (19.1% vs. 8.1%; HR 2.31; 95% CI, 0.91-5.83) Conclusions: In Korean patients with ACS intended to receive early invasive management, ARC-HBR criteria is sufficiently applicable to predict both bleeding and ischemic risk. We also observed differential safety and effectiveness of ticagrelor compared with clopidogrel according to presence or absence of ARC-HBR criteria.

Dengzhan Shengmai capsule versus Aspirin in the treatment of carotid atherosclerotic plaque: A single-centre, non-inferiority, prospective, randomised controlled trial

BackgroundAspirin is an effective antiplatelet agent for the treatment of carotid atherosclerosis. However, the high risk of bleeding events associated with the drug makes it necessary to seek a safer alternative, with similar or more efficacy than aspirin. Dengzhan Shengmai (DZSM) capsules have been widely used to treat carotid atherosclerosis, and if proven to be non-inferior to aspirin, it may be preferable over the latter for carotid atherosclerosis treatment due to its numerous advantages. We conducted a randomised trial to test the non-inferiority of DZSM to aspirin for the treatment of carotid atherosclerotic plaques. MethodsWe performed a single-centre, prospective, open-label, randomised non-inferiority trial. Patients with carotid atherosclerotic plaques were enrolled and randomly assigned (1:1) to receive either DZSM capsules or aspirin. The follow-up period was 12 months. The primary outcome was the mean change in carotid intima-media thickness (IMT). Secondary outcomes included ischaemic events, rate of lumen stenosis, lipid levels, and plaque scores, length, counts, and vulnerability. Adverse events and laboratory test results were recorded as safety outcomes. The non-inferiority of DZSM was demonstrated when the lower limit of the one-sided 97.5% confidence interval (CI) of the difference in IMT between groups was more than -0.06 mm (margin of non-inferiority). This trial has been registered at ClinicalTrials.gov (CHiCTR1900021365). ResultsFrom 1 April 2019 to 30 September 2019, 150 patients were enrolled, and there was no statistical difference in demographics between the groups. Intention-to-treat analysis showed that the decrease in IMT(∆IMT) was 0.216 ± 0.160 and 0.225 ± 0.149 mm in the DZSM and aspirin groups, respectively. The one-sided 97.5% CI for the difference between ∆IMTs was (-0.0593, +∞). The non-inferiority of DZSM was demonstrated (Pnon-inferiority = 0.0234). There was no significant difference in the incidence of ischaemic events between the groups (P = 1.0). The DZSM group had significantly reduced plaque scores (P < 0.0001), length (P < 0.0001), and counts (P < 0.0001), and improved plaque vulnerability (P < 0.0001). The DZSM group also had reduced levels of low-density lipoprotein cholesterol (LDL-C) (P < 0.0001). Finally, the DZSM group had a lower incidence of total adverse events (14.7% vs. 28%, P = 0.046), especially gastrointestinal discomfort (5.3% vs. 16%, P = 0.034). Although there was no significant difference in bleeding events (0 vs. 5.3%, P = 0.120), the DZSM group tended to have a lower incidence. ConclusionThis trial demonstrated that DZSM was not inferior, in efficacy, to aspirin in treating carotid atherosclerotic plaques, and was found to be superior to aspirin in terms of safety. This study provides a new approach for treating carotid plaques, especially in aspirin-intolerant patients.

Outcome of transcatheter aortic valve replacement in patients over 85years of age versus patients aged85 and younger.

IntroductionThe Dutch general population is aging rapidly. Many of these patient are fit and eligible for TAVR. However, studies on outcome in older versus younger patients are scant.Material and methodsA single-centre retrospective study comparing patients older and younger than age 85 on outcome.Results190 patients underwent TAVR: 136 were aged 85 or younger (U85), 54 were older than 85 (O85). The U85 group had more men (U85: 71 [52.2%] vs O85: 19 [35.2%]; p = 0.034), a higher incidence of diabetes (U85: 36 [26.5%] vs O85: 3 [5.6%]; p = 0.001) and atrial fibrillation (U85: 35 [25.7%] vs O85: 5 [9.3%]; p = 0.03) and a higher body mass index (U85: 27.5 [± 5.24] vs O85: 26 [± 3.78]; p = 0.027). In the O85 group there was a lower estimated glomerular filtration rate (O85: 50.28 [± 15.32] ml/min vs U85: 65.25 [± 29.97] ml/min; p = 0.012). There was no difference in 30-day mortality (U85: 6 [4.4%] vs O85: 3 [5.6%]) and 1‑year mortality (U85 9 [6.6%] vs O85 3 [5.6%]) (p = 0.521). There was an equal amount of new onset permanent left bundle branch block (U85: 38 [27.9%] vs O85: 14 [25.9%]; p = 0.896) and permanent pacemaker implantation (U85: 28 [20.6%] vs O85: 28 [20.6%]; p = 0.748). There was no difference in bleeding events (p = 0.469), vascular complications (p = 0.195) or moderate/severe regurgitation (p = 0.972). The U85 group had a slightly longer admission duration (U85 6.29 [± 5.289] days vs O85 5.98 [± 3.328] days (p = 0.037)).ConclusionTAVR in patients over 85 years of age has excellent outcome, comparable to those aged 85 and younger.

