Incidence Of Major Bleeding Research Articles

External validation of the PE-SARD risk score for predicting early bleeding in acute pulmonary embolism in the RIETE Registry

IntroductionThe PE-SARD score (syncope, anemia, renal dysfunction) was developed to predict the risk of major bleeding in the acute phase of pulmonary embolism (PE). MethodsWe analyzed data from 50,686 patients with acute PE included in the RIETE registry to externally validate the PE-SARD score. We calculated the overall reliability of the PE-SARD score, as well as discrimination and calibration for predicting the risk of major bleeding at 30 days. The performance of PE-SARD was compared to the BACS and PE-CH models. ResultsDuring the first 30 days, 640 patients (1.3 %) had a major bleeding event. The incidence of major bleeding within 30 days was 0.6 % in the PE-SARD-defined low-risk group, 1.5 % in the intermediate-risk group, and 2.5 % in the high-risk group, for an OR of 2.22 (95 % CI, 2.02–2.43) for the intermediate-risk group (vs low-risk group), and 3.94 for the high-risk group (vs low-risk group). The corresponding sensitivity was 81.1 % (intermediate/high vs low risk), and specificity was 85.9 % (95 % CI, 85.8–86.1) (low/intermediate vs high risk). The applicability of PE-SARD was consistent across clinically relevant patient subgroups and over shorter time periods of follow-up (i.e., 3 and 7 days). The C-index was 0.654 and calibration was excellent. The PE-SARD bleeding score improved the major bleeding risk prediction compared with the BACS and PE-CH scores. ConclusionsThe PE-SARD score identifies PE patients with a higher risk of bleeding, which could assist providers for potentially adjusting PE management, in a framework of shared decision-making with individual patients.

Argatroban as an Add-On to rtPA in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Current treatment options for acute ischemic stroke, including intravenous thrombolysis (IVT) and mechanical thrombectomy, have undoubtedly revolutionized stroke care. The need for additional treatment options has brought into the light direct thrombin inhibitors (DTIs) and, specifically, argatroban as a promising candidate. However, there is uncertainty regarding the safety of adding argatroban to IVT, mainly due to the increased hemorrhagic risk. In this study, we performed a systematic review and meta-analysis examining the safety and efficacy of argatroban as an add-on treatment for IVT. The following databases were searched from inception until the 14th of May 2023: Pubmed/MEDLINE, ClinicalTrials.gov, the EU Clinical Trials Register, EMBASE/Scopus, and the Cochrane Library. Only randomized clinical trials (RCTs) enrolling patients with acute ischemic stroke who underwent IVT evaluating the add-on use of any DTIs were selected for the systematic review and further meta-analysis. The PRISMA guidelines were followed at all stages. Four studies with argatroban were included in the final analysis. Analysis of risk ratio and relative risk shows that the add-on therapy with argatroban seems to be effective and favors a good clinical outcome (mRS 0-2) at 90 days, similar to that of alteplase. All studies showed a low pooled incidence of symptomatic intracerebral hemorrhage (5%), parenchymal hematoma (3%), and other major bleeding (1%). Argatroban as an add-on treatment to IVT seems not to be associated with excessive bleeding risk; however, its efficacy remains unproven. According to this synopsis of the currently available evidence, it is premature to use argatroban as an add-on to IVT treatment outside the current clinical trial setting.

Venous thromboembolism in critically ill adult patients with hematologic malignancy: a population-based cohort study.

The aim of this study was to describe the incidence of venous thromboembolism (VTE) and major bleeding among hospitalized patients with hematologic malignancy, assessing its association with critical illness and other baseline characteristics. We conducted a population-based cohort study of hospitalized adults with a new diagnosis of hematologic malignancy in Ontario, Canada, between 2006 and 2017. The primary outcome was VTE (pulmonary embolism or deep venous thrombosis). Secondary outcomes were major bleeding and in-hospital mortality. We compared the incidence of VTE between intensive care unit (ICU) and non-ICU patients and described the association of other baseline characteristics and VTE. Among 76,803 eligible patients (mean age 67years [standard deviation, SD, 15]), 20,524 had at least one ICU admission. The incidence of VTE was 3.7% in ICU patients compared to 1.2% in non-ICU patients (odds ratio [OR] 3.08; 95% confidence interval [CI] 2.77-3.42). The incidence of major bleeding was 7.6% and 2.4% (OR 3.33; 95% CI 3.09-3.58), respectively. The association of critical illness and VTE remained significant after adjusting for potential confounders (OR 2.92; 95% CI 2.62-3.25). We observed a higher incidence of VTE among specific subtypes of hematologic malignancy and patients with prior VTE (OR 6.64; 95% CI 5.42-8.14). Admission more than 1year after diagnosis of hematologic malignancy (OR 0.64; 95% CI 0.56-0.74) and platelet count ≤ 50 × 109/L at the time of hospitalization (OR 0.63; 95% CI 0.48-0.84) were associated with a lower incidence of VTE. Among patients with hematologic malignancy, critical illness and certain baseline characteristics were associated with a higher incidence of VTE.

