Feasibility of atezolizumab and bevacizumab combination regimens in patients with hepatocellular carcinoma and lung cancer taking direct oral anticoagulants.

AIM: Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore, combining Atezo/Bev regimens with DOACs may exacerbate the bleeding risk. This study investigated the feasibility of the Atezo/Bev regimen in patients taking DOACs. METHODS: This retrospective study included 141 patients with unresectable hepatocellular carcinoma (HCC) or advanced lung cancer (LC) treated with Atezo/Bev regimens. Patients who used antithrombotic agents other than DOACs were excluded. Bleeding events during the Atezo/Bev regimen were analyzed. RESULTS: The incidence rates of bleeding of any grade in the DOAC (n = 11) and no antithrombotic agent (NAA) (n = 130) groups were 9.1% and 10.8%, respectively, with no significant differences. Moreover, no significant difference was found in the frequency of bleeding of grade ≥3 between the DOAC and NAA groups. No patients in the DOAC group discontinued the Atezo/Bev regimen because of severe bleeding. Although serum albumin levels, with a hazard ratio (HR) of 0.298 (95% confidence interval [CI]: 0.105-0.847), independently contributed to bleeding events (p = 0.023), DOAC administration did not (HR: 1.357; 95% CI: 0.157-10.54; p = 0.770). Among only patients with HCC (n = 59), none of the five patients taking DOACs experienced bleeding events. A high albumin-bilirubin score (HR: 9.083, 95% CI: 1.118-73.76) was associated with bleeding events (p = 0.039). CONCLUSIONS: DOACs did not have a considerable effect on bleeding events in the Atezo/Bev regimens for HCC or LC. Under careful surveillance for bleeding, Atezo/Bev regimens may be feasible in patients receiving DOACs.

Clinical outcomes of adjusted-dose versus standard-dose prasugrel in East Asian patients with acute myocardial infarction.

BACKGROUND: The comparative efficacy and safety of adjusted- and standard-dose prasugrel in East Asian patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) remain unclear. This study aimed to comparatively assess the ischaemic and bleeding outcomes of adjusted-dose (maintenance dose: 3.75 mg) and standard-dose (maintenance dose: 10 mg) prasugrel in East Asian patients with AMI undergoing PCI. METHODS: From a combined dataset sourced from nationwide AMI registries in Japan and South Korea (n = 17,118), patients treated with either adjusted- or standard-dose prasugrel were identified. Patients who did not undergo emergent PCI, those on oral anticoagulants, and those meeting the criteria of contraindication of prasugrel in South Korea (age ≥ 75 years, body weight < 60 kg, or history of stroke) were excluded. Major adverse cardiovascular events (MACE) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding events were compared between the adjusted-dose (n = 1160) and standard-dose (n = 1086) prasugrel groups. RESULTS: Within the propensity-matched cohort (n = 702 in each group), no significant difference was observed in the in-hospital MACE between the adjusted- and standard-dose prasugrel groups (1.85% vs. 2.71%, odds ratio [OR] 0.68, 95% confidence interval [CI] 0.33-1.38, p = 0.286). However, the incidence of in-hospital major bleeding was significantly lower in the adjusted-dose prasugrel group than in the standard-dose group (0.43% vs. 1.71%, OR 0.25, 95% CI 0.07-0.88, p = 0.031). The cumulative 12-month incidence of MACE was equivalent in both groups (4.70% vs. 4.70%, OR 1.00, 95% CI 0.61-1.64, p = 1.000). CONCLUSIONS: Among East Asian patients with AMI undergoing PCI, those administered adjusted-dose prasugrel exhibited a lower risk of in-hospital bleeding events than those administered standard-dose prasugrel, while maintaining a comparable 1-year incidence of MACE.

Dual antiplatelet therapy for ischemic stroke with intracranial arterial stenosis: a systematic review and meta-analysis.