Associated factors and safety of the rapidly achieving first therapeutic target of warfarin in hospitalized patients: a retrospective cohort study.

Warfarin is a commonly used anticoagulant drug in clinical practice. Rapidly achieving the first therapeutic international normalized ratio (INR) of warfarin may reduce the hospital length of stay. However, little research has been carried out to evaluate the influencing factors and the safety of rapidly achieving the first therapeutic INR target of warfarin. To investigate the associated factors and the safety of rapidly achieving the first therapeutic INR target of warfarin. A retrospective cohort study was conducted in inpatients who took warfarin from November 2018 to October 2019. Patients' information was retrieved from medical records. 487 patients were included. The mean achieving first therapeutic target time was 6.0 ± 3.2 days (median, 5.0 days). Age > 65 years, body mass index < 24kg/m2, and initial warfarin dose ≥ 3mg/d were independent factors associated with the rapidly achieving first INR target of warfarin therapy. The incidence of INR ≥ 4 was higher in patients achieving the first INR target rapidly than those achieving the first INR target slowly, while there were no significant differences in bleeding events between the two groups. Hospitalized patients aged > 65 years, with a body mass index < 24kg/m2, or receiving an initial warfarin dose ≥ 3mg/d were more likely to achieve the first INR target of warfarin rapidly. Closer INR monitoring and appropriate warfarin dose adjustment are recommended to improve the safety for patients achieving the first INR ≥ 1.8 within 6 days after beginning oral warfarin.

Prophylactic Rivaroxaban Therapy forLeft Ventricular Thrombus After Anterior ST-Segment Elevation Myocardial Infarction.

The aim of this study was to investigate the effects of rivaroxaban on left ventricle thromboprophylaxis in patients with anterior ST-segment elevation myocardial infarction (STEMI). Anterior STEMI is associated with an increased risk of left ventricular thrombus (LVT) formation. The contemporary role of prophylactic rivaroxaban therapy remains unclear. We randomly assigned 279 patients with anterior STEMI who had undergone primary percutaneous coronary intervention to receive, in a 1:1 ratio, low-dose rivaroxaban (2.5mg twice daily for 30days) and dual antiplatelet therapy (DAPT) or only DAPT. The primary efficacy outcome was the LVT formation within 30days. Net clinical adverse events were assessed at 30days and 180days, including all-cause mortality, LVT, systemic embolism, rehospitalization for cardiovascular events, and bleeding. The addition of low-dose rivaroxaban to DAPT reduced LVT formation within 30days compared with only DAPT (0.7% vs 8.6%; HR: 0.08; 95%CI: 0.01-0.62; P=0.015; P< 0.001 for superiority). Net clinical adverse events were lower within 30days in the rivaroxaban group versus those in the only DAPT group and remained relatively low throughout the follow-up period. There were no significant differences in bleeding events between the 2 groups in 30days and 180days. However, 1 case of intracranial hemorrhage (major bleeding) occurred in the rivaroxaban group within 30days. Our results supported that the short-duration addition of low-dose rivaroxaban to DAPT could prevent LVT formation in patients with anterior STEMI following primary percutaneous coronary intervention. A larger multiple-institution study is necessary to determine the generalizability.

Non-synonymous alterations in AKR7A3 and ABCA6 correlate with bleeding in aged patients treated with rivaroxaban.

