Total Bleeding Research Articles

Ticagrelor Aspirin vs Clopidogrel Aspirin in CYP2C19 Loss-of-Function Carriers With Minor Stroke or TIA Stratified by Risk Profile.

Genotype data of the Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) trial showed that efficacy of clopidogrel aspirin depended on CYP2C19 genotype and risk profile. A stratification of patients who carried CYP2C19 loss-of-function (LOF) alleles according to the risk of recurrent stroke may be important for selecting optimal antiplatelet therapy. We aimed to compare the efficacy and safety of ticagrelor aspirin with clopidogrel aspirin in CYP2C19 LOF carriers with minor stroke or transient ischemic attack (TIA) stratified by risk profile. Data were obtained from Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial. Low-risk and high-risk profiles were defined by Essen Stroke Risk Score (ESRS) (<3 [low risk] and ≥3 [high risk], respectively). A total of 6,412 CYP2C19 LOF carriers were enrolled; ticagrelor aspirin was associated with a reduced risk of primary outcome (new stroke within 90-day follow-up) in patients at low risk (hazard ratio [HR], 0.65; 95% CI, 0.48-0.82), but not in those at high risk (HR, 0.97; 95% CI, 0.73-1.29), compared with clopidogrel aspirin (p = 0.02 for interaction). Secondary outcomes generally went in the same direction as the primary outcome. The primary safety outcome of severe or moderate bleeding did not differ based on risk profile (p = 0.24 for interaction), although the incidence of total bleeding was greater with ticagrelor aspirin than with clopidogrel aspirin among patients at low risk (p < 0.01 for interaction). Analysis in the per-protocol population yielded similar results. This post hoc analysis of CHANCE-2 trial showed that CYP2C19 LOF carriers with minor stroke or TIA at low risk of recurrent stroke received a greater benefit from ticagrelor aspirin than from clopidogrel aspirin. This study provides Class II evidence that CYP2C19 LOF carriers with minor stroke or TIA at low risk, but not at high risk, of recurrent stroke (by the ESRS) received a greater benefit from ticagrelor aspirin than from clopidogrel aspirin. URL: www. gov. Unique identifier: NCT04078737.

997 ACUTE AND LATE GASTROINTESTINAL BLEEDING EVENTS AFTER LEFT VENTRICULAR MECHANICAL SUPPORT IMPLANTATION: THE ISMETT REGISTRY

Abstract Background The number of patients with end stage heart failure (HF) which requires a ventricular assist devices (VADs) implantation is constantly increasing. Gastrointestinal bleeding (GIB) represents one of the most common complications that occur in this patient population. GIB risk assessment could have important implications for candidate selection and postimplant therapeutic strategies. A recent model, called UTAH bleeding risk score (UBRS), was created with the aim of predicting the risk of GIB during LVAD support, but its use does not yet have a worldwide validation. The two most popular bleeding risk (BR) scores available, the ARC-HBR and the HAS-BLED scores, have been validated respectively in the setting of percutaneous coronary intervention and atrial fibrillation but their use in VAD patients is limited. Aims to describe clinical outcome and gastrointestinal bleeding complications of patients underwent LVAD implantation at a single tertiary referral hospital for heart transplant. Furthermore, to explore possible correlation among clinical, echocardiographic, hemodynamic parameters and the development of gastrointestinal bleeding complications has been evaluated. Finally, to evaluate the predictive value of UBRS, ARC-HBR and HAS-BLED scores in this population and to propose possible new parameters capable of predicting the risk of GIB in VAD patients. Methods Between November 2010 and December 2021, 75 consecutive patients with end stage heart failure who underwent LVAD implantation have been enrolled in this monocentric retrospective registry. Univariable and multivariable Cox regression analysis were performed to identify factors independently associated with GI bleeding in the study population. Results Patient's mean age was 57,8 ± 8,8 years. Thirty-six patients (48%) died at mean time of 579 ± 481 days after implant of VAD. The overall patient survival was 66,6% at two years. To the mean follow-up time of 737 ± 593 days, a total of 44 bleeding (incidence of 58,7%) occurred in 30 patients. Nineteen patients (25%) experienced 21 GIB events. Mean time to first GIB was 469 ± 520 days and only one event occurred within 30 days.The patient survival at two years did not differ significantly between patients who experienced GIB and those who did not (58% vs 69,6%; p=0,3). While, considering the total bleedings, overall mortality was significantly higher in patients who developed any bleeding event, than in those who did not bleed (67 vs 35%; p= 0,008).The clinical characteristics of patient with and without gastrointestinal bleeding were similar with regard to age, INTERMACS profile, etiology of heart failure and VAD implant indication.The subgroup analysis demonstrated that low cardiac output (P&amp;lt; 0,001), right ventricular disfunction (P=0,01) and severe mitral regurgitation (P= 0,01) were all associated with increased risk of GIB. In our population, high risk profile UBRS was shown to be related to a higher percentage of GIB, compared to patients with a low risk profile UBRS, in which patients without GIB prevailed (p&amp;lt; 0,001). Instead, ARC-HBR and HAS-BLED scores, didn't prove to be effective in predicting the GIB risk of VAD patient population. Conclusions High gastrointestinal bleeding rates associated with LVAD implantation do not impact negatively with patient survival. Total bleedings are correlated with higher mortality. Reduced cardiac output, right ventricular disfunction and severe mitral regurgitation are independent GIB risk factors. UBRS was able to stratify risk, in order to predict GIB, in the population tested, while ARC-HBR and HAS-BLED did not.

Stains therapy and the risk of all bleeding and intracranial hemorrhage: A meta-analysis of randomized controlled studies.

