Significant Difference In Bleeding Events Research Articles

Antithrombotic therapy in patients with atrial fibrillation after myocardial infarction and percutaneous coronary intervention

Abstract Background Antithrombotic treatment with oral anticoagulants is recommended in clinical practice guidelines for patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) and concurrent atrial fibrillation (AF). Previous randomized controlled trials comparing warfarin and DOAC have primarily focused on bleeding complications. Consequently, the benefits and risks in an all-comer population remain uncertain. Purpose This study aimed to evaluate adherence to clinical practice guidelines within a large nationwide cohort and to compare outcomes among patients with MI and AF who were treated with dual antiplatelet therapy (DAPT), Warfarin, or DOAC. Method We utilized data from the nationwide SWEDEHEART registry to identify all patients with MI and AF between January 2010 and January 2021. We included all patients who underwent PCI and had a CHA2DS2-VASC score of ≥2 for men and ≥3 for women. The follow-up was one year. Patients were allocated into one of three antithrombotic treatment groups based on discharge medications: (1) Warfarin-based, (2) DOAC-based, and (3) DAPT only. The warfarin- and DOAC-based groups comprised patients on either dual or triple antithrombotic therapy. Study outcomes included: (1) major adverse cardiovascular events (MACE), defined as a composite of all-cause death, MI, or stroke; (2) net adverse cardiovascular events (NACE), which included MACE and bleeding complications; and (3) the individual components of MACE and NACE. Cox regression models were used to adjust for differences in baseline characteristics. Results Mean age among the 12,321 patients included was 76.1 years. At discharge, 3,563 (29%) were treated with warfarin, 3,671 (30%) received DOAC treatment, and 5,087 (41%) with DAPT alone. The percentage of patients treated with OAC increased from 30% in 2010 to 84% in 2021. Warfarin- and DOAC-based strategies were associated with lower MACE compared to DAPT alone, with adjusted hazard ratios [HR] (95% CI) of 0.77 (0.69-0.97) and 0.78 (0.69-0.90), respectively, as well as lower rates of NACE with adjusted [HR] (95% CI) of 0.84 (0.76-0.93) 0.84 (0.75-0.94), respectively. This difference was primarily driven by a difference in mortality, with adjusted ]HR] (95% CI) of 0.78 (0.67-0.91) and 0.80 (0.68-0.94), respectively. There were significantly fewer stroke events in the DOAC group (2.5 % vs 3.3%) compared with DAPT. No significant differences in bleeding events were observed between any of the treatment groups. Conclusions In this real-life retrospective study, we observed an increased utilization of guideline recommended OAC treatment over time. Both DOAC and warfarin treatment regimens were associated with a lower incidence of MACE and NACE compared to DAPT alone. No significant difference in outcomes were observed comparing DOAC vs Warfarin.

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.

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.

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.

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.

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.

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 Role of D-Dimer for Optimal Thromboprophylaxis Strategy in Patients with COVID-19

Background:Novel coronavirus infection (SARS CoV-2 or COVID-19) is associated with a high risk of thrombotic complications, including macro- and micro-thrombi in major organs, leading to increased morbidity and mortality. Anticoagulant use, mainly heparin, which has both anticoagulant and anti-inflammatory properties, has been suggested as potentially beneficial. However, the optimal dose of anticoagulant for patients with COVID-19 is unknown. Establishing the optimal thromboprophylaxis strategy and determining the role of biomarkers for patient risk stratification may help to improve outcomes in COVID-19.Methods:This single-center retrospective cohort study is part of an ongoing Quality Improvement project on the use of an anti-factor Xa-driven heparin protocol, which includes a low-dose intravenous (IV) unfractionated heparin (UFH) option, being conducted at our medical center. Data on the type, dose, and indication for anticoagulation as well as outcomes including thrombosis, bleeding and survival was collected for inpatients diagnosed with COVID-19 between mid-March and June 15, 2020. To address COVID-coagulopathy we developed a d-dimer-based anticoagulation protocol for patients with COVID-19 (Figure 1). We recorded anticoagulant use as either standard prophylactic, escalated prophylactic (low-dose intravenous unfractionated heparin titrated to achieve an anti-factor Xa level of 0.1-0.3 anti-Xa units or enoxaparin 0.5mg/kg subcutaneously every 12 hours) or standard therapeutic dose used during the hospitalization. The primary endpoints assessed were ISTH-defined major and clinically relevant non-major bleeding (CRNMB) events and survival. Secondary endpoints included incidence of breakthrough thrombosis and duration of hospitalization.Results:A total of 263 patients with COVID-19 were reviewed. Of these, 68.44% of patients received prophylactic, 12.55% escalated prophylactic and 19.01% therapeutic dosage. Of total, 129 (49%) were receiving ICU level of care. No major bleeding events were observed. The incidence of CRNMB was 4.56% in the whole cohort, which did not differ significantly between the escalated prophylactic and therapeutic groups (12% and 12.12%, respectively). Patients treated with standard prophylaxis had less CRNMB (1.11%), but this was not statistically significant in a multivariate analysis that included other confounding factors such as age, sex, ethnicity, BMI, comorbidity, HASBLED bleeding risk, and sepsis induced coagulopathy score (SICS).The mortality rate was 12.6% in the whole cohort (7.22%, 21.21% and 26% in prophylactic, escalated prophylactic, and therapeutic dosage, respectively). Factors significantly associated with increased mortality included age and ICU level of care (HR 1.10, 95%CI [1.05, 1.15] and HR 20.42, 95%CI [2.84, 146.72], respectively). The use of therapeutic dose heparin and high-flow nasal cannula demonstrate a survival benefit in multivariate analysis (HR 0.13, 95%CI [0.04,0.44] and HR 0.23, 95%CI [0.07, 0.72], respectively; Figure 2).Breakthrough thrombosis occurred in 7 (2.66%) patients; 1 (0.56%), 1 (3.03%) and 5 (10%)) in prophylactic, escalated prophylactic and therapeutic dosage, respectively but very few diagnostic tests were performed during this time period. Duration of hospitalization was significantly longer in the therapeutic dose group when compared to escalated prophylaxis and standard prophylactic groups.Conclusion:In this cohort of inpatients with COVID-19, there were no major bleeding events related to any dose of heparin or LMWH prophylaxis. By multivariate analysis, implementation of a d-dimer-titrated anticoagulation strategy was not associated with increased CRNMB. Therapeutic dose heparin based on a d-dimer-driven anticoagulation protocol was associated with a survival benefit in COVID19-infected patients. Limitations of this study include the retrospective observational nature and a lack of a uniform diagnostic protocol for patients with suspected VTE. Although no significant difference in bleeding events were observed in our study subgroups, randomized clinical trials are necessary to determine optimal thromboprophylaxis strategy in the COVID-19 population.DisclosuresNo relevant conflicts of interest to declare.