Background: The safety and efficacy of dual antiplatelet therapy (DAPT) in ischemic stroke patients with intracranial artery stenosis (ICAS) remain contentious. Aims: This study evaluates DAPT's effectiveness and safety for these patients. Methods: This review was reported following PRISMA 2020 guidelines. A comprehensive search was conducted in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, WanFang, VIP, and SinoMed up to June 20, 2023, for randomized controlled trials comparing efficacy and safety of DAPT against single antiplatelet therapy (SAPT) in ischemic stroke patients with ICAS. The primary outcome was a composite of ischemic and bleeding events. Secondary outcomes included stroke (cerebral infarction and hemorrhage), ischemic events, and cerebral infarction. Safety outcomes assessed were bleeding events, cerebral hemorrhage, and mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were synthesized using Review Manager 5.4. Results: Analysis of 21 randomized controlled trials involving 3,591 patients revealed that DAPT significantly lowered the rate of ischemic and bleeding events (RR = 0.52; 95% CI: 0.46-0.59, p < 0.001) and recurrent stroke (RR = 0.37; 95% CI: 0.30-0.44, p < 0.001) compared to SAPT. There was no significant increase in bleeding events (RR = 1.34; 95% CI: 0.97-1.85, p = 0.07) or cerebral hemorrhage (RR = 0.47; 95% CI: 0.17-1.31, p = 0.15). Conclusion: DAPT proveed to be effective and safe for ischemic stroke patients with ICAS and significantly reduced stroke and the composite endpoint of ischemic and bleeding events without elevating bleeding risks.

Thromboembolic events after major bleeding events in patients with mechanical heart valves: a 13-year analysis.

Anticoagulation in patients with mechanical heart valves (MHV) is associated with a risk of major bleeding episodes (MBE). In case of MBE, anticoagulant interruption is advocated. However, there is lack of data regarding the thrombo-embolic events (TE) risk associated with anticoagulant interruption. The main objective of the study was to evaluate the rate and risk factors of 6-months of TEs in patients with MHV experiencing MBE. This observational study was conducted over a 13-year period. Adult patients with a MHV presenting with a MBE were included. The main study endpoint was 6-month TEs, defined by clinical TEs or an echocardiographic documented thrombosis, occurring during an ICU stay or within 6-months. Thromboembolic events were recorded at ICU discharge, and 6 months after discharge. Seventy-nine MBEs were analysed, the rate of TEs at 6-months was 19% CI [11-29%]. The only difference of presentation and management between 6-month TEs and free-TE patients was the time without effective anticoagulation (TWA). The Receiver Operator Characteristic curve identified the value of 122 h of TWA as a cut-off. The multivariate analysis identified early bleeding recurrences (OR 3.62, 95% CI [1.07-12.25], p = 0.039), and TWA longer than 122 h (OR 4.24, 95% CI [1.24-14.5], p = 0.021), as independent risk factors for 6-month TEs. A higher rate of TE was associated with anticoagulation interruption longer than 5 days and early bleeding recurrences. However, the management should still be personalized and discussed for each case given the heterogeneity of causes of MBE and possibilities of haemostatic procedures.

Comparison of Discriminative Ability of Bleeding Risk Criteria and Scores for Predicting Short- and Mid-Term Major Bleeding Events in Patients Undergoing Percutaneous Coronary Intervention.

Background: This study aimed to compare the discriminative ability of the Japanese Version of High Bleeding Risk (J-HBR), Academic Research Consortium for High Bleeding Risk (ARC-HBR), and Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) scores for predicting major bleeding events. Methods and Results: Between January 2017 and December 2020, 646 consecutive patients who underwent successful percutaneous coronary intervention (PCI) were enrolled. We scored the ARC-HBR and J-HBR criteria by assigning 1 point to each major criterion and 0.5 point to each minor criterion. The primary outcome was major bleeding events, defined as Bleeding Academic Research Consortium type 3 or 5 bleeding events. According to the J-HBR, ARC-HBR, and PRECISE-DAPT scores, 428 (66.3%), 319 (49.4%), and 282 (43.7%) patients respectively had a high bleeding risk. During the follow-up period (median, 974 days), 44 patients experienced major bleeding events. The area under the curve (AUC) using the time-dependent receiver operating characteristic curve for major bleeding events was 0.84, 0.82, and 0.83 within 30 days and 0.86, 0.83, and 0.80 within 2 years for the J-HBR, ARC-HBR, and PRECISE-DAPT scores, respectively. The AUC values did not differ significantly among the 3 bleeding risk scores. Conclusions: The J-HBR score had a discriminative ability similar to the ARC-HBR and PRECISE-DAPT scores for predicting short- and mid-term major bleeding events.