Statins had been used as a cornerstone in the primary and secondary prevention of cardiovascular disease. Widespread attention had been given to the risk of bleeding, especially intracranial hemorrhage (ICH) in patients receiving statins therapy. This study aimed to determine whether statins treatment was associated with the risk of bleeding and ICH in randomized controlled trials (RCTs). Electronic databases were searched for studies up to September 8, 2022. Articles from RCTs were included in the meta-analysis if they reported the bleeding events associated with the treatment of statins or placebo/nonstatin treatment. The risk ratios (RR) of total bleeding and ICH were pooled from the number of patients with each outcome in the statins and control groups from the included studies. Twenty-nine studies comprising 145,929 individuals (2437 incident bleeding cases) were included in the meta-analysis. After a median follow-up duration of 3.65 years, statins treatment was not associated with the risk of all bleeding (RR=1.03, 95% CI 0.93-1.15). Furthermore, in 26 studies comprising 144,177 participants, after a median follow-up duration of 3.95 years, statins treatment was not associated with the risk of ICH (RR=1.05, 95% CI 0.84-1.31). Although in the subgroup analysis with patients with prior stroke, statins treatment showed an increased risk of ICH (RR=1.47, 95% CI 1.07-2.01), sensitivity analysis showed that the result was unstable, which may be mainly driven by the SPARCL study. Statins therapy is not associated with the risk of all bleeding and ICH. Although a mildly increased risk of ICH in patients with prior stroke is observed, which may be caused by chance finding and warrant further documentation.

Updated Results of the Alta Study, a Phase 1/2 Study of Giroctocogene Fitelparvovec (PF-07055480/SB-525) Gene Therapy in Adults with Severe Hemophilia Α

Introduction: Hemophilia A, a sex-linked (F8 gene) disorder of hemostasis, results in insufficient factor VIII (FVIII) activity. Adeno-associated virus (AAV)-mediated gene transfer enables the delivery of a modified functional F8 coding sequence to hepatocytes. This subsequently synthesizes FVIII at levels preventing unprovoked bleeding events in the absence of exogenous FVIII. We present updated results with nearly 3-year follow-up on all participants from Alta, an ongoing gene therapy study in patients with severe hemophilia A (FVIII activity <1%). Methods: The phase 1/2 Alta study (NCT03061201) is a dose-ranging study of giroctocogene fitelparvovec (PF-07055480, previously called SB-525), which is a recombinant AAV serotype 6 vector encoding a modified B-domain-deleted F8 coding sequence. Giroctocogene fitelparvovec was infused into adults aged ≥18 years with severe hemophilia A in 4 cohorts (n=2 each) across 4 ascending doses: 9e11, 2e12, 1e13, and 3e13 vg/kg. The 3e13-vg/kg dose cohort was expanded with 3 additional participants. Key endpoints included safety, circulating FVIII activity, use of FVIII replacement therapy, and frequency of bleeding events. We present data with nearly 3 years of follow-up (data cutoff date: May 20, 2022). Results: Eleven male patients participated in the study (mean [SD] age, 30.3 [7.8] years; White, 81.8%). As of the cutoff date, participants had been followed for 147 to 247 weeks and 2 had not completed 3 years (156 weeks) . The most common treatment-related adverse events (AEs) reported in the highest dose cohort (3e13-vg/kg) included elevated liver enzymes and infusion-related reactions (n/N [%]): increased alanine aminotransferase (ALT; 3/5 [60.0%]), increased aspartate aminotransferase (AST; 2/5 [40.0%]), pyrexia (3/5 [60.0%]), and tachycardia (2/5 [40.0%]). Treatment-related serious AEs were reported in 1 participant (in the 3e13-vg/kg cohort) who experienced hypotension and fever with onset ≈6 h after giroctocogene fitelparvovec infusion; the events fully resolved with treatment and did not delay post-infusion discharge the next day. AEs (all causality) of ALT increases requiring ≥7 days of corticosteroids were observed in 4 of the 5 participants in the 3e13-vg/kg cohort: elevations in ALT were managed with a tapering course of corticosteroids (median duration: 56 days; range: 7-135 days), with maintenance of efficacious levels of FVIII activity, as evidenced by a lack of bleeding events around the time of corticosteroid treatment and minimal bleeding events afterwards. No participant in the 3e13-vg/kg cohort developed a confirmed inhibitor to FVIII, and there have been no thrombotic events or hepatoma detected. The three of the 5 participants in the 3e13-vg/kg cohort with available data through Week 156 had mean FVIII activity maintained in the mild to normal range (Table). Of the data available for the remaining 2 participants, 1 maintained FVIII activity levels in the mild range through Week 130 and 1 participant had FVIII activity levels below lower level of quantification (<3%) as measured with a chromogenic assay and 5.4% measured with a 1-stage assay at Week 130. In this cohort, the mean annualized total bleeding rate [(number of all bleeding episodes starting 3 weeks after study drug infusion) / (observation period in years)] was 0 for the first year postinfusion and 0.9 throughout the total duration of follow-up. In the 3e13-vg/kg cohort, 2 participants experienced an overall total of 12 bleeding events necessitating treatment with exogenous FVIII (participant 1 (n=1 event): circumstances of bleed unknown, event occurred in a target joint; participant 2 (n=11): 6 traumatic; 4 spontaneous; 1 unknown, no events occurred in a target joint). No participants in the 3e13-vg/kg cohort have resumed prophylaxis. Conclusions: A single infusion of giroctocogene fitelparvovec gene therapy in participants with severe hemophilia A remains generally well tolerated over a period of nearly 3 years postinfusion, with associated increases in FVIII levels in the moderate to normal range, without sustained AEs and with minimal overall bleeding in the highest-dose cohort (3e13 vg/kg). The ongoing phase 3 study (NCT04370054) in a larger cohort will provide more long-term data to further characterize the safety and durability of giroctocogene fitelparvovec in patients with moderately severe to severe hemophilia A. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Management of Anticoagulation and Related Outcomes in Patients with Cancer-Associated Thrombosis and Thrombocytopenia: A Systematic Review and Meta-Analysis