Cancer-associated venous thromboembolism in the direct oral anticoagulants era: Insight from the COMMAND VTE Registry-2

BackgroundThere is a paucity of data on real-world management strategies and clinical outcomes of cancer-associated venous thromboembolism (VTE) in the direct oral anticoagulants (DOACs) era. ObjectivesTo investigate the status of cancer-associated VTE in the DOAC era. MethodsThis multicenter, retrospective cohort study among 31 centers in Japan between 2015 and 2020 enrolled 5197 consecutive patients with acute symptomatic VTE, who were divided into 1507 patients (29 %) with active cancer and 3690 patients (71 %) without. ResultsThe cumulative 3-year rate of anticoagulation discontinuation was significantly higher in patients with active cancer than in those without (62.7 % vs. 59.1 %, P < 0.001). The cumulative 5-year incidence of recurrent VTE was higher in patients with active cancer than in those without (10.1 % vs. 9.1 %, P = 0.01), however, after adjusting for the confounders and competing risk of mortality, the excess risk of the active cancer group relative to the no active cancer group was no longer significant (HR: 0.95, 95 % CI: 0.73-1.24). The cumulative 5-year incidence of major bleeding was much higher in the active cancer group (20.4 % vs. 11.6 %, P < 0.001). Even after adjusting for the confounders and competing risk of mortality, the risk of the active cancer group relative to the no active cancer group remained significant (HR: 1.36, 95 % CI: 1.11–1.66). ConclusionsThe current large real-world registry revealed that the risk of major bleeding was still higher in patients with active cancer than in those without, leading to the frequent anticoagulation discontinuation, which has been still a huge challenge to overcome in the DOAC era.

Prognosis in Patients with ST-Segment Elevation Myocardial Infarction Reperfused by PHDP: 1-Year MACEs Follow-Up.

This study explored 1-year follow-up of Parmaco-invasive strategy with half-dose recombinant human prourokinase (PHDP) in patients with acute ST-segment elevation myocardial infarction (STEMI). The follow-up endpoints were major adverse cardiovascular events (MACEs) occurring within 30 days and 1 year, as well as postoperative bleeding events. The study ultimately included 150 subjects, with 75 in the primary percutaneous coronary intervention (PPCI) group and 75 in the PHDP group. This study found that the PHDP group had a shorter FMC-reperfusion time (42.00 min vs 96.00 min, P < 0.001). During PCI, the PHDP group had a lower percutaneous transluminal coronary angioplasty (PTCA) (P = 0.021), intropin (P = 0.002) and tirofiban (P < 0.001) use. And the incidence of intraoperative arrhythmia, malignant arrhythmia, and slow flow/no-reflow was lower in the PHDP group (P < 0.001). At the 30-day follow-up, there was a significantly higher proportion of patients in the PPCI group who were readmitted due to unstable angina (P = 0.037). After 1 year of follow-up, there was no statistically significant difference in MACEs between the two groups (P = 0.500). The incidence of postoperative major bleeding, intracranial bleeding, and minor bleeding did not differ between the PHDP and PPCI groups (P > 0.05). The PHDP facilitates early treatment of infarct-related vessels, shortens FMC-reperfusion time, and does not increase the risk of MACEs.

Efficacy and safety of direct oral anticoagulants for preventing venous thromboembolism in hospitalized cancer patients: a national multicenter retrospective cohort study.

Studies on the use of direct oral anticoagulants (DOACs) for preventing venous thromboembolism (VTE) in hospitalized cancer patients are lacking. Therefore, we conducted a multicenter retrospective cohort study to evaluate the efficacy and safety of DOACs versus low-molecular-weight heparin (LMWH) for the primary prevention of VTE in hospitalized cancer patients. Clinical outcomes included thrombosis, VTE, other thrombosis, all bleeding, major bleeding, nonmajor bleeding, and all-cause death. A 1:1 cohort of rivaroxaban and LMWH patients was created by propensity score matching. A total of 2,385 cancer patients were included in this study. During the 3-month follow-up period, 129 (5.4%) thrombosis events occurred, 63 (2.7%) of which were VTEs and 66 (2.8%) of which were other thrombosis events. All bleeding occurred in 163 (6.8%) patients, 68 (2.9%) had major bleeding, and 95 (4.0%) had nonmajor bleeding. All-cause deaths occurred in 113 (4.7%) patients. After adjusting for various confounders, the incidence of thrombosis and other thromboses was significantly lower in the rivaroxaban group than in the LMWH group [OR 0.543, 95% CI (0.343-0.859), p = 0.009; OR 0.461, 95% CI (0.241-0.883), p = 0.020]. There were no significant differences in incidence of VTE, total bleeding, major bleeding, nonmajor bleeding, or all-cause death. In oncology patients receiving thromboprophylaxis, rivaroxaban has a lower incidence of thrombosis and other thrombosis and a similar incidence of VTE as LMWH and does not increase the risk of bleeding. Rivaroxaban may be an attractive alternative to LMWH for preventing VTE in hospitalized cancer patients.