Impact of renal function on adverse bleeding events associated with dual antiplatelet therapy in patients with acute coronary syndrome.

It is believed, but not well established, that renal dysfunction increases the risk of adverse bleeding events associated with dual antiplatelet therapy (DAPT), especially in patients with acute coronary syndrome (ACS). The aim of this study is to estimate the impact of renal function on adverse bleeding events associated with DAPT in patients with ACS. A total of 1,264 ACS patients who received DAPT, clopidogrel (n = 530) or prasugrel (n = 734) in addition to aspirin, were assessed in a multicenter observational study. The relationship between renal function and bleeding event, defined as BARC 3 or 5, was determined using a marginal effect from the logit model and Royston-Parmar model. During an average 313.1 days of the observation period, defined as the duration of DAPT after admission until the implementation of a change in the regimen, bleeding events were observed in 7.4% of patients (n = 94). The estimated curves demonstrated that the probability of bleeding was positive correlated with renal dysfunction (6.0 to 8.6), regardless of the DAPT regimen used. This probability was consistently higher in clopidogrel (7.4 to 10.5) than in prasugrel (4.8 to 0.7). This trend was also shown in maintenance hemodialysis patients (6.7 vs. 10.3). Estimated cumulative incidences among individual stages of renal function were drawn. In conclusion, bleeding events increased with worsening renal function, and prasugrel is safer than clopidogrel as a component of DAPT throughout all levels of renal function, including hemodialysis patients after ACS.

Direct Oral Anticoagulants Affect Activated Clotting Time During and Bleeding Events After Percutaneous Coronary Intervention.

Inappropriately high activated clotting time (ACT) during percutaneous coronary intervention (PCI) is associated with an increased risk of bleeding events. However, whether the prescription of direct oral anticoagulants (DOACs) affects ACT kinetics during heparin use and adverse clinical events in patients who underwent PCI remains unclear. We aimed to evaluate the relations between ACT changes during and adverse clinical events after PCI in patients who were prescribed DOAC. This observational study included 246 patients who underwent PCI at the 2 cardiovascular centers who were not receiving warfarin and whose ACT was recorded immediately before and 30 minutes after injection of unfractionated heparin. Patients were divided into 2 groups according to DOAC prescription at the time of the index PCI: DOAC users (n = 31) and nonusers (n = 215). Any bleeding and systemic thromboembolic events were investigated until 30 days after PCI. The average age of this population was 70.5 years, and 66.3% were male. Average ACT was significantly higher in DOAC users than nonusers both before and 30 minutes after unfractionated heparin induction (157.2 ± 30.1 vs 131.8 ± 25.1 seconds, p <0.001; 371.1 ± 122.2 vs 308.3 ± 82.2 seconds, p <0.001; respectively). The incidence of systemic thromboembolism after PCI was low and comparable between the 2 groups (0% vs 3.7%, p = 0.60). However, the rate of any bleeding event was significantly higher in DOAC users than in nonusers (16.1% vs 4.7%, p = 0.028). Patients receiving DOAC have higher ACT during PCI and higher incidence of bleeding events than those not receiving DOAC.

Antiplatelet and anticoagulant therapies in hereditary hemorrhagic telangiectasia: A large French cohort study (RETROPLACOTEL).

BACKGROUND: It is unclear whether hereditary hemorrhagic telangiectasia (HHT) patients can tolerate antithrombotic therapies (AT) including antiplatelet (AP) and/or anticoagulant (AC) agents. OBJECTIVES: Primary endpoint was tolerance to AT in HHT. Secondary endpoints were to identify factors associated with major bleeding events (MBE) and premature discontinuation of AT. METHODS: Retrospective multicenter study in French national HHT Registry patients exposed to AT. RESULTS: We included 126 patients with 180 courses of AT. Median follow-up was 24 [11-52] months. Mean age was 65.6 ± 13.1 years. The first 3 months of AT exposure had an increased risk of hospitalization for hemorrhage (p < 0.001) and transfusions (p < 0.001). MBE (n = 63) occurred more frequently in the first 3 months of AT exposure (p < 0.001). Premature discontinuation of AT occurred in 61 cases. Rate of premature discontinuation was 29 % under both AP and AT therapy but significantly higher under dual AP therapy (n = 4/7, 57 % p = 0.008). Risk factors for MBE were: age ≥ 60 years (HR 2.34 [1.12;4.87], p = 0.023), prior hospitalization in the 3 months before starting AT for hemorrhage (HR 3.59 [1.93;6.66], p < 0.001) or transfusion (HR 3.15 [1.61;6.18], p = 0.001), previous history of gastro-intestinal bleeding (HR 2.71 [1.57;4.65], p < 0.001) or MBE (HR 4.62 [2.68;7.98], p < 0.001). Frequency of MBE did not differ between groups except for a higher risk in the dual AP group (HR 3.92 [1.37;11.22], p = 0.011). CONCLUSION: Tolerance of AC or AP therapy was similar in HHT population but not dual AP therapy. We identified risk factors for MBE occurrence or premature discontinuation under AT.