Background: Patients with cancer have an increased risk of venous thromboembolism (VTE) requiring anticoagulation, as well as an increased risk of thrombocytopenia due to cancer therapies or cancer itself. The optimal management of patients with VTE and thrombocytopenia is unclear. Objective: We performed a systematic review and meta-analysis to evaluate the rates of recurrent VTE and major bleeding in patients with cancer associated thrombosis and thrombocytopenia according to different anticoagulation management strategies. Methods: We searched MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials from inception to February 5, 2022. Studies assessing adult patients with cancer associated thrombosis and thrombocytopenia (platelet count < 100 x 109/L) due to malignancy or cancer therapy were included. Three main anticoagulation management strategies were reported: full dose (therapeutic dose anticoagulation +/- platelet transfusion support), modified dose (including 50% dose, prophylactic dose, or shortened duration of anticoagulation), or no anticoagulant. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding as defined by individual studies. Secondary outcomes included clinically relevant non-major bleeding, total bleeding events, and all-cause mortality. By using R software (version 4.0.3), the incidence rates of thrombotic and bleeding outcomes by anticoagulation management strategies were pooled using random effects model and expressed as events per 100 patient-months with associated 95% confidence intervals (CI). The quality of studies was assessed by ROBINS-I tool. Results: After screening 4,341 records, we included 19 studies (N=1,728 patients with platelet count < 100 x 109/L) in the systematic review, 12 of which were included in the meta-analysis (N=790) (Figure 1). There were no RCTs, two prospective cohort studies, and the rest were retrospective cohort studies. Most studies were small (N=13-471) and limited to patients with platelet count < 50 x 109/L. The majority (~90%) of patients had hematological malignancies or stem cell transplant. Low-molecular-weight heparin was the main anticoagulant reported. All studies were judged to have serious risk of bias, mainly from bias due to confounding and bias due to deviations from intended interventions. The rates of recurrent VTE, major bleeding, and total bleeding events stratified by anticoagulation management strategies (full dose, modified dose, no anticoagulation) were summarized in Table 1. The rates of recurrent VTE and bleeding complications were high regardless of the management strategies - recurrent VTE on full dose anticoagulant: 2.97 per 100 patient-months (95% confidence interval [CI] 1.86-4.75), modified dose: 7.32 per 100 patient-months (95% CI 3.59-14.94); major bleeding on full dose: 4.36 per 100 patient-months (95% CI 2.53-7.50), modified dose: 4.34 per 100 patient-months (2.30-8.20) (Table 1). There was high degree of heterogeneity in the patient population included, acuity and type of VTE, bleeding criteria used, and follow-up durations. Most studies did not account for the differences in baseline characteristics when outcomes associated with different anticoagulation strategies were reported and analyzed, which could influence the results. Conclusions: Patients with cancer associated thrombosis and thrombocytopenia have high risks of both recurrent VTE and major bleeding. Our systematic review and meta-analysis demonstrated significant heterogeneity in study conduct and reporting. Our ability to draw a firm conclusion to guide management from the current literature is severely hindered by this limitation. RCTs are needed to define the optimal care for this high-risk population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy and Safety of Personalized Prophylaxis with Simoctocog Alfa in Adult Japanese Previously Treated Patients with Severe Hemophilia a

Background: It is recommended that hemophilia A patients with a severe phenotype are treated with regular prophylaxis in order to prevent bleeds, and ideally prophylaxis should be individualized. The NuPreviq study (GENA-21) conducted in Europe showed that pharmacokinetic (PK)-guided personalized prophylaxis with simoctocog alfa (Nuwiq Esplorhem Study Design and Progress: Evaluation®) provides excellent bleeding protection, with 83% of patients having zero spontaneous bleeds during 6 months of prophylaxis. The GENA-21b study conducted also in North America and Japan further assessed personalized prophylaxis with simoctocog alfa; patients in Japan who took part on the study were also eligible to enter a long-term extension study. Aim: To assess the long-term efficacy and safety of simoctocog alfa in Japanese patients receiving personalized prophylaxis with simoctocog alfa. Methods: GENA-21b was a prospective, open-label, multicenter, phase 3b study investigating the efficacy and safety of personalized prophylaxis with simoctocog alfa in previously treated adult patients with severe hemophilia A. Male patients ≥18 years of age with severe hemophilia A (FVIII:C <1%) who have been previously treated with any FVIII products for at least 150 exposure days were eligible for this study. The study consisted of three phases: a 72-hour initial PK evaluation phase, a 1-3-month standard prophylaxis phase, and a 6-month personalized prophylaxis phase. After 6 months of personalized prophylaxis, Japanese patients were eligible to enter an optional extension phase. During the personalized prophylaxis phase, the dose and dosing interval were recommended for each patient based on their individual PK data. The primary outcome was the annualized bleeding rate (ABR) for total bleeds. Results: 58 patients were enrolled in the GENA-21b study, including 11 Japanese patients. In the 6 months prior to entering the study, all 11 Japanese patients had received FVIII prophylaxis, with a mean (SD) weekly dose 91.9 (30.9) IU/kg and a mean (SD) ABR of 7.5 (11.7). Of the patients enrolled, 56 received personalized prophylaxis, including 10 Japanese patients. The mean (SD) terminal half-life, as measured using the one-stage assay was 17.2 (4.6) h in the 10 Japanese patients compared with 15.6 (3.9) in all 56 patients. During personalized prophylaxis with simoctocog alfa, the median (interquartile range [IQR]) ABR in the Japanese patients was 3.04 (0-7.69) for total bleeds, 0 (0-5.99) for spontaneous bleeds, and 0.98 (0-5.99) for joint bleeds. 70% of Japanese patients were treated twice weekly or less while on personalized prophylaxis, with a median weekly dose that was 14% lower than during standard prophylaxis (94 vs 106 IU/kg). 9 patients entered the extension phase and remained on simoctocog alfa prophylaxis for a further 2.1 years. During the extension phase, the median (IQR) total ABR was 16% lower than during the personalized prophylaxis phase (1.76 [0-6.30] vs 2.09 [0-5.99]). The median (IQR) ABRs for spontaneous bleeds were 0.81 (0-3.36) and for joint bleeds were 0.84 (0-1.74) during the extension phase. There were no treatment-related serious adverse events, no inhibitors, and no adverse events that lead to the discontinuation of simoctocog alfa. Conclusions: Personalized prophylaxis with simoctocog alfa was efficacious in a sub-population of Japanese patients, and no treatment-related serious adverse events were reported during long-term prophylaxis. A high proportion of the patients were treated twice weekly or less. Notably, the mean ABRs decreased during long-term prophylaxis.

