Zanubrutinib-lenalidomide-rituximab (ZR2) in unfit diffuse large B-cell lymphoma: efficient and tolerant.

The objective of this study is to examine the effectiveness and safety of zanubrutinib, rituximab, and lenalidomide (ZR2) in unfit patients with diffuse large B-cell lymphoma (DLBCL). Thrombosis or bleeding risk of ZR2 regimen, especially when antiplatelet agents were co-prescribed, was also evaluated. We retrospectively reviewed unfit newly diagnosed (ND) and refractory or relapsed (R/R) patients with DLBCL who were administered with ZR2 regimen in two medical centers between December 2019 and February 2022. Response rates, progression-free survival (PFS), overall survival (OS), bleeding adverse events (AEs), and thrombosis episodes were analyzed. Furthermore, we investigated the effects of zanubrutinib alone or in combination with lenalidomide on platelet functions in vitro and in vivo. A total of 30 unfit patients (13 ND DLBCL and 17 R/R DLBCL patients) who received ZR2 regimen were enrolled in the study (median age: 69.5 years). The ultimate ORRs for the ND DLBCL and R/R DLBCL were 77.0% and 50.1%, respectively. The median follow-up was 16.6 months. The median PFS and OS were not achieved during the follow-up time. Subcutaneous hemorrhage AEs occurred in four cases, three cases suffered severe bleeding events, and thrombosis events were observed in two patients. ZR2 regimen inhibited platelet functions (aggregation, clot retraction, spreading and activation) in vitro and in vivo function testing especially in response to collagen. ZR2 is an efficient treatment option for unfit patients with DLBCL and could be well tolerated. Notably, this regimen inhibited platelet functions. Antiplatelet agents should be used with caution in patients treated with this regimen.

Risk-based and individualised management of bleeding and thrombotic events in adults with primary immune thrombocytopenia (ITP).

Although bleeding is one of the main symptoms of primary immune thrombocytopenia (ITP), risk factors for bleeding have yet to be fully established. Low platelet count (PC; <20-30 × 109 /L) is generally indicative of increased risk of bleeding. However, PC and bleeding events cannot be fully correlated; many other patient- and disease-related factors are thought to contribute to increased bleeding risk. Furthermore, even though ITP patients have thrombocytopenia and are at increased risk of bleeding, ITP also carries higher risk of thrombotic events. Factors like older age and certain ITP treatments are associated with increased thrombotic risk. Women's health in ITP requires particular attention concerning haemorrhagic and thrombotic complications. Management of bleeding/thrombotic risk, and eventually antithrombotic therapies in ITP patients, should be based on individual risk profiles, using a tailored, patient-centric approach. Currently, evidence-based recommendations and validated tools are lacking to support decision-making and help clinicians weigh risk of bleeding against thrombosis. Moreover, evidence is lacking about optimal PC for achieving haemostasis in invasive procedures settings. Further research is needed to fully define risk factors for each event, enabling development of comprehensive risk stratification approaches. This review discusses risk-based and individualised management of bleeding and thrombosis risk in adults with primary ITP.

Clopidogrel with indobufen or aspirin in minor ischemic stroke or high-risk transient ischemic attack: a randomized controlled clinical study.

BACKGROUND: Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases. OBJECTIVE: The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA. METHODS: An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset. RESULTS: We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874-7.036, P < 0.0001). Although the improvement rate of NIHSS score in the indobufen and clopidogrel group was higher than that in the aspirin and clopidogrel group, the difference was not statistically significant (P > 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035). CONCLUSION: The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021).

Comparative Data of Procedural and Midterm Outcomes in Patients Who Underwent Percutaneous Left Atrial Appendage Closure Between the WATCHMAN FLX and WATCHMAN 2.5 Devices　- Insight From the OCEAN-LAAC Registry.

