Higher Risk Of Bleeding Events Research Articles

Abstract 4135327: Long-term Bleeding Events after Percutaneous Coronary Intervention in Patients with Malignancy with and without Anticoagulant Therapy

Background: With the aging population, the prevalence of malignancies in patients undergoing percutaneous coronary intervention (PCI) is increasing. Active malignancy is increasingly recognized as a significant contributor to high bleeding risks. In cases where anticoagulant (AC) therapy is required, it becomes crucial to determine which is the optimal choice for cancer patients, direct oral anticoagulants (DOACs) or warfarin. The aim of this study was to investigate long-term bleeding events in patients with malignancy undergoing PCI. Methods: CLIDAS (Clinical Deep Data Accumulation System) is a multicenter database with 7 tertiary medical hospitals in Japan. This retrospective analysis using CLIDAS database included 6838 patients who underwent PCI during April 2014 and March 2020 and also who have completed 3-year follow-up were divided into two groups; No malignancy group (n=6155) and malignancy group (n=683). Malignancy was defined as patients with treatment history of malignancy. Furthermore, these patients were categorized into six groups based on the presence of malignancy and the type of AC therapy; 1) No malignancy without AC (n=5369), 2) No malignancy with DOAC (n=294), 3) No malignancy with warfarin (n=492), 4) Malignancy without AC (n=586), 5) Malignancy with DOAC (n=44), and 6) Malignancy with warfarin (n=53). The primary outcome was the incidence of bleeding events, defined according to the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries classification of moderate and severe bleeding. Results: During the 3-year follow-up period, 260 (3.8%) patients experienced major bleeding events after PCI. Among these patients, 180 (3.4%) were in group 1, 9 (3.1%) in group 2, 33 (6.7%) in group 3, 27 (4.6%) in group 4, 2 (4.5%) in group 5, and 9 (17.0%) in group 6. Multivariate Cox regression analysis showed that patients in the malignancy group had a significantly higher rate of bleeding events (HR, 1.50; 95% CI, 1.03-2.18). Furthermore, only the malignancy with warfarin group showed a significantly higher rate of bleeding events compared to the no malignancy without AC group (HR, 4.03; 95% CI, 1.94-8.37). Conclusions: Patients with malignancies receiving warfarin were associated with a higher risk of bleeding events. DOACs may be a safer alternative to warfarin in reducing bleeding risk in this population.

Novel morphological classification of left atrial appendage using 3-dimensional printer -rock, paper and scissors-

Abstract Background The WATCHMAN device was developed as a permanent implantable device to seal off the LAA to prevent cardiogenic embolism. It has been used in Japan since September 2019 only for patients who are at the high risk of bleeding events. It is known that the LAA diameter of Asians is larger than that of non-Asians. Furthermore, the LAA of the Japanese are more complicated, compared to the Western. Whereas the four classifications from previous reports are widely used in the world, the classification differs with different physicians in the real-world practice. Purpose We aimed to identify the relationship between morphological features of LAA and clinical events such as ischemic stroke in Japanese patients. Methods All LAAC cases in our institution performed between February 2020 and December 2023 were retrospectively analyzed. The three-dimensional printing of LAA was generated from cardiovascular computed tomography imaging data. The shapes of the LAA were classified into 3 morphological types: (1) The LAA with bi lobe was defined as "Scissors" type; (2) The one with complicated peripheral branches was "Paper" type; (3) The simple one was "Rock" type. We examined the between the risk of cardioembolic stroke and the morphological features of the LAA. The left atrial appendage was classified by two cardiologists, and when they made different choices, we used the operator's choice. Results The cohort consisted of 116 patients, excluding 22 patients without CT scans. Of those, 30 (26%), 38 (33%) and 48 (41%) patients were divided into the Rock, Scissors and Paper types, respectively. All groups were identically matched for comorbidities. Table shows the patient characteristics and the results of univariate and multivariate analysis. There were 51 (44%) patients who had a history of cardioembolic stroke (18% vs. 30% vs. 53%; Rock vs. Scissors vs. Paper types, p-value = 0.05). In the multivariate analysis, the Paper type is the potential risk factor of cardioembolic stroke (p-value = 0.01). In addition, of those, 36 (31%), 32 (28%), 28 (24%) and 20 (17%) patients were divided into the Chicken wing, Cactus, Cauliflower and Windsock types, respectively. The four types were not associated with prior cardioembolic stroke events (18% vs. 25% vs. 55%; Chicken wing vs. Cactus vs. Cauliflower vs. Windsock types, p-value = 0.83). The match rate of cardiologists’ choice was 86.2% for the new classification and 44.8% for the classical classification. Conclusions The morphological features of LAA by three-dimensional printing was significantly related to cardioembolic stroke in this population. Patients with Paper type LAA were significantly more likely to have had a history of cardioembolic stroke. These results could have a relevant impact on the antithrombotic management of patients who are at the high risk of embolic and bleeding events and, moreover, LAAC could be the best option for these patients.