Abstract 11582: Implications of Glycoprotein 2b/3a Receptor Antagonist Use During Percutaneous Coronary Intervention

Introduction: Glycoprotein 2b/3a receptor antagonists (Gp 2b/3a) were once widely used during PCI. However, due to concerns for excess bleeding, the 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization downgraded their use during PCI to Class IIa. Hypothesis Higher rates of Gp 2b/3a use will be associated with higher bleeding rates, particularly in hospitals that use more femoral arterial access. Methods: We investigated the prevalence of Gp 2b/3a use during PCI among 18 PCI centers in a regional cardiac quality collaborative, between January 2017 and June 2021. Since radial access has lower bleeding rates than femoral access, we determined the impact of Gp 2b/3a use on total bleeding as defined by NCDR, stratified by access site. Results: During the study period 36,975 PCI were performed. The rate of Gp 2b/3a use among PCI centers ranged from 2.6% to 59.3% (mean ± SD 20.5% ± 18.5%). PCI centers were analyzed according to whether Gp 2b/3a use was above or below the mean frequency, and according to arterial access site preference (femoral &gt; 45% or radial &gt; 55%). Among low Gp 2b/3a use centers, centers that also favored radial access had lower bleeding rates than high femoral access centers (1.84% vs 2.43%, p=0.009). However, the bleeding risk benefit of radial access was lost in the high Gp 2b/3a usage hospitals, with bleeding rates of 4.54% in the high radial centers versus 3.41% in the high femoral centers (p&lt;0.001) (Table). Among high radial access site centers, the rate of bleeding was 2.5-fold greater in high versus low Gp 2b/3a use centers (p&lt;0.001). Conclusions: There is a wide range of Gp 2b/3a use during PCI. Above average Gp 2b/3a use increased total bleeding and neutralized the bleeding risk benefit of radial access. Further study is required to determine why bleeding rates in high radial centers were greater than high femoral centers, when Gp 2b/3a use was above average. Adherence to current guidelines for Gp 2b/3a use may reduce bleeding risk during PCI.

Performance of the Academic Research Consortium High Bleeding Risk Criteria in Patients With ST-Segment Elevation Myocardial Infarction: A Single Center Study.

We assessed the ability of predicting mortality and total in-hospital bleeding and adverse outcomes by the Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). A total of 1441 STEMI patients were recruited: HBR group 354 (25%) patients and non-HBR group of 1087 (75%) patients. A total of 131 patients (9%) had a bleeding complication during hospitalization. The bleeding complications were also categorized according to other conventional bleeding scores. According to these conventional scores, all bleeding categories were associated with HBR. In univariate logistic regression analysis, female gender, diabetes mellitus, hypertension (HT) and HBR were associated with in-hospital bleeding. However, in multivariable analysis only HT (Odds Ratio [OR] 1.528, 95% CI 1.020-2.290; P = .040) and HBR (OR 1.612, 95% CI 1.075-2.428; P = .022) independently predicted total in-hospital bleeding complications. Hospital duration was longer and mortality rate was significantly higher in patients with HBR (OR 8.755, 95% CI 5.864-13.074; P < .01). The ARC-HBR criteria may predict in-hospital bleeding events and adverse outcomes in STEMI patients undergoing pPCI.

Comparison of ticagrelor and clopidogrel on platelet function and prognosis in unstable angina

PurposeThis study aims to compare the effects of ticagrelor and clopidogrel on platelet function, cardiovascular prognosis, and bleeding in patients with unstable angina pectoris.MethodsPatients with unstable angina pectoris undergoing percutaneous coronary intervention (PCI) were enrolled (January 2018–December 2019). In total, 212 patients were treated with ticagrelor (90 mg twice daily) and 210 patients were treated with clopidogrel (75 mg once daily). Thromboelastography and light transmission aggregometry were used to measure the platelet aggregation rate (PAR). High-sensitivity troponin T (hs-TnT), pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (CRP), and heart-type fatty acid–binding protein (h-FABP) were measured to assess myocardial injury after PCI. Cardiovascular prognosis and bleeding events were evaluated in hospital and 12 months after discharge.ResultsThe PAR was significantly slower with ticagrelor (P < 0.001). hs-TnT, NT-proBNP, CRP, and h-FABP increased after compared with before PCI in both groups (P < 0.05). hs-TnT (P < 0.001) and h-FABP (P < 0.001) increased more significantly with clopidogrel. The in-hospital and 12-month major adverse cardiovascular event (MACE) rates were not significantly different between the two groups. The in-hospital total bleeding event rate was higher with ticagrelor (P < 0.05). Minor bleeding and total bleeding were more frequent at the 12-month follow-up in the ticagrelor group (P < 0.05).ConclusionTicagrelor was more effective in suppressing the PAR than clopidogrel and reduced PCI-induced myocardial injury in patients with unstable angina pectoris. However, it increased in-hospital and 12-month bleeding events and had no benefit on in-hospital and 12-month MACEs.