Robotic-assisted Navigation Bronchoscopy: A Meta-Analysis of Diagnostic Yield and Complications.

Robotic-assisted navigation bronchoscopy (RANB) is a novel method to biopsy lung nodules, with initial reports demonstrating excellent accuracy. We aimed to evaluate pooled estimates of diagnostic yields and complication rates with RANB by performing a meta-analysis of the available literature. We searched 3 databases, including PubMed, EmBase, and Web of Science. The resulting abstracts were reviewed by 2 investigators. Analyses were performed using random effects models, and diagnostic yield and complication rates were estimated after the Freeman-Tukey transformation. A total of 23 articles, comprising 1409 patients and 1541 nodules, were included in the final analysis. Mean ages ranged from 63.2 to 69.3 years. The average size of the nodules ranged between 5.9 and 25.0mm. Most patients (54.0% to 92.0%) had a current or prior smoking history in studies that reported them (n=8). The pooled diagnostic yield was 81.9% (12 studies, 838 nodules, 95% CI: 83.4%-91.0%), and the pooled sensitivity for malignancy was 87.6% (8 studies, 699 nodules, 95% CI: 81.3%-89.5%). The pooled incidence of pneumothorax rates was 0.60% (95% CI: 0.11%-1.35%). The pooled incidence of major bleeding was <0.01%. Diagnostic yield for patients with pulmonary nodules undergoing RANB is high, though may be impacted by the prevalence of malignancy, participant selection, and publication bias. Complication rates, including pneumothoraces and bleeding rates, appear low across all studies. If RANB is available, clinicians should consider utilizing this platform to biopsy pulmonary nodules.

A Novel Risk Score for Major Bleeding in Japanese Patients with Non-Valvular Atrial Fibrillation: The J-RISK AF Study.

Oral anticoagulants (OACs) reduce the risk of ischemic stroke but may increase the risk of major bleeding in patients with non-valvular atrial fibrillation (NVAF). Various risk scores, such as HAS-BLED, ATRIA, ORBIT, and DOAC, have been proposed to assess the risk of major bleeding in patients with NVAF receiving OACs. However, limited data are available regarding bleeding risk stratification in Japanese patients with NVAF. Of the 16,098 NVAF patients from the J-RISK AF study, the combined data of the five major AF registries in Japan (J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry), we analyzed 11,539 patients receiving OACs (median age, 71 years old; women, 29.6%; median CHA2DS2-VASc score, 3). During the 2-year follow-up period, major bleeding occurred in 274 patients (1.3% per patient-year). In a multivariate Cox proportional hazards analysis, an advanced age, hypertension (systolic blood pressure ≥ 150 mmHg), bleeding history, anemia, thrombocytopenia, and concomitant antiplatelet agents were significantly associated with a higher incidence of major bleeding. We developed a novel risk stratification system, HED-[EPA]2-B3 score, which had a better predictive performance for major bleeding (C-statistics 0.67, [95% confidence interval, 0.63-0.70]) than the HAS-BLED (0.64, [0.60-0.67], P for difference 0.02) and ATRIA (0.63, [0.60-0.66], P for difference ＜0.01) scores. Furthermore, it was non-significantly higher than the ORBIT (0.65, [0.62-0.68], P for difference 0.07) and DOAC (0.65, [0.62-0.68], P for difference 0.17) scores. Our novel risk stratification system, the HED-[EPA]2-B3 score, may be useful for identifying Japanese patients receiving OACs at a risk of major bleeding.

Real-World Clinical Outcomes of Warfarin Use Among Patients with Chronic Kidney Disease in Thailand

Background: Warfarin has been extensively used for a long time under various conditions. However, comprehensive evidence is scarce regarding the effectiveness and safety of warfarin in each group of chronic kidney disease (CKD) among Thai patients. Objective: The present study used real-world data from Thailand to determine the incidence of thromboembolism and bleeding among patients with CKD with different estimated glomerular filtration rates (eGFRs). Materials and Methods: A retrospective cohort study was conducted among Thai patients with CKD who used warfarin at three tertiary-care hospitals between January 2015 and December 2019. Patients were included and divided into five groups according to their eGFRs as N1 to N5 with eGFR greater than 60, 30 to 59, 15 to 29, less than 15 and not receiving dialysis, and less than 15 mL/minute/1.73 m² with dialysis, respectively. The incidence density was analyzed to report thromboembolism and bleeding outcomes. Results: During the follow-up period, 2.28 per 100 person-years of patients developed thromboembolism with N1 to N5 at 2.00, 2.27, 3.68, 4.66, and 1.70 per 100 person-years, respectively. Furthermore, 2.33 per 100 person-years of patients developed major bleeding with N1 to N5 at 1.17, 2.25, 4.03, 11.37, and 5.12 per 100 person-years, respectively. Conclusion: The present study found that the incidence of thromboembolism and major bleeding among patients with CKD increased across different eGFR groups who used warfarin. Interestingly, patients with CKD in the N4 group had a higher incidence of thromboembolism and major bleeding than the other groups. Thus, close monitoring and frequent follow-up are recommended for this group. Keywords: Vitamin K antagonist; Bleeding; Thromboembolism; Chronic kidney disease