Direct Oral Anticoagulants (DOACs) Vs. Low Molecular Weight Heparins (LMWH) for Venous Thromboembolism (VTE) in Patients with Primary Brain Tumors or Secondary Brain Metastases

Background: Management of venous thromboembolism (VTE) in patients with central nervous system (CNS) malignancies is challenging as there is an increased risk of recurrent VTE and intracranial hemorrhage (ICH). Low molecular weight heparins (LMWH) have historically been the standard of care for treatment of cancer-associated thrombosis (CAT). Current guidelines recommend direct oral anticoagulants (DOACs) for CAT treatment, but patients with CNS malignancies have limited representation in the supporting clinical trials. This multicenter, retrospective cohort study evaluated the safety and efficacy of DOACs compared to LMWH for CAT in patients with primary brain tumors or secondary brain metastases. Patients/Methods: In this multicenter, retrospective cohort study, adult patients with a diagnosis of primary brain tumor or secondary brain metastases who received either a DOAC or LMWH for CAT were evaluated. The primary outcome was the incidence of any bleeding event within a 6-month period following the initiation of anticoagulation. Secondary outcomes included incidence of recurrent VTE events, major bleeding, clinically relevant non-major bleeding (CRNMB), and minor bleeding, within a 6-month period following the initiation of anticoagulation. Patients were excluded if their indication for anticoagulation was stroke, non-cancer-associated VTE, or VTE prophylaxis, were on LMWH for one week or less while bridging to warfarin, or received a diagnosis of VTE at an outside hospital. All bleeding events were defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. Primary and secondary outcomes were analyzed using Fisher's exact test for categorical variables and Wilcoxon rank-sum tests for non-parametric continuous variables. Results: Between January 1, 2012 to October 9, 2019, one-hundred eleven patients met inclusion criteria. Of the patients who met inclusion criteria, 26 (23.4%) patients had primary brain tumors and 85 (76.6%) patients had secondary brain metastases. Bleeding events occurred in 7 of 55 patients (12.7%) in the DOAC group compared to 13 of 56 (23.2%) patients in the LMWH group (RR 0.55, 95% CI 0.24-1.27). Recurrent VTE events occurred in 3 of 55 (5.5%) patients in the DOAC group compared to 3 of 56 (5.4%) patients in the LMWH group (RR 1.02, 95% CI 0.21-4.83). Major bleeding occurred in 3 of 55 (5.5%) patients in the DOAC group, compared to 4 of 56 (7.1%) patients in the LMWH group (RR 0.76, 95% CI 0.18-3.26). There were no differences in the rates of CRNMB and rates of minor bleeding between groups. Conclusion: In this multicenter retrospective cohort study, therapeutic anticoagulation with DOACs showed no significant difference in bleeding events or recurrent VTE events when compared to LMWH, in patients with primary brain tumors or secondary brain metastases. We conclude that DOACs may be potentially safe and efficacious for VTE treatment in patients with primary brain tumors or secondary brain metastases. As prescribing practices are expected to continue to shift towards DOACs, this study provides preliminary evidence of the safety of DOACs in this high-bleeding risk patient population. Disclosures No relevant conflicts of interest to declare.