Validation of Academic Research Consortium for High Bleeding Risk Definition in East-Asian Patients.

Background: Clinical applicability of the Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria in East-Asian patients receiving potent antiplatelet therapy for acute coronary syndromes (ACS) is still undetermined. Objectives: The purpose of this study was to validate the ARC definition for HBR in East-Asian patients with ACS for invasive management. Methods: We analyzed data from the TICAKOREA (Ticagrelor Versus Clopidogrel in Asian/Korean Patients With ACS Intended for Invasive Management) trial and randomly assigned 800 Korean ACS subjects to receive, in a 1:1 ratio, ticagrelor or clopidogrel. Patients were considered HBR if they met at least 1 major or 2 minor ARC-HBR criteria. The primary bleeding endpoint was Bleeding Academic Research Consortium 3 or 5 bleeding and the primary ischemic endpoint was a major adverse cardiovascular event (MACE) (a composite of cardiovascular death, myocardial infarction, or stroke) at 12 months. Results: Among 800 randomized patients, 129 (16.3%) were categorized HBR patients. HBR patients, compared with non-HBR patients, had a higher incidence of Bleeding Academic Research Consortium 3 or 5 bleeding (10.0% vs 3.7%; HR: 2.98; 95% CI: 1.52-5.86; P < 0.001) and MACE (14.3% vs 6.1%; HR: 2.35; 95% CI: 1.35-4.10; P = 0.002). The relative treatment effect of ticagrelor or clopidogrel on primary bleeding and ischemic outcomes were different between each group. Conclusions: This study validates the ARC-HBR definition in Korean ACS patients. Approximately 15% of patients qualified as HBR patients who were at increased risk not only for bleeding but also for thrombotic events. The clinical application of ARC-HBR to determine the relative effect of different antiplatelet regiments should be further investigated. (Safety and Efficacy of Ticagrelor Versus Clopidogrel in Asian/KOREAn Patients with Acute Coronary Syndromes Intended for Invasive Management [TICA KOREA]; NCT02094963).

Efficacy and safety of fondaparinux in preventing venous thromboembolism in Chinese cancer patients: a single-arm, multicenter, retrospective study.

Objective: Fondaparinux is a synthetic anticoagulant for the prevention of venous thromboembolism (VTE), and its administration in Chinese cancer patients is rarely reported. This study aimed to assess the efficacy and safety of fondaparinux in preventing VTE in Chinese cancer patients. Methods: A total of 224 cancer patients who received fondaparinux treatment were reviewed in this single-arm, multicenter, retrospective study. Meanwhile, VTE, bleeding, death, and adverse events of those patients in the hospital and at 1 month after treatment (M1) were retrieved, respectively. Results: The in-hospital VTE rate was 0.45% and there was no (0.00%) VTE occurrence at M1. The in-hospital bleeding rate was 2.68%, among which the major bleeding rate was 2.23% and the minor bleeding rate was 0.45%. Moreover, the bleeding rate at M1 was 0.90%, among which both the major and minor bleeding rates were 0.45%. The in-hospital death rate was 0.45% and the death rate at M1 was 0.90%. Furthermore, the total rate of adverse events was 14.73%, including nausea and vomiting (3.13%), gastrointestinal reactions (2.23%), and reduced white blood cells (1.34%). Conclusion: Fondaparinux could effectively prevent VTE with low bleeding risk and acceptable tolerance in cancer patients.