Very early invasive strategy in higher risk non-ST-elevation acute coronary syndrome: the RAPID NSTEMI trial

ObjectiveTo investigate whether a very early invasive strategy (IS)±revascularisation improves clinical outcomes compared with standard care IS in higher risk patients with non-ST-elevation acute coronary syndrome (NSTE-ACS).MethodsMulticentre, randomised, controlled, pragmatic...

Major in-hospital complications after catheter ablation of cardiac arrhythmias: individual case analysis of 43 031 procedures.

In-hospital complications of catheter ablation for atrial fibrillation (AF), atrial flutter (AFL), and ventricular tachycardia (VT) may be overestimated by analyses of administrative data. We determined the incidences of in-hospital mortality, major bleeding, and stroke around AF, AFL, and VT ablations in four German tertiary centres between 2005 and 2020. All cases were coded by the G-DRG- and OPS-systems. Uniform code search terms were applied defining both the types of ablations for AF, AFL, and VT and the occurrence of major adverse events including femoral vascular complications, iatrogenic tamponade, stroke, and in-hospital death. Importantly, all complications were individually reviewed based on patient-level source records. Overall, 43 031 ablations were analysed (30 361 AF; 9364 AFL; 3306 VT). The number of ablations/year more than doubled from 2005 (n = 1569) to 2020 (n = 3317) with 3 times and 2.5 times more AF and VT ablations in 2020 (n = 2404 and n = 301, respectively) as compared to 2005 (n = 817 and n = 120, respectively), but a rather stable number of AFL ablations (n = 554 vs. n = 612). Major peri-procedural complications occurred in 594 (1.4%) patients. Complication rates were 1.1% (n = 325) for AF, 1.0% (n = 95) for AFL, and 5.3% (n = 175) for VT. With an increase in complex AF/VT procedures, the overall complication rate significantly increased (0.76% in 2005 vs. 1.81% in 2020; P = 0.004); but remained low over time. Following patient-adjudication, all in-hospital cardiac tamponades (0.7%) and strokes (0.2%) were related to ablation. Major femoral vascular complications requiring surgical intervention occurred in 0.4% of all patients. The in-hospital mortality rate adjudicated to be ablation-related was lower than the coded mortality rate: AF: 0.03% vs. 0.04%; AFL: 0.04% vs. 0.14%; VT: 0.42% vs. 1.48%. Major adverse events are low and comparable after catheter ablation for AFL and AF (∼1.0%), whereas they are five times higher for VT ablations. In the presence of an increase in complex ablation procedures, a moderate but significant increase in overall complications from 2005-20 was observed. Individual case analysis demonstrated a lower than coded ablation-related in-hospital mortality. This highlights the importance of individual case adjudication when analysing administrative data.

Effectiveness of Early Direct Oral Anticoagulant Monotherapy within One Year of Coronary Stent Implantation in Patients with Atrial Fibrillation: A Nationwide Population-Based Study

We evaluated the effectiveness of early direct oral anticoagulant (DOAC) monotherapy within one year after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) using Korean National Health Insurance Service data. AF patients who underwent PCI were included and divided into the DOAC monotherapy group and the combination therapy group (DOAC with an antiplatelet agent) based on the medications used at 6 months after PCI. A major adverse cardiovascular event (MACE) was defined as a composite of cardiovascular death, acute myocardial infarction (AMI), stroke, or systemic thromboembolic event between 6 and 12 months after PCI. In the overall study population, the DOAC dose reduction rate was high in both the monotherapy group (70.8%) and the combination therapy group (79.1%). After propensity score matching, the MACE incidence was not significantly different between the two groups (hazard ratio [HR] 1.42 [0.90–2.24]). The numerical trend for higher MACE in the monotherapy group was mainly driven by the difference in stroke incidence (HR 1.84 [0.97–3.46]). All-cause death (HR 1.29 [0.61–2.74] or the incidence of major bleeding (HR 1.07 [0.49–2.35]) results were similar in the two groups. In conclusion, early DOAC monotherapy was not significantly associated with MACE risk between 6 and 12 months after PCI.