Utilization trends and outcomes of catheter-directed thrombolysis for pulmonary embolism in the US by race/ethnicity.

Contemporary data on catheter-directed thrombolysis (CDT) utilization trends and associated hospital outcomes in pulmonary embolism (PE) n the US is limited. Using the nationwide inpatient sample database, we identified patients hospitalized for acute PE treated with CDT from January 1, 2008, to December 31, 2018. Cochrane-Armitage test was used to evaluate the temporal trends in utilization, hospital mortality, and major bleeding rates. Multivariate logistic regression was used to compare differences in the outcomes across race/ethnicity, 4444 patients (unweighted hospitalizations) underwent CDT during the study period. The mean age ± standard deviation of the population was 58 ± 16years and the majority were males (54%). 3269 (73.6%) patients were non-Hispanic White (NHW), 802 (18.0%) patients were non-Hispanic Black (NHB), and 373 (8.4%) patients were of 'other' races/ethnicities. There was a more than tenfold increase in CDT use in 2018 compared to 2008. The total mortality and bleeding rates were approximately 7 and 10% respectively. Hospital mortality rates trended down across all races/ethnicities during the study period. A similar downward trend in bleeding rates was noted in NHB only (28.6% vs 10.7%, p = 0.04). In-hospital mortality and major bleeding odds were comparable across all races/ethnicities were comparable. NHB patients and other races were more likely to require blood transfusion and incur higher hospitalization costs compared with NHW patients. CDT use increased significantly in the US during the study period with a corresponding downward trend in in-hospital mortality across all races, and bleeding rates in NHB.

Clinical efficacy and safety of ultrasound-assisted thrombolysis vs. standard catheter-directed thrombolysis in patients with acute pulmonary embolism: A study level meta-analysis of clinical trials.

AimTo compare the clinical efficacy of ultrasound-assisted thrombolysis (USAT) vs. standard catheter-directed thrombolysis (SCDT) in patients with acute pulmonary embolism (aPE).MethodsThis study analyzed the clinical outcomes of patients with non-low-risk aPE who received USAT or SCDT. The primary outcomes were all-cause death, total bleeding, and major bleeding. Secondary outcomes included pulmonary thrombotic load score (Miller), improvement in right ventricular-to-left ventricular ratio (RV/LV), dose and duration of the thrombolytic drug tissue plasminogen activator (tPA), length of stay (LOS) in the ICU, and total LOS in the hospital.ResultsA total of seven articles and 451 patients were included in this study. 241 patients were in the USAT group and 210 patients were in the SCDT group. There were no significant differences in all-cause mortality, total bleeding, and major bleeding between the two groups. Miller scores for pulmonary thrombus also showed no difference between the two groups, but pulmonary artery systolic pressure (PASP) was lower in the SCDT group after-treatment. The reduction of RV/LV from baseline was more pronounced in the SCDT group than in the USAT group (OR: −0.14, 95%CI: −0.20 to 0.07, P < 0.0001, I2 = 0%). Total dose of tPA and duration of infusion in the USAT group were lower than those in the SCDT group, but there was no significant statistical difference. LOS in the ICU was similar between the two groups, while LOS in the hospital was lower in the SCDT group.ConclusionThis study did not detect any differences in all-cause mortality, total bleeding, and major bleeding between non-low-risk aPE patients treated with USAT or SCDT. Improvement in right ventricular function was better in the SCDT group, and hospital LOS was lower in the SCDT group.

Off-label dose direct oral anticoagulants and clinical outcomes in Asian patients with atrial fibrillation: A new evidence of Asian dose

AimThis study aimed to evaluate the label compliance of DOACs in the Chinese AF population and explore the relationship between inappropriate DOACs dosage and clinical results. Methods and resultsThis is a retrospective multicenter cohort study conducted in 14 centers in China. According to the China Food and Drug Administration(CFDA) label and the recommendations of international guidelines, we divided patients into on-label dosage and off-label dosage. We then compared the clinical results after propensity score matching. We collect demographic information through the hospital information system and obtain clinical events through follow-up of patients or their families. Clinical results include major, minor, total bleeding, thrombosis, and all-cause death. 4191 patients with non-valvular AF (NVAF) were included, and approximately 55.6% and 1.7% of AF patients received off-label underdose and off-label overdose of DOACs, respectively. Compared with the on-label dose, DOACs with off-label underdose were associated with a significantly reduced risk of major bleeding (P = 0.004, OR = 0.23,95% CI: 0.08–0.69) and all-cause death (P<0.001, OR = 0.49,95% CI: 0.33–0.73). However, there was no significant difference in thrombotic events (P = 0.865 OR = 1.06,95% CI: 0.54–2.07) and minor bleeding (P = 0.465, OR = 1.10,95% CI: 0.85–1.43) risk. ConclusionsAbout 57.3% of Asian AF patients received an off-label dose of DOACs in daily practice. Off-label underdose DOACs were associated with significantly lower risks of major bleeding, all-cause death, and similar risks of minor bleeding, thrombotic events compared with on-label dose DOACs. Further prospective randomized trials are needed to determine the optimal dose of DOACs in Asian patients with AF at high bleeding risk.