Spontaneous Prostatic Hemorrhage in a COVID-19 Patient: A Case Report.

Hematuria occurring in patients with acute kidney injury caused by Corona Virus Disease 2019 (COVID-19) infection has been reported. However, cases of macroscopic hematuria in COVID-19 patients leading to a severe decrease in hemoglobin have not been reported heretofore. Herein, we describe the case of a 56-year-old male patient who suffered from spontaneous prostatic hemorrhage caused by thrombocytopenia and coagulation dysfunction associated with COVID-19 infection, which manifested as macroscopic hematuria, bladder blood clot tamponade and severe hemoglobin decline. Prostatic hemorrhage was diagnosed by endoscopy. There was no recurrence of macroscopic hematuria after undergoing transurethral prostate electrocoagulation for hemostasis, infusing plasma to supplement coagulation factors and taking finasteride. One month after the bleeding event, the patient's blood routine reexamination revealed that the platelet count returned to the normal value and coagulation was normal.

Influence of an abnormal ankle-brachial index on ischemic and bleeding events in patients undergoing percutaneous coronary intervention.

BACKGROUND/AIMS: Bleeding events after percutaneous coronary intervention (PCI) have important prognostic implications. Data on the influence of an abnormal ankle-brachial index (ABI) on both ischemic and bleeding events in patients undergoing PCI are limited. METHODS: We included patients who underwent PCI with available ABI data (abnormal ABI, ≤ 0.9 or > 1.4). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), stroke, and major bleeding. RESULTS: Among 4,747 patients, an abnormal ABI was observed in 610 patients (12.9%). During follow-up (median, 31 months), the 5-year cumulative incidence of adverse clinical events was higher in the abnormal ABI group than in the normal ABI group: primary endpoint (36.0% vs. 14.5%, log-rank test, p < 0.001); all-cause death (19.4% vs. 5.1%, log-rank test, p < 0.001); MI (6.3% vs. 4.1%, log-rank test, p = 0.013); stroke (6.2% vs. 2.7%, log-rank test, p = 0.001); and major bleeding (8.9% vs. 3.7%, log-rank test, p < 0.001). An abnormal ABI was an independent risk factor for all-cause death (hazard ratio [HR], 3.05; p < 0.001), stroke (HR, 1.79; p = 0.042), and major bleeding (HR, 1.61; p = 0.034). CONCLUSION: An abnormal ABI is a risk factor for both ischemic and bleeding events after PCI. Our study findings may be helpful in determining the optimal method for secondary prevention after PCI.

Prolonged dual antiplatelet therapy for Chinese ACS patients undergoing emergency PCI with drug-eluting stents: Benefits and risks.

Background: In patients with acute coronary syndrome (ACS), prolonged dual antiplatelet therapy (DAPT) may reduce ischemic events and increase the risks of bleeding events differently in different ethnic groups. However, whether prolonged DAPT in Chinese patients with ACS following emergency percutaneous coronary intervention (PCI) with drug-eluting stents (DES) will be beneficial or dangerous remains unclear. This study aimed to examine the potential benefits and risks of prolonged DAPT in Chinese patients with ACS who have undergone emergency PCI with DES. Methods: This study included 2,249 patients with ACS who underwent emergency PCI. If DAPT was continued for 12 or 12-24 months, it was classified as the standard (n = 1,011) or prolonged (n = 1,238) DAPT group, respectively. The incidence of the following endpoint events was determined and compared between the two groups: composite bleeding event (BARC 1 or 2 types of bleeding and BARC 3 or 5 types of bleeding) and major adverse cardiovascular and cerebrovascular events (MACCEs) [ischemia-driven revascularization, non-fatal ischemia stroke, non-fatal myocardial infarction (MI), cardiac death, and all-cause death]. Results: After a median period of 47 months of follow-up [47 (40, 54)], the rate of composite bleeding events was 13.2% (n = 163) in the prolonged DAPT group and 7.9% (n = 80) in the standard DAPT group [odds ratio (OR) 1.765, 95% confidence interval (CI) 1.332-2.338, p < 0.001]. The rate of MACCEs was 11.1% (n = 138) in the prolonged DAPT group and 13.2% (n = 133) in the standard DAPT group (OR 0.828, 95% CI 0.642-1.068, p = 0.146). The DAPT duration was further shown to be insignificantly correlated with MACCEs as per the multivariable Cox regression model (HR, 0.813; 95% CI, 0.638-1.036; p = 0.094). No statistically significant difference was observed between the two groups. However, the DAPT duration was a separate predictor of composite bleeding events according to the multivariable Cox regression model (HR 1.704, 95% CI 1.302-2.232, p < 0.001). Compared with the standard DAPT group, the prolonged DAPT group had substantially more BARC 3 or 5 types of bleeding events (3.0 vs. 0.9% in those with standard DAPT, OR 3.430, 95% CI 1.648-7.141, p < 0.001) and BARC 1 or 2 types of bleeding events (10.2 vs. 7.0% in those with standard DAPT, OR 1.500, 95% CI 1.107-2.032, p = 0.008). Conclusion: The prolonged DAPT group had a considerably greater incidence of composite bleeding events than the standard DAPT group. No statistically significant difference was observed in the incidence of MACCEs between the two groups.