The Impact of Frailty on the Incidence of Major Bleeding in Octogenarian Patients Undergoing Percutaneous Coronary Intervention

The Impact of Frailty on the Incidence of Major Bleeding in Octogenarian Patients Undergoing Percutaneous Coronary Intervention

Risk scores for major bleeding from direct oral anticoagulants: comparing predictive performance in patients with atrial fibrillation

BackgroundDespite direct oral anticoagulants (DOACs) being safer than warfarin for stroke prevention in atrial fibrillation (AF), major bleeding concerns persist. Most bleeding risk scores predate DOAC approval. ObjectivesThis study aimed to compare the Age, history of Bleeding, and non-bleeding related Hospitalisation [ABH] score’s performance—derived for DOAC-treated patients—with those of 5 other scores (Anticoagulation and Risk Factors in Atrial Fibrillation [ATRIA], Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly [>65 years], Drugs/alcohol concomitantly [HAS-BLED], Hepatic, Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke [HEMORR2HAGES], Outcomes Registry for Better Informed Treatment of Atrial Fibrillation [ORBIT-AF], and Congestive heart failure, Hypertension, Age ≥75 [doubled], Diabetes, Stroke [doubled]-Vascular disease, Age 65–74, Sex category [CHA2DS2-VASc]) in predicting DOAC-related major bleeding in patients with AF. MethodsIn this retrospective study of 2364 patients with nonvalvular AF on rivaroxaban or apixaban (median age, 68.3 years; 32.1% women), International Society on Thrombosis and Haemostasis–defined major bleeding (incidence, 4.1%; n = 97) was analyzed. C-statistics from time-dependent receiver operating characteristic (ROC) curves for continuous risk scores were the primary comparison metric, but other metrics, such as decision curves, were also compared. ResultsAt 100 days, C-statistics were highest for ORBIT-AF and ATRIA (0.62 and 0.61, respectively, with other scores having an area under the ROC curve of <0.60); some significant differences favored ORBIT-AF. At 1100 days, C-statistics remained highest for ORBIT-AF and ATRIA (0.62 and 0.61, respectively, with other scores having an area under the ROC curve of <0.60 again), and ORBIT-AF had significantly higher C-statistics than those for all other risk scores (P < .05), except for ATRIA. At 2100 days, all C-statistics were <0.60 with no significant differences. Decision curves showed the greatest net benefit for ORBIT-AF and ATRIA at 100 days and for ATRIA at 1100 days, with no discernible net benefit for any of the scores at 2100 days. ConclusionORBIT-AF and ATRIA provided the best bleeding risk prediction within the first 1100 days. None of the 6 bleeding risk scores provided predictive benefit over 2100 days of DOAC treatment.

Avatrombopag for Adults with Early Versus Chronic Immune Thrombocytopenia

Background Avatrombopag (AVA) is a newer thrombopoietin receptor agonist (TPO-RA) with certain advantages over other TPO-RAs. AVA is currently approved to treat adults with immune thrombocytopenia (ITP) in the chronic disease phase (duration &amp;gt;12 months). However, no studies have evaluated the safety and effectiveness of AVA in newly diagnosed ITP (duration &amp;lt;3 months) or persistent ITP (duration 9-12 months), leaving open questions regarding its safety (including thromboembolic risk) and effectiveness in these patients, and also drastically limiting availability of the drug to patients with early ITP, for whom it is off label. We hypothesize that AVA has similar safety and effectiveness in all phases of ITP. Methods We performed a multicenter, observational cohort study of all adult patients with primary or secondary ITP at 4 hospitals treated with AVA to compare outcomes of patients with newly diagnosed or persistent ITP versus patients with chronic ITP. We collected patient and disease characteristics and characteristics and outcomes of AVA treatment, including dosing, platelet counts prior to and during treatment, adverse events, concurrent and rescue therapies for ITP, and platelet transfusions. Platelet outcomes included rates of response (R, the primary outcome, defined as platelet count of ≥50 × 10 9/L) and complete response (CR, platelet count ≥100 × 10 9/L), both on at least one measurement without requirement for rescue therapy. The response fraction (RF) and complete response fraction (CRF), fractions between 0 (representing no instance of response at any timepoint for a patient) and 1 (representing a response at all timepoints for a patient) were calculated for each patient from monthly measurements during the first six months of treatment with avatrombopag. Other outcomes included major bleeding, rescue therapy requirements, thrombocytosis, and adverse events. Results Patient Population. 75 patients were included, 23 patients with newly diagnosed or persistent ITP (17.7 patient-years of AVA exposure) and 52 patients with chronic ITP (65.3 patient-years of AVA exposure). The median (range) age was 55 (18-80) years in the newly diagnosed/persistent ITP group versus 66 (22-90) years in the chronic ITP group; approximately 65% of patients in each group were female. Platelet Outcomes. With regards to the primary outcome, R was achieved in a similar proportion of newly diagnosed/persistent ITP patients (91%) as in chronic ITP patients (96%), P=0.58. Similar proportions also achieved a CR: 86% newly diagnosed/persistent ITP patients versus 81% of chronic ITP patients, P=0.78. Mean RF and CRF were also similar between the two groups ( TABLE). The median platelet count at baseline and over the first six months of treatment by disease phase is illustrated in the FIGURE. Other Outcomes. Incidence of major bleeding and requirement for rescue therapy and platelet transfusion were low in the newly diagnosed/persistent group ( TABLE) and statistically similar to incidences in the chronic group. Safety. The incidence of thrombocytosis (platelet count ≥400 × 10 9/L on ≥1 measurement) was similar (44% in the newly diagnosed/persistent ITP group and 40% in the chronic ITP group). No patient developed an arterial thromboembolic event. No patient in the newly diagnosed/persistent group developed a venous thromboembolism (VTE) and only one patient in the chronic group developed a VTE. No patient in the newly diagnosed/persistent group discontinued AVA due to an adverse event or safety concern. The rate of thromboembolic complications in the entire cohort including 83.0 patient-years of AVA exposure was 1.2 thromboembolic events per 100 patient-years, considerably lower than prior phase 2 and 3 clinical trials of AVA in ITP (which together documented 11 thromboembolic events occurring over 72.4 patient-years of AVA exposure, or 15.2 thromboembolic events per 100 patient-years). Conclusions AVA was safe and effective in patients with newly diagnosed and persistent ITP, with outcomes numerically, statistically, and clinically similar to patients receiving AVA for chronic ITP. Given its lack of dietary restrictions and hepatotoxicity, access to AVA in early ITP could improve disease outcomes and patient health-related quality of life. Further studies are needed to confirm our findings and evaluate the ability of AVA to induce sustained responses off treatment in patients with early ITP.