BACKGROUND: Limited data are available regarding clinical outcomes after percutaneous left atrial appendage closure using WATCHMAN FLX (WM-FLX) and WATCHMAN-2.5 (WM2.5) devices in Asian patients. METHODS AND RESULTS: Data of 1,464 consecutive patients (WM-FLX, n=909; WM2.5, n=555) were extracted from a Japanese multicenter registry, and clinical data were compared between the 2 groups. No in-hospital deaths, periprocedural stroke, or device embolization occurred. Procedural success was significantly higher in the WM-FLX than WM2.5 group (95.8% vs. 91.9%; P=0.002) owing to the lower incidence of periprocedural pericardial effusion (0.55% vs. 1.8%; P=0.021). No significant differences in all-cause death, postprocedural stroke, and device-related thrombus were observed between the 2 groups. However, the cumulative bleeding rate at 1 year was substantially lower in the WM-FLX group (7.8% vs. 16.4%; P<0.001). Landmark analysis of bleeding events highlighted lower bleeding rates in the WM-FLX than WM2.5 group within the first 6 months (6.4% vs. 14.8%; P<0.001), with comparable bleeding rates over the 6- to 12-month period (1.5% vs. 3.2%, respectively; P=0.065). CONCLUSIONS: This study demonstrated higher early safety and lower 1-year bleeding rates in the WM-FLX than WM2.5 group. The lower bleeding events with WM-FLX are likely due to multiple factors other than purely difference in devices, such as postprocedural drug regimen.

Factor XI/XIa inhibitors for the prevention and treatment of venous and arterial thromboembolism: A narrative review.

During the past decade, direct oral anticoagulants (DOACs) have advanced and simplified the prevention and treatment of venous thromboembolism (VTE). However, there remains a high incidence of bleeds, which calls for agents that have a reduced risk of bleeding. Factor XI (FXI) deficiency is associated with lower rates of venous thrombosis and stroke compared to the general population with a lower risk of bleeding. In conjunction with this, phase 2 studies have demonstrated safety and the potential for reduced thrombotic events with FXI inhibitors as compared to currently available medications. The aim of this review is to summarize key data on the clinical pharmacology of FXI, the latest developments in clinical trials of FXI inhibitors, and to describe the efficacy and safety profiles of FXI inhibitors for the prevention of venous and arterial thromboembolism.

Air pollution and serious bleeding events in high-risk older adults.

IMPORTANCE: Despite biological plausibility, very few epidemiologic studies have investigated the risks of clinically significant bleeding events due to particulate air pollution. OBJECTIVE: To measure the independent and synergistic effects of PM2.5 exposure and anticoagulant use on serious bleeding events. DESIGN: Retrospective cohort study (2008-2016). SETTING: Nationwide Medicare population. PARTICIPANTS: A 50% random sample of Medicare Part D-eligible Fee-for-Service beneficiaries at high risk for cardiovascular and thromboembolic events. EXPOSURES: Fine particulate matter (PM2.5) and anticoagulant drugs (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin). MAIN OUTCOMES AND MEASURES: The outcomes were acute hospitalizations for gastrointestinal bleeding, intracranial bleeding, or epistaxis. Hazard ratios and 95% CIs for PM2.5 exposure were estimated by fitting inverse probability weighted marginal structural Cox proportional hazards models. The relative excess risk due to interaction was used to assess additive-scale interaction between PM2.5 exposure and anticoagulant use. RESULTS: The study cohort included 1.86 million high-risk older adults (mean age 77, 60% male, 87% White, 8% Black, 30% anticoagulant users, mean PM2.5 exposure 8.81 µg/m3). A 10 µg/m3 increase in PM2.5 was associated with a 48% (95% CI: 45%-52%), 58% (95% CI: 49%-68%) and 55% (95% CI: 37%-76%) increased risk of gastrointestinal bleeding, intracranial bleeding, and epistaxis, respectively. Significant additive interaction between PM2.5 exposure and anticoagulant use was observed for gastrointestinal and intracranial bleeding. CONCLUSIONS: Among older adults at high risk for cardiovascular and thromboembolic events, increasing PM2.5 exposure was significantly associated with increased risk of gastrointestinal bleeding, intracranial bleeding, and epistaxis. In addition, PM2.5 exposure and anticoagulant use may act together to increase risks of severe gastrointestinal and intracranial bleeding. Thus, clinicians may recommend that high-risk individuals limit their outdoor air pollution exposure during periods of increased PM2.5 concentrations. Our findings may inform environmental policies to protect the health of vulnerable populations.

Direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) for extended thromboprophylaxis following major abdominal/pelvic cancer-related surgery: a systematic review and meta-analysis.

BACKGROUND: The use of direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparin (LMWH) for extended thromboprophylaxis of abdominal/pelvic cancer-related postoperative thromboembolism (VTE) is unclear. We aim to investigate the efficacy and safety of DOACs vs. LMWH in these patients. METHODS: A systematic review was conducted using EMBASE, MEDLINE, CENTRAL, and Web of science through May 19th, 2023 for all randomized controlled trials (RCTs) and observational studies that compared the outcomes with DOACs vs. LMWH for extended thromboprophylaxis among patients undergoing abdominal/pelvic cancer surgery. Primary efficacy outcome was clinical VTE, and safety outcome was clinically relevant bleeding complications reported within the 30-day postoperative period. This study was registered in PROSPERO (CRD42023413175). RESULTS: We identified 5078 articles and selected 29 full-text articles for eligibility. A total of 9 studies (2 RCTs and 7 observational studies) encompassing 2651 patients were included for systematic review and 7 for meta-analysis. When compared with LMWH extended thromboprophylaxis, DOACs had a similar incidence of VTE (RR: 0.65 [95% CI: 0.32-1.33], I2 = 0%), major bleeding (RR: 1.68 [95% CI: 0.36-7.9], I2 = 26%), and clinically relevant non-major bleeding (RR: 0.68 [95% CI: 0.39-1.19], I2 = 0%). Subgroup analysis suggested no difference according to the study type (RCTs versus observational studies) regarding clinical VTE or major bleeding (Pinteraction = 0.43 and Pinteraction = 0.71, respectively). CONCLUSION: Our results suggest that DOACs for extended thromboprophylaxis were an effective and safe alternative to LMWH after major abdominal/pelvic cancer-related surgery.

IL-10 plus the EASIX score predict bleeding events after anti-CD19 CAR T-cell therapy.

Chimeric antigen receptor (CAR) T-cell-associated coagulopathy can cause bleeding events. To explore risk factors for hemorrhage after CAR T-cell therapy, we retrospectively analyzed routine indicators in 56 patients with non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia who received anti-CD19 CAR T-cell therapy. Disturbance of coagulation occurred mainly within one month post infusion, especially on day 7 and 14. The cumulative incidence of bleeding events within one month was 32.8%, with the median onset of 7 (range, 0-28) days. All bleeding events were grade 1-3. Patients who experienced bleeding events within one month had longer prothrombin time, higher IL-6, higher IL-10, and lower platelets before lymphodepletion. There were also correlations among coagulation-, inflammatory-, and tumor burden-related markers. Multi-variate analysis showed IL-10 (> 7.98 pg/mL; adjusted odds ratio [OR], 13.84; 95% confidence interval [CI], 2.03-94.36; P = 0.007) and the endothelial activation and stress index (EASIX, defined as dehydrogenase [U/L] × creatinine [mg/dL] / platelets [×109 cells/L]; >7.65; adjusted OR, 7.06; 95% CI, 1.03-48.23; P = 0.046) were significant risk factors for bleeding events. IL-10 plus the EASIX defined three risk groups for bleeding events with cumulative incidence of 100% (hazard ratio [HR], 14.47; 95% CI, 2.78-75.29; P < 0.0001), 38.5% (HR, 3.68; 95% CI, 0.82-16.67; P = 0.089), and 11.8% (reference), respectively. Future studies are needed to verify the risk assessment models for bleeding events after CAR T-cell treatment in larger cohorts.

Relationship between coronary artery calcium score and bleeding events after percutaneous coronary intervention in chronic coronary syndrome.