Rivaroxaban is an oral anticoagulant that inhibits thrombin and blocks coagulation cascade through directly inactivating factors Xa. Despite rivaroxaban is widely used for prevention and treatment of venous thrombosis, and its common adverse reactions have been reported, including abnormal coagulation, mucosal hemorrhage, hematuria, and intracranial hemorrhage. To explore potential drivers of individual differences in adverse reactions induced by rivaroxaban, we performed whole‐exome sequencing and found that AKR7A3 rs1738023/rs1738025 and ABCA6 rs7212506 are susceptible sites for rivaroxaban‐related bleeding in aged patients treated with rivaroxaban. Gene functional annotation and signaling pathway enrichment indicated that homozygous mutations in AKR7A3 and ABCA6 might alter normal rivaroxaban transport and metabolism, and lead to continuous accumulation of activated drugs and toxic substances in vivo. Our results suggested that interindividual differences in bleeding events induced by rivaroxaban may be potentially driven by genetic alterations related to abnormal metabolism and transport of rivaroxaban.

Safety of Direct Acting Oral Anticoagulants (DOACs) in Comparison to Low Molecular Weight Heparin (LWMH) in Gastrointestinal and Genito-Urinary Cancers

Introduction:DOACs are absorbed in the gastrointestinal (GI) tract and DOAC elimination is primarily through the GI and genitourinary (GU) systems. The safety of DOACs in cancer associated thrombosis in subjects with malignant lesions in GI and GU malignancies has been of concern. Studies have been sparse and data conflicting.Methods:We identified patients with active GI and GU malignancies from July 2001 to July 2020 with confirmed VTE at our institution. Patients who received either enoxaparin or a DOAC (apixaban or rivaroxaban) were included in the study. Demographic, disease characteristics, VTE data and events were extracted from electronic medical records (EMR). Date of anticoagulation (AC) initiation was based on the first order and/or prescription of the anticoagulant. Patients were followed either to the earliest bleeding event (BE) or one year from initiation, whichever occurred first. BEs were categorized based on ISTH guidelines. Variables were compared between LMWH and DOAC cohorts, as well as between the apixaban and rivaroxaban cohorts, using t-tests for continuous variables and chi-squared tests or Fisher's exact test for categorical variables.Results:We identified a total of 206 patients, 159 in the DOAC and 47 in the LWMH groups. Table 1 describes the baseline characteristics of the study populations. Median age of patients, gender and BMI were comparable for all groups. When evaluated for type of cancer, 66.6% of patients had active GI malignancy while 33.3% had active GU tumors. The majority of the patients given DOACs had a better ECOG status than those in the LMWH group (p=0.0023), but no difference was noted for ECOG status between DOACs (p=0.69). Most patients had metastatic disease. The majority of the VTE events were in the form of DVTs. Concomitant aspirin intake was 9.4% in DOAC and 4.2% in LMWH groups. Cancer subtypes and AC choice data are given in detail in Table 2.LMWH use was higher in blacks and somewhat lower in the Hispanic population (Table 1). When anticoagulation choice was examined by primary tumor site (Table 2), disproportionately more patients with GU tumors were placed on LMWH while more GI cancers were given a DOAC (p=0.014). Extent and stage of the cancer did not appear to bias anticoagulant choice (p=0.62). Within the DOACs, rivaroxaban use was higher in the GI cancers but considerably less used in the GU malignancies (p=0.00049).There was one recurrent thrombosis in each of the apixaban (1/86) and the rivaroxaban (1/73) cohorts. There were no recurrent events in the LMWH (0/47) cohort.The majority of patients in the DOAC and LMWH groups, 88.1% and 86.4%, had no CRNMB or major bleeding events in the 1-year period after the initiation of the therapeutic AC (Table 3). Combined BE (clinically relevant non-major bleeding [CRNMB] and major bleeding rates) with apixaban, rivaroxaban and LMWH were 17.4% (15/86), 20.5% (15/73), and 19.1% (9/47) respectively. There were no fatal bleeding episodes in any of the groups. Most of the bleeding events on DOACs and LMWHs occurred in the same organ system as the primary cancer (Table 3) but there was no statistically significant difference in bleeding events between patients on DOACs or LMWH for GI, GU or all cancer types (p=0.63, 0.75 and 0.97 respectively). Within DOACs, we also noted no statistically significant difference in the bleeding events with apixaban as compared to rivaroxaban in patients with GI primary, GU primary or all cancer types together, (p=0.47, 0.94 and 0.62 respectively).Conclusion:No significant differences in major/CRNM bleeding events were found for patients with GI or GU cancer associated thrombosis given DOACs (apixaban/rivaroxaban) vs enoxaparin. The tumor site is often the site of bleeding, but no differences in tumor-specific site bleeding could be shown by anticoagulant choice. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

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.