Bleeding Risk from Anticoagulant Thromboprophylaxis in Patients with Multiple Myeloma

Introduction: Patients with multiple myeloma (MM) have a high risk of venous thromboembolism (VTE) due to unique disease-related (i.e., vascular inflammation, hyperviscosity) and treatment-related factors (i.e., immunomodulatory drugs [IMiDs], high-dose dexamethasone). Thromboprophylaxis is recommended for most patients starting MM therapy. Anticoagulants are preferred over aspirin except in patients at low risk for VTE. However, compliance with prophylaxis guidelines is low. The risk of bleeding from thromboprophylaxis is not well described in these patients so an excessive perceived risk may influence clinicians' practice. We conducted a real-world analysis of bleeding complications from VTE prophylaxis in MM. Methods: The IBM MarketScan Commercial Claims Database was used to identify MM cases between 2013 and 2021. Cases required MM diagnosis from 1 inpatient or 2 outpatient claims, based on ICD-9 or ICD-10 codes, and MM-specific therapy started between 7 days before and 90 days after index diagnosis code, based on HCPCS codes and prescription records. Those with preexisting VTE, atrial fibrillation or stroke were excluded. Thromboprophylaxis was defined as at least 1 prescription for warfarin, low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOAC) within 30 days of diagnosis. Major bleeding was defined as bleeding requiring hospitalization using inpatient ICD codes previously validated (Cunningham algorithm). Patients were followed from end of prophylaxis exposure window (index MM + 30 days) to first major bleeding event, disenrollment (due to death or other reasons) or December 31, 2021. Descriptive statistics were used to calculate rates of bleeding. Cox regression was used to assess the risk of bleeding from thromboprophylaxis and define risk factors associated with major bleeding. Results: We included 6,656 patients diagnosed and treated for MM, with mean age 62.7 years and 55.3% males. Although over 50% of the population would have had a high thrombotic risk based on consensus guidelines, concurrent anticoagulant prophylaxis was prescribed in only 6.6% (436). Prophylaxis agent of choice was warfarin in 23% (102), LMWH in 39% (169), and DOAC in 38% (165), respectively. There was a trend over time favoring DOAC over other agents (25% increase in DOAC use vs. other agents per year on average, p&amp;lt;0.01). Patients on prophylaxis had a higher rate of IMiD-based therapy (63.8% vs. 46.7%, p&amp;lt;0.01) and lower concomitant anti-platelet use (2.1% vs. 4.7%, p=0.01) than those not receiving prophylaxis. There were no differences in age/sex distribution, Charlson comorbidity index (CCI) or history of bleeding between groups. With a median 1.3 years follow-up, the incidence of major bleeding among MM patients receiving VTE prophylaxis was 1.4% or 7.8 bleeding events per 1,000 person-years. This was numerically but not statistically lower than the incident bleeding rate in patients not receiving prophylaxis: 1.8% or 10.1 events per 1,000 person-years. Table 1 shows risk factors for bleeding in this MM population, adjusting for age and sex, including higher age (per 10-year increase, HR 1.38), higher CCI (per SD increment, HR 1.18), history of bleeding (HR 1.54), hypertension (HR 1.87), and renal disease (HR 1.56). IMiD-based MM therapy was associated with decreased risk of bleeding (HR 0.69). Table 2 shows the estimated bleeding risk associated with prophylaxis across several models. No statistically significant association was identified between major bleeding and anticoagulant prophylaxis. Discussion: In a real-world analysis of commercial claims data, the risk of major bleeding associated with VTE prophylaxis in patients with MM undergoing cancer therapy is low and no significant increase in bleeding risk was identified for concurrent anticoagulant use. The rate of major bleeding events appears to be comparable between patients who receive VTE prophylaxis and those who do not. Nevertheless, underutilization of VTE prophylaxis is frequent. Higher CCI, bleeding history, hypertension, and renal disease were clinical factors associated bleeding risk, which may be included in models to help clinicians assess individual patient's risk and guide clinical decisions.