The relationship between coronary artery calcium (CAC) and bleeding events after percutaneous coronary intervention (PCI) in patients with chronic coronary syndrome (CCS) is not well established. This study aimed to examine the association between CAC scores and clinical outcomes after PCI in patients with CCS. This retrospective observational study included 295 consecutive patients who underwent multidetector computer tomography and were scheduled for their first elective PCI. Patients were categorized into two groups based on the CAC scores (low: ≤ 400 or high: > 400). The bleeding risk was evaluated using the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. The primary clinical outcome was a major bleeding event within 1 year after PCI, defined as Bleeding Academic Research Consortium (BARC) 3 or 5. The high CAC score group had a higher proportion of patients meeting the ARC-HBR criteria than the low CAC score group (52.7% vs. 31.3%, p < 0.001). Kaplan-Meier survival analysis showed that the incidence of major bleeding events was higher in the high CAC score group as compared to the low CAC score group (p < 0.001). Furthermore, multivariate Cox regression anal ysis revealed that a high CAC score was an independent determinant of major bleeding events during the first year after PCI. A high CAC score is significantly associated with the incidence of major bleeding events after PCI in CCS patients.

Predictive values of baseline matrix metalloproteinase 9 levels in peripheral blood on 3-month outcomes of high-risk patients with minor stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: To explore the relationship between baseline levels of matrix metalloproteinase 9 (MMP9) in peripheral blood and the outcomes in patients with acute minor stroke and transient ischemic attack (TIA). METHODS: We assessed data from patients with acute minor ischemic stroke or TIA who were included in the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial. Baseline level of MMP9 in peripheral blood is classified into five quintiles. We assessed the relationship between the baseline MMP9 and outcomes of stroke recurrence, composite vascular events, and poor functional outcomes within 90 days after stroke onset. RESULTS: Of the 3014 patients included, 295 (9.79%) had recurrent stroke, 289 (9.59%) had recurrent ischemic stroke, 297 (9.85%) had combined vascular events, and 199 (6.64%) had poor functional outcomes within 90 days. We used MMP9 concentrations near hazard ratio (HR) = 1 (Q3) in restricted cubic splines as the reference. The result showed that, compared to patients in the Q3 group, patients in the highest quintile (Q5 group) had an increased risk of poor functional outcomes at 90 days after adjusting the risk factors and confounders (p = 0.030), which may be associated with an increased risk of combined vascular events (p = 0.052). Using Cox regression models or logistic regression models with restricted cubic spline, we also observed that higher MMP9 ratios were associated with an increased risk of stroke recurrence, combined events, and poor functional outcomes at a range of concentrations. CONCLUSIONS: For patients with acute minor stroke or TIA, higher baseline MMP9 level was associated with an increased risk of poor functional outcomes, which might be related to stroke recurrence and combined vascular events.

Association between ticagrelor plasma concentration and bleeding events in Chinese patients with acute coronary syndrome.

AIMS: The risk of ticagrelor-related bleeding events remains a major clinical concern, especially in East Asian populations. Previous studies have reported higher ticagrelor exposure in Asian patients than in Caucasians. This prompted us to investigate the correlation between ticagrelor concentrations and bleeding events. METHODS: Patients diagnosed with acute coronary syndrome and receiving dual antiplatelet therapy (aspirin and ticagrelor) were enrolled and followed up for 12 months. Trough plasma concentrations of ticagrelor and a major active metabolite were assayed, and 10 single nucleotide polymorphisms associated with ticagrelor pharmacokinetics and safety were also identified. RESULTS: A total of 631 patients were included and 133 patients had bleeding academic research consortium type 1 or 2 bleeding event. The median ticagrelor concentration (interquartile range) was significantly higher in patients with bleeding events than that in patients without bleeding events (322.6 ng/mL [196.2-458.0 ng/mL] vs. 222.1 ng/mL [140.4-341.9 ng/mL], P < .001). According to the receiver operating characteristic curve, the cut-off value for ticagrelor levels predicting bleeding events was 363.3 ng/mL (area under the curve = 0.65; P < .001, 95% Cl: 0.595-0.700). Pharmacogenomics results showed that P2Y12 (rs6787801, P = .024) and P2Y12 (rs6785930, P = .048) were statistically associated with ticagrelor levels and bleeding events, respectively. CONCLUSION: Ticagrelor plasma concentrations were associated with bleeding events in Chinese patients with acute coronary syndrome.