Endothelial dysfunction predicts bleeding and cardiovascular death in acute coronary syndrome.

BACKGROUNDS: Recently, there has been increasing awareness that bleeding may lead to adverse outcomes. Endothelial dysfunction is associated with increased risk of cardiovascular and bleeding events. This study aimed to investigate the association of endothelial dysfunction with major bleeding and specific causes of death in addition to major adverse cardiovascular events in patients with acute coronary syndrome. METHODS: This single-centre retrospective observational study was conducted at a tertiary-care hospital; patients with acute coronary syndrome were included between June 2010 and November 2014 (median follow-up, 6.1 years). The reactive hyperaemia index was assessed before their discharge; reactive hyperaemia index <1.67 was defined as endothelial dysfunction. The main outcomes were the incidence of major bleeding, all-cause death, cardiovascular death, non-cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. RESULTS: Among the included 674 patients with acute coronary syndrome, 264 (39.2%) had endothelial dysfunction. Multivariable Cox-hazard analyses revealed an independent predictive value of endothelial dysfunction for major bleeding (hazard ratio 2.29, 95% confidence interval 1.17-4.48, P = 0.016) and major adverse cardiovascular events (hazard ratio 2.04, 95% confidence interval 1.43-2.89, P < 0.001). The endothelial dysfunction group patients had a 2.5-fold greater risk of cardiovascular death; however, no association was found with non-cardiovascular death. CONCLUSION: Endothelial dysfunction assessed using reactive hyperaemia index predicted future major cardiovascular event as well as major bleeding and cardiovascular death in patients with acute coronary syndrome.

Anticoagulation Changes Following Major and Clinically Relevant Nonmajor Bleeding Events in Non-valvular Atrial Fibrillation Patients.

Background: Bleeding events are common complications of oral anticoagulant drugs, including both warfarin and the direct oral anticoagulants (DOACs). Some patients have their anticoagulant changed or discontinued after experiencing a bleeding event, while others continue the same treatment. Differences in anticoagulation management between warfarin- and DOAC-treated patients following a bleeding event are unknown. Methods: Patients with non-valvular atrial fibrillation from six anticoagulation clinics taking warfarin or DOAC therapy who experienced an International Society of Thrombosis and Haemostasis (ISTH)-defined major or clinically relevant non-major (CRNM) bleeding event were identified between 2016 and 2020. The primary outcome was management of the anticoagulant following bleeding (discontinuation, change in drug class, and restarting of same drug class). DOAC- and warfarin-treated patients were propensity matched based on the individual elements of the CHA2DS2-VASc and HAS-BLED scores as well as the severity of the bleeding event. Results: Of the 509 patients on warfarin therapy and 246 on DOAC therapy who experienced a major or CRNM bleeding event, the majority of patients continued anticoagulation therapy. The majority of warfarin (231, 62.6%) and DOAC patients (201, 81.7%) restarted their previous anticoagulation. Conclusion: Following a bleeding event, most patients restarted anticoagulation therapy, most often with the same type of anticoagulant that they previously had been taking.

Hemostasis Disturbances in Continuous-Flow Left Ventricular Assist Device (CF-LVAD) Patients-Rationale and Study Design.