Nondual Antiplatelet Therapy Versus Dual Antiplatelet Therapy Before Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-analysis.

Transcatheter aortic valve replacement (TAVR) is an interventional procedure performed in patients with severe aortic stenosis and often required perioperative antiplatelet therapy. Most previous studies have focused on antiplatelet therapy following TAVR. However, few studies have investigated the prognostic effect of preoperative antiplatelet therapy in patients undergoing TAVR. This study aimed to compare the efficacy and safety of nondual antiplatelet therapy (non-DAPT) and DAPT before TAVR. We performed a systematic search of Embase, PubMed, and Web of Science until February 2023. Studies were eligible if they compared non-DAPT (single antiplatelet therapy or no antiplatelet therapy) with DAPT in patients before TAVR. A total of 5 studies, including 2329 patients, met the inclusion criteria and were included in the meta-analysis. Preoperative non-DAPT significantly decreased minor bleeding events compared with preoperative DAPT [odds ratio 0.58; 95% confidence interval: 0.44-0.76]. There were no significant differences in the incidence of other bleeding events, transfusions, stroke, myocardial infarction, or all-cause death. Preoperative single antiplatelet therapy significantly decreased the incidence of major bleeding compared with DAPT (odds ratio 0.14; 95% confidence interval: 0.04-0.48). Preoperative non-DAPT significantly reduced minor bleeding events in patients undergoing TAVR, without increasing the risk of stroke and myocardial infarction.

Long-term clinical outcomes of hemodialysis patients with acute coronary syndrome undergoing primary percutaneous coronary intervention

Abstract Background Number of hemodialysis (HD) patients, especially those with diabetic nephropathy (DN) has increased all over the world. It is well known that the leading cause of death in HD patients is cardiovascular event, however, little is known regarding the long-term clinical outcomes of hemodialysis (HD) patients with acute coronary syndrome (ACS) undergoing primary percutaneous coronary intervention (pPCI) in the current real-world setting. Purpose We aimed to characterize and clarify the long-term clinical outcome of HD patients with ACS undergoing pPCI. Method: Consecutive 531 patients (70.3±13.0 yrs, male 75.5%, 51 HD patients, 9.6% ) with ACS undergoing pPCI in our hospital from 2015 to 2019 were enrolled. The primary endpoint of the present study was the composite outcomes; all-cause death, any unplanned PCI after ACS, heart failure (HF) admission, major bleeding, non-fatal myocardial infarction (MI), non-fatal stroke, and stent thrombosis. Event rate in the studied subjects was stratified with the log-rank test. Result Incidence of the primary endpoint during the median follow-up period of 1515 days in HD patients was significantly higher than non-HD patients (94.1% in HD vs. 61.6% in non-HD; p&amp;lt;0.01, Figure 1). In HD patients, all-cause death, any unplanned PCI, HF hospitalization, and non-fatal MI were significantly more prevalent (52.9% in HD vs. 24.4% in non-HD; p&amp;lt;0.01, 52.9% in HD vs. 16.9% in non-HD; p&amp;lt;0.01, 19.6% in HD vs. 6.5% in non-HD; p&amp;lt;0.01, and 7.8% in HD and 2.1% in non-HD; p=0.04, respectively, Table 1). Incidence of major bleeding, non-fatal stroke and ST were comparable between the two groups (11.8% in HD vs. 7.3% in non-HD; p=0.27, 3.9% in HD vs. 2.7% in non-HD; P=0.64, and 0% in HD vs. 0.4% in non-HD, P=1.0, respectively). In the HD patients, incidence of primary endpoint in DN was similar compared with non-HD patients (93.9% in DN vs. 94.4% in non-DN; p=0.4). Incidence of primary endpoint in patients with HD duration longer than or equal to 6 years was also comparable to those in patients with HD duration less than 6 years (92.6% vs. 95.8%, p=0.09), however, 180-day primary endpoint in the former group was significantly higher than the latter group (66.7% vs 29.2%, P&amp;lt;0.01) due to all-cause death and major bleeding. Conclusion HD patients with ACS undergoing pPCI have extremely worse clinical outcomes with more all-cause death, any unplanned PCI, HF admission, and non-fatal MI even in the current pPCI era. In the long-term, diabetic nephropathy and longer HD years had no significant impact on the clinical outcomes, however those with longer HD years have an extremely poor prognosis in a short-term.