Association between liver fibrosis and thrombotic or bleeding events in acute coronary syndrome patients.

BACKGROUND: The prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome. METHODS: We included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS). RESULTS: During the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (all p < 0.05). The positive relationship between LFS and MACCE was consistent in different subgroups. CONCLUSIONS: In ACS patients, increased LFS predicted an elevated risk of thrombotic events but not bleeding. LFS may contribute to thrombotic risk stratification after ACS.

Intracranial hemorrhage in COVID-19 patients during extracorporeal membrane oxygenation for acute respiratory failure: a nationwide register study report.

BACKGROUND: In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID). METHODS: The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites. FINDINGS: The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency. INTERPRETATION: Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.

Bleeding events in the emergency department with warfarin versus novel oral anticoagulants: A five-year analysis.

Background: Although warfarin is the most effective treatment approved to prevent atrial fibrillation-associated stroke, it remains underused in clinical practice due to patient noncompliance. Therefore, novel oral anticoagulants (NOACs) have been developed. Aims: This study aimed to identify bleeding complications in patients who were taking oral anticoagulants and compare the rates of major and minor bleeding events between NOACs and warfarin groups. Patients and Methods: We conducted a retrospective, observational study of warfarin- and NOAC-treated patients who presented to an emergency department between January 2015 and December 2019 with bleeding events. We compared patients with major and minor bleeding in terms of age, gender, comorbid diseases, type of anticoagulant, and site of bleeding. Results: An electronic search yielded 95 (21.9%) cases of patients taking a NOAC (i.e., dabigatran [19], rivaroxaban [45], apixaban [29], or edoxaban [6]) and 354 taking warfarin. There were no significant differences between the warfarin and NOACs groups in the frequency of minor bleeding complications. Similarly, there were no significant differences between the groups in the frequency of major bleeding complications. No significant difference in intracranial bleeding was seen between the NOACs- and warfarin-treated patients, although the incidence of gastrointestinal bleeding was significantly higher in the NOACs (P = 0.102 and P = 0.021, respectively). Conclusion: Our findings indicate that rates of major and minor bleeding complications in patients taking NOACs are similar to those in patients taking warfarin. While warfarin was associated with fewer complications than NOACs in terms of gastrointestinal bleeding, the risk of intracranial bleeding, was similar between the groups.

Mid-term outcomes of modified valve-sparing aortic root replacement versus the Bentall procedure for middle-aged Chinese patients with acute DeBakey I aortic dissection: a single-center retrospective study.

BACKGROUND: The mid-term and long-term efficacies of valve preservation in acute DeBakey I aortic dissection (AD) are controversial. Thus, it is unclear whether middle-aged patients with acute DeBakey I AD should undergo modified valve-sparing procedures or the Bentall procedure in an emergency setting. METHODS: This study included 213 middle-aged Chinese patients (under 60 years old) who were treated for acute DeBakey I AD between January 2009 and June 2015. The treatments involved modified valve-sparing aortic root replacement (VSARR) (117 patients) or the Bentall procedure (96 patients). Preoperative, intraoperative, postoperative, and follow-up data were analyzed. Echocardiography and thoracoabdominal computed tomography angiography (CTA) findings were reviewed at 3 months, 1 year, and then annually after surgery. RESULTS: No significant differences were observed in terms of the preoperative, intraoperative, in-hospital mortality, and postoperative parameters. There were also no significant differences in aortic regurgitation (AR). However, follow-up examinations using CTA revealed that 6 patients had endoleakage at the distal end of the triple-branched stent (0/110 patients [0.0%] vs. 6/90 patients [6.7%], P = 0.022). The anticoagulation-related thromboembolism/bleeding events was significantly lower in group A than in group B (0/110 patients [0.0%] vs. 11/90 patients [11.1%], P = 0.001). And postoperative aortic valve re-operation rate was significantly lower in group A (1/110 patients [0.9%] vs. 8/90 patients [8.9%], P = 0.020). There was no significant difference in survival during the follow-up period (log-rank P > 0.05). CONCLUSION: For middle-aged patients with acute DeBakey I AD, VSARR were associated with a lower rate of endoleakage at the distal end of the triple-branched stent, thromboembolism/bleeding events and aortic valve re-operation (vs. the Bentall procedure).