Issue Highlights

Issue Highlights

Thromboembolic, bleeding, and mortality risks among patients with nonvalvular atrial fibrillation treated with dual antiplatelet therapy versus oral anticoagulants: A population-based study

Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel is used for stroke prevention in patients with atrial fibrillation (AF) who refuse to take use oral anticoagulants (OACs). However, clinical data comparing these treatments are limited. The purpose of this study was to compare the clinical outcomes between DAPT and OAC in patients with AF. A cohort study using a population-wide database of the Hong Kong Hospital Authority was performed. New patients with AF from 2010-2014 who were prescribed DAPT or OAC (warfarin or dabigatran) were followed until July 31, 2016. Outcomes were thromboembolism, bleeding, and death. Propensity score (PS) matching at a ratio of 1:2 was used to select DAPT users with characteristics similar to those of OAC users, analyzed using Poisson regression. Among 51,946 new patients with AF, 8520 users of OAC and DAPT were identified. The likelihood of receiving DAPT over OAC increased with older age and previous intracranial hemorrhage. Among DAPT users, the incidences of thromboembolism, death, and bleeding per 100 patient-years were 15.8, 17.6, and 5.1, respectively. Compared to DAPT users, PS-matched analysis indicated a lower incidence of thromboembolism and/or death among OAC users (dabigatran: incidence rate ratio [IRR] 0.32; 95% confidence interval [CI] 0.19-0.55; warfarin: IRR 0.58; 95% CI 0.36-0.95), with no significant differences in bleeding events. DAPT users were at markedly increased risk for thromboembolism and death compared to OAC users. These findings indicate the need for improved stroke risk reduction strategies among patients taking DAPT and the opportunities for using OAC in high-risk groups to prevent additional events.

Cephalic vs. subclavian lead implantation in cardiac implantable electronic devices: a systematic review and meta-analysis.

Cephalic vein cutdown (CVC) and subclavian puncture (SP) are widely used techniques for lead insertion of cardiac implantable electronic devices (CIEDs). Whether one technique is superior to the other, is still being debated. The purpose of this study was to compare CVC vs. SP for lead implantation in CIEDs with respect to the incidence of pneumothorax, lead failure, and bleeding. We performed a systematic search of the pertinent literature on lead implantation in CIEDs via PubMed and Cochrane databases published over the last 25 years. Standard meta-analytic methods were applied to compare incidences of outcomes of interest. Sensitivity analysis was conducted to determine the impact of each study on the overall effect size. Risk of publication bias was assessed. A total of 20 studies were included in the analysis. These studies comprised more than 30000 patients with more than 50000 leads implanted via CVC or SP. The incidence of pneumothorax was lower with the CVC technique (n = 29/15065, 0.19% vs. n = 205/15824, 1.30%) [odds ratio (OR) 0.21, 95% confidence interval (CI) 0.10-0.42, P < 0.001]. With respect to overall lead failure, CVC was associated with better outcomes as compared to SP (n = 10/2002, 0.50% vs. n = 40/2080, 1.92%) (OR 0.25, 95% CI 0.13-0.51, P < 0.001). There was no significant difference in bleeding events (n = 25/811, 3.08% vs. n = 20/2136, 0.94%) (OR 1.69, 95% CI 0.37-7.79, P = 0.50). This comprehensive meta-analysis demonstrates lower risk for pneumothorax and lead failure associated with CVC as compared to SP. Cephalic vein cutdown should constitute the preferred venous access.

Association between D-dimer levels and clinical events in patients with mechanical heart valve replacement under oral anticoagulation therapy

Objective: To investigate the association between D-dimer levels and clinical events in patients with mechanical heart valve replacement under oral anticoagulation therapy. Methods: This prospective study included 640 consecutive patients underwent mechanical heart valve replacement in Wuhan Asia Heart Hospital between January 2013 and June 2014.Patients were assigned to abnormal D-dimer group (D-dimer level>cut off value, n=88) and normal D-dimer group (D-dimer level≤cut off value, n=552) according to D-dimer levels measured at 3 months after the initiation of oral anticoagulation therapy.All patients were followed up for 24 months or until the observation of the end points, which included thrombotic events, bleeding events and all-cause deaths.The anticoagulation therapy was monitored once per 1-2 months by the international normalized ratio (INR), and the target value was 1.8-3.0. Results: During a follow-up period of 24 months, rates of total clinical events (19.30%(17/88) vs. 5.8%(32/552), P<0.01), thrombotic events (11.4%(10/88) vs. 2.3%(13/552), P<0.01), and all-cause deaths (8.0%(7/88) vs. 2.0%(11/552), P<0.01) were all significantly higher in abnormal D-dimer group than in normal D-dimer group.There were no significant difference in bleeding events between the two groups (2.3%(2/88) vs. 3.1%(17/552), P=0.77). Multivariate Cox regression analysis showed that high D-dimer level was an independent risk factor of total clinical events (HR=3.86, 95%CI 1.92-7.76, P<0.01), thrombotic events(HR=5.29, 95%CI 2.12-13.10, P<0.01), and all-cause deaths(HR=5.32, 95%CI 1.71-16.60, P<0.01), but which was not correlated with bleeding events(HR=1.36, 95%CI 0.27-6.84, P=0.71). Conclusion: Elevated D-dimer levels are linked with clinical events in patients with mechanical heart valve replacement under oral anticoagulation therapy.