Clinical outcomes of percutaneous coronary intervention and rotational atherectomy using second generation drug eluting stents: a Korean multicentre analysis

Abstract Background The aim of this study was to compare the clinical outcomes of different second generation drug-eluting stents (DES) in patients with calcified coronary lesions who underwent percutaneous coronary intervention using rotational atherectomy. Methods This study was based on a multicentre registry which enrolled patients with calcified coronary artery disease who received RA during between January 2010 and October 2019 from 9 tertiary centres in Korea. The primary outcome was target-vessel failure (TVF), defined as the compositae of cardiac death, target-vessel myocardial infarction (MI), and target-vessel revascularisation (TVR). The secondary outcomes were all-cause death, cardiac death, target vessel MI, TVR, cardiovascular accident, stent thrombosis, and total bleeding. Results 540 patients who underwent PCI after RA were enrolled and followed up for a median period of 16.1 months. From this registry, 439 patients who were treated using second generation DES were selected for further analysis. They were divided into four groups based on the characteristics of the stents used during the procedure. [Group I cobalt-chromium sirolimus eluting stent (CoCr-SES): Ultimaster 48 &amp; Orsiro 30, Group II platinum-chromium everolimus eluting stent (PtCr-EES): Synergy 93 &amp; Promus 70, Group III cobalt-chromium everolimus eluting stent (CoCr-EES): Xience 105, Group IV zotarolimus eluting stent (ZES): Resolute 93] There was no inter-group difference in procedural success rates, and the primary outcome of TVF showed no difference across the four groups (I: 10.3%, II: 13.5%, III: 13.3%, IV: 15.1%, log-rank p=0.922). Even after multivariate Cox regression analysis, there was no significant difference in TVF, or the secondary outcomes of all-cause death, cardiac death, target vessel MI, TVR, cardiovascular accident, stent thrombosis, and total bleeding. Conclusions There was no difference in procedural success rates and clinical outcomes between four different types of second-generation DES (CoCr-SES, PtCr-EES, CoCr-EES, ZES) in patients who underwent PCI using RA. Funding Acknowledgement Type of funding sources: None.

Reduction of major adverse and major cardiovascular events in patients with atrial fibrillation and stent implantation treated with left atrial occlusion device vs oral anticoagulants strategy

Abstract Background Treatment of patients with Nonvalvular Atrial Fibrillation (NVAF) who need coronary stent implantation is a challenge. Although trials have shown “direct anticoagulants (DOAC) indefinitely plus clopidogrel for one year” strategy reduces bleeding events in comparison to triple therapy, especially with warfarin, many questions remain about the safety and efficacy of this strategy. Purpose This study compared the events in patients who received left atrial appendage occlusion (LAAO) and antiplatelet therapy (APT) with those who were treated with oral anticoagulants (OAC) (including DOAC) and APT. Methods 207 consecutive patients with NVAF who underwent coronary stent implantation (most of them for NSTEACS), were analysed. 146 were treated with OAC (75 with acenocoumarol, 71 with DOAC) and 61 with LAAO during a mean follow-up of 35 months. Furthermore, they received APT according to the clinical cardiologist criteria (Figure 1). Results There were no significant differences in variables like age (average 75.7 years-old) hypertension, diabetes, gender, permanent or paroximal AF or a history of stroke or thromboembolisms between groups. But there were more unfavourable characteristics in LAAO group with significant differences in the percentage of history of coronary artery disease (43.2% vs 75,4% p= &amp;lt;0.001), CHA2DS2-VASc (4.07±1.70 vs 4.56±1.53 p=0.033), history of relevant bleedings (BARC ≥2) (8.9% vs 49.2% p&amp;lt;0.001), history of high bleeding risks defined as previous bleedings or HASBLED ≥3 (19.9% vs 62.3% p&amp;lt;0.001) and HAS-BLED (1.63±1.09 vs 2.49±1.18, p&amp;lt;0.001), between OAC and LAAO groups respectively. Observed total death, stroke/TIA and relevant bleedings incidence rates (expressed per 100 patient-years) were higher in OAC- than in LAAO-group: 10.86 vs. 6.96% (HR: 1.56; p=0.183), 4.59 vs. 1.27% (HR: 3.61; p=0.084), 12.43 vs. 4.57% (HR: 2.72; p=0.014), respectively. The composite events of MAE and MCVE (defined as in Figure 1 and 2) were also significantly higher: 23.40 vs. 9.8% (HR: 2.40; p=0.002) (Figure 2, left) and 7.41 vs. 1.9% (HR: 3.90; p=0.025) (Figure 2, right), respectively. Conclusions In patients with NVAF receiving coronary stents, a LAAO strategy with APT, shows better results in MAE and MCVE than treatment with OAC (DOAC included) plus APT strategy in a long term-follow-up, despite more unfavourable variables in LAAO group. Funding Acknowledgement Type of funding sources: None.