Left ventricular assist devices are a treatment option for end-stage heart failure patients. Despite advancing technologies, bleeding and thromboembolic events strongly decrease the survival and the quality of life of these patients. Little is known about prognostic factors determining these adverse events in this group of patients. Therefore, we plan to investigate 90 consecutive left ventricular assist device (LVAD) patients and study in vitro fibrin clot properties (clot lysis time, clot permeability, fibrin ultrastructure using a scanning electron microscope) and the calibrated automated thrombogram in addition to the von Willebrand factor antigen, fibrinogen, D-dimer, prothrombin time/international normalized ratio (PT/INR), and activated partial thromboplastin time (APTT) to identify prognostic factors of adverse outcomes during the course of therapy. We plan to assess the hemostasis system at four different time points, i.e., before LVAD implantation, 3-4 months after LVAD implantation, 6-12 months after LVAD implantation, and at the end of the study (at 5 years or at the time of the adverse event). Adverse outcomes were defined as bleeding events (bleeding in general or in the following subtypes: severe bleeding, fatal bleeding, gastrointestinal bleeding, intracranial bleeding), thromboembolic events (stroke or transient ischemic attack, pump thrombosis, including thrombosis within the pump or its inflow or outflow conduits, arterial peripheral thromboembolism), and death.

Clinical Characteristics and Long-Term Outcomes of Patients With Differing Haemoglobin Levels Undergoing Semi-Urgent and Elective Percutaneous Coronary Intervention in an Asian Population.

Introduction: This study aimed to investigate the impact of anaemia on long-term clinical outcomes in patients who underwent semi-urgent and elective percutaneous coronary intervention (PCI) in an Asian population. Although the effects of anaemia on outcomes in Asian patients are well studied for acute coronary syndrome, its impact on Asian patients undergoing semi-urgent and elective PCI is unclear. Methods: This was a retrospective cohort study of patients who underwent semi-urgent and elective PCI from January 1, 2014, to December 31, 2015, at a tertiary academic centre. A total of 1,685 patients were included. They were stratified into three groups: normal (≥12 g/dL), intermediate (10-11.9 g/dL), and low (<10 g/dL) haemoglobin levels. Demographics, risk factors, and end-points including the 5-point major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, subsequent stroke, myocardial infarction, congestive cardiac failure, and target lesion revascularisation), cardiovascular death, and bleeding events were analysed. Results: Patients in intermediate and low haemoglobin level groups were older with more comorbidities. Compared to the normal haemoglobin level group, low haemoglobin level group patients were associated with an increased risk of composite endpoints of all-cause death, subsequent stroke, myocardial infarction, congestive cardiac failure, and target lesion revascularisation [adjusted hazard ratio (aHR) 1.89, 95% confidence interval (CI):1.22, 2.92; p = 0.004]. This was driven by the increased risk of target lesions revascularisation observed in the low haemoglobin level group compared to the normal haemoglobin level group (aHR 17.74, 95% CI: 1.74, 180.80; p = 0.015). The patients in the low haemoglobin level group were also associated with a higher risk of bleeding events compared to the normal haemoglobin level group (aHR 7.18, 95% CI: 1.13, 45.40; p = 0.036). Conclusion: In our Asian cohort, patients with anaemia undergoing PCI were associated with a higher comorbid burden. Despite adjustments for comorbidities, these patients had higher mortality and worse cardiovascular outcomes following contemporary PCI.

The impact of kidney function in patients on antithrombotic therapy: a post hoc subgroup analysis focusing on recurrent bleeding events from the AFIRE trial.