Impact of proton pump inhibitor on quality of anticoagulant control and outcomes in atrial fibrillation patients treated with an oral anticoagulant in the COOL-AF registry

Abstract Introduction Proton pump inhibitor (PPI) is commonly prescribed in patients treated with antithrombotic therapy, assuming it will reduce bleeding risk irrespective of the risk of bleeding. Although PPI may reduce the risk of gastrointestinal bleeding in those treated with an oral anticoagulant, PPI may increase INR by accelerating warfarin absorption, thereby increasing the risk of bleeding. We aimed to assess the impact of PPI use on outcomes and quality of anticoagulant control in AF patients treated with OAC. Methods The COOL-AF registry was a nationwide prospective observational study enrolling AF patients from 27 hospitals in Thailand between 2014 and 2017. The registry aimed to evaluate antithrombotic patterns, quality of OAC control, and clinical outcomes. Clinical information of patients was collected every six months and until three years. Patients treated with oral anticoagulants (either warfarin or non-vitamin K antagonist OAC (NOAC)) were included in the present analysis. Patients receiving any PPI type and dosage at the registry entry were counted as PPI users. Poor anticoagulant control was defined as time to therapeutic range (TTR) less than 65%. The association between PPI use and outcomes, including GI bleeding, overall bleeding, all-cause mortality, and ischemic stroke or systemic embolization, were assessed in the Cox model adjusted for age, prior GI bleeding, chronic alcohol use, chronic kidney disease, liver disease, smoking, and baseline anemia. Subgroup analyses were performed in patients at high bleeding risk (HAS-BLED score ≥ 3), and in patients concomitantly treated with antiplatelet. Results Of 3,402 patients in the registry, 2568 (75.5%) were treated with OAC at baseline. The prevalence of females was 43.4%, with a mean age of 68.4 years. The majority of patients (91.1%) received warfarin. The incidence of major bleeding was 2.11 (1.79–2.48) per 100 person-years. PPI was used at baseline in 707 patients (20.8%). Compared with their counterpart, PPI was more frequently used in high-bleeding risk patients (27.3% vs. 18.1%, p &amp;lt; 0.001) and in those with concomitant antiplatelet therapy (37.5% vs. 17.1%, p &amp;lt; 0.001). The mean TTR was similar between PPI and non-PPI users (52.5% vs. 53.8%, p 0.37). PPI use was not associated with poor anticoagulant control (adjusted OR 1.12, 95% 0.89-1.40). The risk of GI bleeding in PPI users was similar to non-user (adjusted HR 1.01, 95%CI 0.59-1.75). The risk of all-cause mortality, ischemic stroke or systemic embolization, and overall bleeding was not different between PPI and non-PPI users. There was no significant interaction between PPI use and bleeding risk or concomitant antiplatelet therapy on adverse outcomes. Conclusion PPI use has no impact on major outcomes, including bleeding in AF patients treated with OAC. The practice of concomitant prescribing of PPI in patients treated with OAC is needed to be re-examined, given the potentially high impact of health care costs.PPI use and outcomes

The efficacy and safety of direct oral anticoagulants compared with vitamin K antagonist in patients with hypertrophic cardiomyopathy and atrial fibrillation: a systematic review and meta-analysis

Abstract Background The benefit-risk profile of direct oral anticoagulants (DOAC) therapy in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) have not been well established yet. Purpose This study aimed to evaluate the efficacy and safety of DOAC compared with vitamin K antagonists (VKA) in patients with HCM and AF. Methods PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov were searched to identify studies comparing DOAC with VKA in patients with HCM and AF. Results Five studies involving 8103 patients were included in this meta-analysis. Compared to the VKA group, the DOAC group displayed a significant lower risk of all-cause death [RR (95%CI): 0.44 (0.35-0.55)]. Meanwhile, DOAC therapy group was similar to VKA therapy in reducing ischemic stroke [RR (95%CI): 0.65 (0.33-1.28)] and thromboembolic events [RR (95%CI): 0.95 (0.74-1.22)]. The incidence of major bleeding [RR (95%CI): 0.69 (0.44-1.07)] were comparable between the two groups. Conclusion In patients with HCM and AF, DOAC therapy were superior or non-inferior to VKA therapy in reducing the risk of all-cause death and thromboembolic events, without increasing bleeding risk. Further RCTs are needed to provide more evidence for DOAC therapy in this population.Efficacy and safety endpoints in DOAC th