Bleeding events and mid-term mortality in the patients undergoing endovascular interventions for peripheral artery disease of the lower limbs based on the academic research consortium high bleeding risk criteria.

This study applied the Academic Research Consortium for HBR (ARC-HBR) criteria to peripheral artery disease (PAD) patients after Endovascular therapy (EVT) and assessed the prevalence of HBR, as well as the association between HBR and clinical outcomes. This is a single-center, non-randomized, controlled, and retrospective study. EVTs for symptomatic PAD are minimally invasive and efficient. Although bleeding can be a serious adverse event, the criteria for HBR and assessment of bleeding events in patients who underwent EVT have been limited. A total of 156 patients with PAD who underwent EVT were divided into two groups according to ARC-HBR criteria. The associations between HBR and bleeding events, which was defined as Bleeding Academic Research Consortium Type 3 or Type 5 bleeding within 1 year and all-cause mortality within 1 year, were analyzed. The percentage of patients who were categorized as having HBR was 75.0%. Bleeding events occurred in 12.6% of the patients. All bleeding events occurred in the HBR group, while no bleeding events occurred in the no-HBR group. (16.9% vs. 0.0%, respectively; p = 0.008). During the follow-up period, 11.1% of the patients had died. All-cause mortality was significantly higher in the HBR group than in the no-HBR group (14.7% vs. 0.0%, respectively; p = 0.019). Most patients with PAD were classified as having HBR as assessed by ARC-HBR criteria, and patients with HBR were at a higher risk of not only bleeding events but also mid-term mortality compared to those without HBR. ARC-HBR criteria can be a helpful parameter when treating PAD patients after EVT.

Impact of the clinical frailty scale on clinical outcomes and bleeding events in patients with ST-segment elevation myocardial infarction.

The Clinical Frailty Scale (CFS) is a simple tool to assess patients' frailty and may help to predict adverse outcomes in elderly patients. The aim of the present study was to examine the impact of CFS on clinical outcomes and bleeding events after successful percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI). We enrolled 266 consecutive patients with STEMI who underwent primary PCI in between January 2015 and June 2018. Patients were categorized into two groups based on the CFS stages: CFS 1-3 and CFS ≥ 4. We collected the data and evaluated the relationship between the CFS grade and the incidence of major adverse cardiovascular events (MACE) and Bleeding Academic Research Consortium 3 or 5 bleeding events. Of these patients, CFS ≥ 4 was present in 59 (22.2%). During the follow-up, 37.3% in the CFS ≥ 4 group and 8.2% in the CFS 1-3 group experienced MACE. In Kaplan-Meier analysis, the proportion of MACE-free survival for 4 years was significantly lower in the CFS ≥ 4 group (log-rank P < 0.001). Additionally, the proportion of bleeding event-free survival was significantly lower in the CFS ≥ 4 group (log-rank P < 0.001). The CFS (per 1-grade increase) remained an independent significant predictor of MACE on multivariate Cox proportional hazard analysis [hazard ratio 1.39 (95% confidence interval: 1.08 to 1.79, P = 0.01)]. In conclusion, CFS was an independent predictor of future adverse cardiac events in patients with STEMI. Therefore, the assessment of CFS is crucial in this population.

Combined with ticagrelor, 50 mg aspirin daily can reduce bleeding events without increasing ischemic risk compared with 75-100 mg aspirin daily in coronary artery disease patients: insights from the TIFU (Ticagrelor in Fuwai Hospital) study.