Outcome of anticoagulation with rivaroxaban in patients with non-retrieved inferior vena cava filters for the prevention of filter thrombosis: a retrospective cohort study

BackgroundNon-retrieved inferior vena cava filter (IVCF) is associated with some severe complications, such as filter thrombosis. The aim of this retrospective cohort study was to evaluate the outcome of rivaroxaban for the prevention of filter thrombosis in patients with non-retrieved IVCF.MethodsThe study based on the VTE registry databases was limited to patients with non-retrieved IVCF treated at Nanjing Drum Tower Hospital from January 2012 to December 2017. Outcomes included filter thrombosis, total bleeding events, death.ResultsA total of 202 patients were enrolled in the study and divided into rivaroxaban group and warfarin group. Mean follow-up period of the two groups was 57.4 ± 20.8 and 62.2 ± 23.0 months, respectively. In risk factors for VTE, transient factors (P = 0.008) and history of VTE (P = 0.028) were statistically different between the two groups. A total of 13 (6.4%) patients developed filter complications, of which 4 (3.5%) and 5 (5.7%) patients in rivaroxaban group and warfarin group developed filter thrombosis, respectively, without significant difference (P = 0.690). The total bleeding events in rivaroxaban group, including major bleeding and clinically relevant and non-major (CRNM) bleeding, were significantly lower than that in warfarin group (P = 0.005). Adjusting for hypertension, transient risk factors, history of VTE and cancer, no differences in the hazard ratio for outcomes were notable.ConclusionsIt is necessary to perform a concomitant anticoagulation in patients with non-retrieved filters. Rivaroxaban can be an alternative anticoagulant option for the prevention of filter thrombosis.

Dual therapy with oral anticoagulation and single antiplatelet agent versus monotherapy with oral anticoagulation alone in patients with atrial fibrillation and stable ischemic heart disease: a systematic review and meta-analysis.

In patients with atrial fibrillation (AF) and stable ischemic heart disease, recent guidelines recommend oral anticoagulant (OAC) monotherapy in preference to OAC + single antiplatelet agent (SAPT) dual therapy. However, these data are based on the results of only two randomized controlled trials (RCTs) and a relatively small group of patients. Thus, the safety and efficacy of this approach may be underpowered to detect a significant difference. We hypothesized that OAC monotherapy will have a reduced risk of bleeding, but similar all-cause mortality and ischemic outcomes as compared to dual therapy (OAC + SAPT). A systematic search of PubMed/MEDLINE, EMBASE, and Scopus was conducted. Safety outcomes included total bleeding, major bleeding, and others. Efficacy outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and major adverse cardiovascular events (MACE). RCTs and observational studies were pooled separately (study design stratified meta-analysis). Subgroup analyses were performed for vitamin K antagonists and direct oral anticoagulants (DOACs). Pooled risk ratios (RR) with corresponding 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method. Meta-analysis of 2 RCTs comprising a total of 2905 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant increase in major bleeding (RR 1.51; 95% CI [1.10, 2.06]). There was no significant reduction in MACE (RR 1.10; [0.71, 1.72]), stroke (RR 1.29; [0.85, 1.95]), myocardial infarction (RR 0.57; [0.28, 1.16]), cardiovascular mortality (RR 1.22; [0.63, 2.35]), or all-cause mortality (RR 1.18 [0.52, 2.68]). Meta-analysis of 20 observational studies comprising 47,451 patients showed that dual therapy (OAC + SAPT) vs. OAC monotherapy was associated with a statistically significant higher total bleeding (RR 1.50; [1.20, 1.88]), major bleeding (RR = 1.49; [1.38, 1.61]), gastrointestinal bleeding (RR = 1.62; [1.15, 2.28]), and myocardial infarction (RR = 1.15; [1.05, 1.26]), without significantly lower MACE (RR 1.10; [0.97, 1.24]), stroke (RR 0.93; [0.73, 1.19]), cardiovascular mortality (RR 1.11; [0.95, 1.29]), or all-cause mortality (RR 0.93; [0.78, 1.11]). Subgroup analysis showed similar results for both vitamin K antagonists and DOACs, except a statistically significant higher intracranial bleeding with vitamin K antagonist + SAPT vs. vitamin K antagonist monotherapy (RR 1.89; [1.36-2.63]). In patients with AF and stable ischemic heart disease, OAC + SAPT as compared to OAC monotherapy is associated with a significant increase in bleeding events without a significant reduction in thrombotic events, cardiovascular mortality, and all-cause mortality.

P9.45: Report of the First Cases of Hepatic SPLIT for Liver Transplantation in Peru

Introduction: Liver SPLIT is the surgical technique used in liver transplantation in which a liver graft from a cadaveric donor can be used for two recipients on the waiting list, these recipients being both adults and one adult and one pediatric. In Peru, a country with a poor donation rate, the implementation of this technique was very beneficial since through it we expand the donation pool and we can help our patients on the waiting list for liver transplantation. Materials and methods: In the first transplant operation with the SPLIT technique, it was from a 33-year-old donor Cause of death Ischemic stroke, ideal, who underwent complete right and complete left hepatic partitioning for a 48-year-old adult male diagnosed with autoimmune hepatitis and a 13-year-old female patient diagnosed with cystic fibrosis and hepatopulmonary syndrome. In the second transplant operation with the SPLIT technique, it was from a 37-year-old donor, cause of death due to severe ECT, ideal, who underwent complete right and complete left hepatic partitioning for a 52-year-old adult female patient with cirrhosis due to virus C and a 10-year-old male patient diagnosed with allagille syndrome. Results: □first operative: □Adult male right liver recipient □TIF: 417 min; ICT: 45 min. TOTAL: 462 min. Total bleeding 5000 cc □Girl left liver receptor □TIF: 660 min; ICT: 55 min. TOTAL: 715 min. Total bleeding 11000 cc □second operative: □Adult female right liver recipient □TIF:621min; ICT: 49 min. TOTAL: 710 min. Total bleeding 3800 cc □Recipient boy left liver □TIF: 744 min; ICT: 65 min. TOTAL: 809 min. Total bleeding 3000 cc Conclusion: Liver transplantation with the SPLIT technique is an option to expand the pool of donors and is a reality in our country, hoping to make further progress in order to continue helping our patients on the waiting list. The described procedure is effective and must be performed by experienced surgical teams and under high standards of quality and excellence.