BACKGROUND: The success of antithrombotic therapies is assessed based on thrombotic and bleeding events. Simultaneously assessing both kinds of events might be challenging, and recurrent bleeding events are often ignored. We tried to confirm the effects of kidney function on outcome events in patients undergoing antithrombotic therapy. METHODS: As a post hoc subgroup analysis of the Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial, a randomized clinical trial with a median follow-up of 36 months, patients were divided into high and low estimated glomerular filtration rate (eGFR) groups with a cutoff value of 50 mL/min. The cumulative incidence of bleeding and crude incidence of recurrent bleeding per 100 patient-years were calculated. We used the Cox regression model with multiple failure time data for recurrent bleeding events. RESULTS: Among 2092 patients, 1386 (66.3%) showed high eGFR. The cumulative bleeding events per 100 patients at 1 year were 5.4 and 6.2 in the high and low eGFR groups, respectively. The difference continued to increase over time. The hazard ratio for time to the first bleeding event in the high eGFR group was 0.875 (95% confidence interval 0.701-1.090, p = .234) and that for the first composite event was 0.723 (95% confidence interval 0.603-0.867, p < .000). The recurrent bleeding events per 100 person-years were 11.3 and 15.3 in the high and low eGFR groups, respectively, with a rate ratio of 0.738 (95% confidence interval 0.615-0.886, p = .001). During the observation period, the risk of bleeding changed with time. It peaked soon after the study enrollment in both groups. It decreased continuously in the high eGFR group but remained high in the low eGFR group. CONCLUSIONS: We reaffirmed that kidney function affects bleeding events in patients on antithrombotic therapy, considering recurrent events. Patients should have detailed discussions with physicians regarding the possible bleeding events when continuing antithrombotic therapy, especially in patients with decreased kidney function. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000016612 . ClinicalTrials.gov, NCT02642419 . Registered on 21 October 2015.

Aspirin Thromboprophylaxis Is Associated With Less Major Bleeding Events Following Total Joint Arthroplasty.

BACKGROUND: There is ongoing debate on what is optimal prophylactic agent to reduce venous thromboembolism (VTE) following total joint arthroplasty (TJA). Although many studies assess the efficacy of these agents in VTE prevention, no attention is given to their adverse effect on major bleeding events (MBEs). This study compared the incidence of MBE in patients receiving aspirin as VTE prophylaxis vs other chemoprophylaxis. METHODS: A single-institution, retrospective study of 35,860 patients undergoing TJA between 2009 and 2020 was conducted. Demographic variables, co-morbidities, type of chemoprophylaxis, and intraoperative factors were collected. MBE was defined using the 2010 criteria for major bleeding in surgical patients presented by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. To enhance capture rate, comprehensive queries utilizing MBE keywords were conducted in clinical notes, physician dictations, and phone call logs. Univariate followed by multivariate regression was performed as well as propensity score matched analysis. RESULTS: Overall, 270 patients (0.75%) in this cohort developed MBE. The MBE rate was 0.5% in the aspirin group and 1.2% in the non-aspirin group. After adjusting for confounders, multiple logistic regression and propensity score matched analysis revealed almost 2 times lower odds of MBE in patients who received aspirin. Variables independently associated with increased MBE risk included increasing age, body mass index, American Society of Anesthesiologists score, revision surgery, peptic ulcer disease, coagulopathy, intraoperative blood transfusion, and active smoking. CONCLUSION: Administration of aspirin for VTE prophylaxis, compared to other chemoprophylaxis agents may have an association with lower risk of major bleeding following TJA. Future randomized controlled trials should examine these findings.

Characteristics and clinical outcomes of patients with de-escalation from prasugrel to clopidogrel after acute myocardial infarction - Insights from the prospective Japan Acute Myocardial Infarction Registry (JAMIR).

BACKGROUND: De-escalation of P2Y12 inhibitor may occur for various clinical reasons in patients with acute myocardial infarction (AMI). We aimed to assess the characteristics and outcomes of patients who underwent a de-escalation strategy in real-world clinical practice. METHODS AND RESULTS: We studied 2604 AMI patients initially treated with prasugrel using the Japan Acute Myocardial Infarction Registry (JAMIR) database. Of these, 110 (4%) were discharged on clopidogrel [de-escalation group; switching 4 days after admission (median)] and the remaining 2494 continued prasugrel at discharge (continuation group). The de-escalation group had higher incidence of heart failure or history of cerebrovascular disease, and were more likely to receive mechanical circulatory support, and oral anticoagulation than the continuation group. During mean follow-up of 309±133 days post-discharge, no significant differences were observed in ischemic events (2.2% vs. 2.8%, p = 0.74) or major bleeding (1.1% vs. 1.6%, p = 0.72) between the de-escalation and continuation groups. CONCLUSIONS: Although, patients with de-escalation from prasugrel to clopidogrel had higher bleeding risk profile than those continued on prasugrel, post discharge ischemic and bleeding events were similar between patients with and without de-escalation. De-escalation strategy may be an option for AMI patients with high risk for bleeding.