Patients treated with ticagrelor and aspirin usually suffer from bleeding events, especially mild bleeding which is one of the main factors reducing patients' adherence to ticagrelor. The objective of this study is to investigate the efficacy and safety of ticagrelor combined with a lower dose of aspirin (50 mg) than that recommended by guidelines (75-100 mg). In this study, we prospectively enrolled 1220 patients who take ticagrelor in the hospital. After excluding the patients who did not take ticagrelor after discharge or lost to follow-up, the remaining 1066 patients were divided into two aspirin dose groups: 75-100 mg (n = 744) and 50 mg (n = 322). The rates of major adverse cardiovascular events (MACEs), bleeding events and ticagrelor adherence were compared between the two groups. MACEs risk was not significantly different between the two groups (OR = 0.563, 95% CI: 0.244-1.300, P = .179). However, 50 mg aspirin was associated with a lower risk of any Bleeding Academic Research Consortium (BARC) bleeding events (OR = 0.605, 95% CI: 0.399-0.713, P = .001), also lower BARC bleeding events (OR = 0.639, 95% CI: 0.468-0.872, P = .005). Moreover, lower-dose aspirin was associated with a lower rate of ticagrelor withdrawal (OR = 0.459, 95% CI: 0.279-0.754, P = .002), mainly because of the decrease in ticagrelor withdrawal due to bleeding (OR = 0.378, 95% CI: 0.156-0.916, P = .031). After propensity score matching (PSM), a total of 317 patients in each group were matched. The MACEs composite was not significantly different between the two matched groups and 50 mg aspirin was associated with a lower risk of bleeding events and low ticagrelor withdrawal before and after multivariate adjustment. In conclusion, among patients who took ticagrelor (90 mg twice daily), 50 mg aspirin daily is associated with a lower rate of bleeding events and ticagrelor withdrawal but does not increase the MACE risk compared with 75-100 mg aspirin daily.

Impact of bleeding events after percutaneous coronary intervention in patients on hemodialysis.

Coronary artery disease is common in patients on dialysis; there is a high rate of bleeding events after percutaneous coronary intervention (PCI) in such patients. We investigated the impact of bleeding events after PCI on mortality in patients on hemodialysis. We included 386 consecutive hemodialysis patients who underwent PCI using a drug-eluting stent (DES) between September 2004 and December 2017 in our hospital, and investigated the impact of bleeding events on all-cause mortality after PCI. Bleeding events were assessed by the Thrombolysis in Myocardial Infarction (TIMI) bleeding definition within 24 months after PCI. A total of 42 patients experienced bleeding events. Of these, 30 patients (71.4%) had TIMI major bleeding events and 12 patients (28.6%) had TIMI minor bleeding events. Patients with bleeding events had significantly higher mortality than patients without bleeding events (survival rate, 55.1% vs 81.5%, log-rank: p < 0.001). These results suggest that bleeding events after PCI with a DES are notably associated with all-cause mortality among patients on hemodialysis. This is the first report about relationship between bleeding events and mortality to focus on patients on hemodialysis.

Persistence, effectiveness and safety of dabigatran in "real-world" Chinese patients with nonvalvular atrial fibrillation.

The purpose of this study is to provide detailed data on treatment persistence and clinical outcomes in Chinese patients with nonvalvular atrial fibrillation (NVAF). A single-center retrospective observational study was conducted. A total of 26,663 NVAF patients were enrolled from January 1, 2014 to December 31, 2017, clinical information of whom were from inpatient and outpatients data system was collected. The 1-year treatment persistence rates of 11,350 dabigatran users were 24.5% in 2014, 36.6% in 2015, 37.7% in 2016 and 51.8% in 2017. The predominant reason of non-persistence patients was the cost of treatment. Incidence rates of all-cause death, ischemic stroke and embolism were 1.99/100 person-years, 2.56/100 person-years and 0.77/100 person-years, respectively. Incidence rates of minor bleeding events, intracranial hemorrhage and gastrointestinal hemorrhage were 10.05/100 person-years, 0.51/100 person-years and 0.85/100 person-years, respectively. In conclusion, it is of importance for Chinese clinicians to know about these information because dabigatran is a relatively new drug in China. Compared with other reported data, patients of this study have (1) lower dabigatran persistence and lower incident rates of all-cause death, systemic embolism, minor bleeding events and gastrointestinal hemorrhage and (2) higher incident rates of ischemic stroke and intracranial hemorrhage.