Impact of Bleeding on Myocardial Infarction, Stroke, and Death During 12 Months Dual Antiplatelet Therapy After Acute Coronary Syndrome

BackgroundBleeding remains a complication during dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). Some data suggest a link between bleeding and worsened vascular outcomes. However, this association is unclear, due to omitting of minor bleedings when applying conservative scales. In contrast, the Platelet Inhibition and Outcomes (PLATO) trial classification used broad realistic capturing of all bleedings. MethodsAccess was gained to the Food and Drug Administration-issued adjudication data set on which post hoc analyses of bleeding, myocardial infarction (MI), stroke, and death were conducted. Bleeding was defined as minimal, minor, major, and life-threatening or fatal (LTOF) as per the original PLATO scale. ResultsAmong 18,624 enrollees, 10,705 adjudicated events occurred across 7171 patients. There were 618 minimal, 1412 minor, 1216 major, and 536 LTOF bleedings for the total of 3782 events reported in 3387 patients. There were 938 deaths, 2751 MIs and 359 strokes. The overall bleeding was 20.3%, exhibited in 19.2% patients. Total bleeds were associated with less deaths (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.47-0.63) and MI (OR: 0.47, 95% CI: 0.41-0.54; P < .001 for both). There were no differences in deaths (OR: 1.11, 95% CI: 0.93-1.34; P = .24), but less MIs (OR: 0.72. 95% CI: 0.59-0.86; P < .001), and more strokes (OR: 2.17, 95% CI: 1.64-2.88; P < .001) after LTOF. Major, minor, and minimal bleeds were associated with less deaths and MI but not strokes. ConclusionThese large uniformly adjudicated data reveal that within 12 months of dual antiplatelet therapy, 1 out of 5 patients experiences bleeding. Overall, bleeding was associated with diminished incidence of death and MI but not strokes.

Ticagrelor versus Clopidogrel in Patients with Severe Renal Insufficiency Undergoing PCI for Acute Coronary Syndrome.

Background Current guidelines recommend the use of potent antiplatelet agents in patients undergoing percutaneous coronary intervention (PCI) following an acute coronary syndrome (ACS). However, data about optimal platelet inhibition in severe renal insufficiency patients are scarce. The purpose of this study is to determine if ticagrelor is more effective than clopidogrel in patients with ACS and severe renal insufficiency treated with PCI. Methods We retrospectively enrolled patients with ACS and severe renal insufficiency (eGFR ≤ 30 ml/min·1.73 m2 or dialysis) who underwent PCI at our hospital between January 2015 and March 2020. We used the adjusted Cox proportional hazards models to analyze the 1-year outcome endpoints, including the primary endpoint (the composite of cardiovascular death, recurrence of MI, or nonfatal ischemic stroke), death from any cause, and bleeding events (Bleeding Academic Research Consortium, BARC criteria). Results A total of 276 patients with ACS and severe renal insufficiency who were treated with PCI with ticagrelor (n = 108) or clopidogrel (n = 168) were included in the study. After adjustment, there was no statistical difference in risk of the primary endpoint (HR, 0.78; 95% CI, 0.46–1.33; P=0.367) and death from any cause (HR, 0.86; 95% CI, 0.38–1.89; P=0.708) in the ticagrelor group against the clopidogrel group. However, the risk of total bleeding was significantly higher in the ticagrelor group (HR, 3.01; 95% CI, 1.81–5.62; P=0.01). Subgroup analysis according to the confounders did not identify any significant subgroup heterogeneity. Conclusion Ticagrelor did not improve the major adverse cardiovascular events and all-cause mortality when compared to clopidogrel, but significantly increased the risk of bleeding in Chinese patients with ACS and severe renal insufficiency undergoing PCI.

Meta-Analysis of the Efficacy and Safety of Tranexamic Acid in Spinal Surgery.

Objective The safety and effectiveness of topical tranexamic acid in spinal surgery has not yet been reached, and further research is needed to confirm it. This study is aimed at detecting the effectiveness and safety on the tranexamic acid in spinal surgery. Methods The Cochrane Library, PubMed, Embase, CNKI, and other databases were searched. The search time was from 2016 to 2019. All randomized controlled trials comparing the topical tranexamic acid group and the control group were collected. The experimental group used topical application. Tranexamic acid was used to treat bleeding after spinal surgery. The control group was no tranexamic acid or isotonic saline. The total bleeding, blood transfusion rate, and the occurrence of deep vein thrombosis were compared between the two groups. Rev Man 5.2.0 software was used for meta-analysis. Results A total of 8 randomized controlled trials were included, including 884 patients. Meta-analysis results showed that the total bleeding volume of the tranexamic acid group was lower than that of the control group, and the difference was statistically significant weighted mean difference ((WMD) = –360.27 mL, 95% confidence interval (CI) (–412.68, –307.87) mL, P < 0.00001). The blood transfusion rate in the tranexamic acid group was lower than that in the control group (odds ratio (OR) = 0.22, 95% CI (0.14, 0.33), P < 0.00001). There was no significant difference in the incidence of deep vein thrombosis between the two groups: OR = 1.48, 95% CI (0.41, 5.34), P = 0.55. Conclusion Tranexamic acid can significantly reduce perioperative total blood loss, intraoperative blood loss, and blood transfusion rate during spinal surgery but has no significant effect on blood transfusion and thrombosis.