Sex differences in outcomes of percutaneous left atrial appendage closure

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia in adults and is associated with an increased risk of embolic stroke. In a previous survey, 91% of nonrheumatic AF-related left atrial thrombi was originated in the left atrial appendage (LAA). Percutaneous left atrial appendage closure (LAAC) with the Watchman device has been shown to be noninferior to anticoagulation therapy in clinical trials for stroke prevention in nonrheumatic AF. It has been used in Japan since September 2019 only for patients who are at the high risk of bleeding events. The WATCHMAN family is the only left atrial appendage closure (LAAC) device in Japan. Since long time ago, sex differences have been attracting attention in the cardiology. Due to the cardiovascular protective effects of endogenous estrogens, premenopausal women are thought to be less likely to develop cardiovascular disease. Whereas, in area of AF, Female with AF have higher stroke risk and female with AF have severe after effect. However, there are few studies on sex differences in LAAC implantation outcomes. Purpose We aimed to identify the sex differences of outcomes of LAAC in Japanese patients. Methods A total of 118 consecutive patients who underwent LAAC at our hospital from January 2020 to August 2023 were prospectively analyzed. Various patient characteristics, comorbidities, and outcomes were identified and compared between male and female. Results Results are shown in Table. Female were older (79 vs. 73 years, p = 0.0009), thinner (Body mass index 22 vs. 24 kg/m2, p = 0.0326), and less likely to have had diabetes (19 vs. 40%, p = 0.0340). Pulmonary embolism was significantly more common in female after LAAC. If anticoagulants are discontinued after LAAC, women’s susceptibility to coagulation may become apparent. Conclusions LAAC was feasible and safe for Japanese patients of both genders. However, these results could have a relevant impact on the antithrombotic management of patients who are at the high risk of embolic considering sex difference. Especially, we should pay great attention when discontinuing anticoagulants after LAAC in female.

Catheter ablation alone versus catheter ablation with combined percutaneous left atrial appendage closure for atrial fibrillation: a systematic review and meta-analysis.

Combined catheter ablation (CA) with percutaneous left atrial appendage closure (LAAC) may produce comprehensive treatment for atrial fibrillation (AF) whereby rhythm control is achieved and stroke risk is reduced without the need for chronic oral anticoagulation. However, the efficacy and safety of this strategy is still controversial. This meta-analysis was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Medline, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. The risk of bias was assessed using the Modified Newcastle-Ottawa scale and Cochrane risk of bias tool. Eligible studies reported outcomes in patients with AF who underwent combined CA and LAAC vs CA alone. Studies performing CA without pulmonary vein isolation were excluded. Eight studies comprising 1878 patients were included (2 RCT, 6 observational). When comparing combined CA and LAAC vs CA alone, pooled results showed no difference in arrhythmia recurrence (risk ratio (RR) 1.04; 95% confidence interval (CI) 0.82-1.33), stroke or systemic embolism (RR 0.78; 95% CI 0.27-2.22), or major periprocedural complications (RR 1.28; 95% CI 0.28-5.89). Total procedure time was shorter with CA alone (mean difference 48.45 min; 95% CI 23.06-74.62). Combined CA with LAAC for AF is associated with similar rates of arrhythmia-free survival, stroke, and major periprocedural complications when compared to CA alone. A combined strategy may be as safe and efficacious for patients at moderate to high risk for bleeding events to negate the need for chronic oral anticoagulation.

Natural history of spontaneous pancreatic portal vein fistulae: A systematic review of the literature

BackgroundSpontaneous pancreatic portal vein fistula (PPVF) - a rare complication of pancreatic inflammation – varies widely in presentation and means of diagnosis but has been previously associated with bleeding complications and mortality. A systematic review of published literature was performed to assess the frequency of outcomes. MethodsA search of electronic databases (PubMed, Ovid MEDLINE, Scopus, EMBASE, gray literature) resulted in 1667 relevant unique manuscripts; 52 met inclusion criteria. ResultsA total of 74 unique (male n = 47, 63.5 %) patients were included. Mean age was 53.5 (±11.9) years. History of alcohol use was reported in 55 (74.3 %). Underlying chronic pancreatitis (CP) was present in 49 (66.2 %). In cases where presenting symptoms were reported (n = 57, 77.4 %), the most frequent were abdominal pain (63.5 %), weight loss (14.9 %), rash (12.2 %), nausea/vomiting (12.2 %), and polyarthritis (9.5 %). Computed tomography was the most common imaging modality used to confirm the diagnosis (n = 20, 27.0 %), followed by magnetic resonance cholangiopancreatography (n = 14, 18.9 %). Portal vein thrombosis was reported in 57 (77.0 %), and bleeding events (luminal, variceal, or intra-pseudocyst) were reported in 13(17.6 %) patients. Younger age was associated with higher risk of bleeding events. Mortality was reported in 12 (16.2 %) patients at any time during follow up. Older age and polyarthritis at presentation were associated with mortality. ConclusionsPPVF is a rare and potentially fatal condition, though rates of bleeding complication and death were relatively low in this population. High-quality observational studies are needed to better understand the pathophysiology and natural history of this diagnosis.

Low Remnant Cholesterol and In-Hospital Bleeding Risk After Ischemic Stroke or Transient Ischemic Attack.

Bleeding risk brought by intensive lipid-lowering therapy and low low-density lipoprotein cholesterol is concerning, while evidence regarding the relationship between remnant cholesterol and bleeding is frightening. This study aimed to investigate the association between remnant cholesterol at admission and an in-hospital bleeding event after acute ischemic stroke or transient ischemic attack (TIA). A total of 3222 eligible patients admitted to Shanghai Huashan Hospital between 2015 and 2021 with complete lipid data were analyzed. Patients were classified into low (<20.0 mg/dL), moderate (20.0-29.9 mg/dL), and high (≥30 mg/dL) groups by remnant cholesterol. The mean age of patients was 63.0± 13.1 years, including 2301 (71.4%) men and 651 (20.2%) with TIA. The median (interquartile range) of remnant cholesterol was 18.6 (13.5-25.9) mg/dL. After adjustment for confounding variables, patients with low remnant cholesterol had a higher risk of bleeding events (odds ratio, 2.56 [95% CI, 1.12-6.67]) than those with moderate remnant cholesterol. The high remnant cholesterol group was not significantly associated with bleeding risk. Combined assessment of low-density lipoprotein cholesterol and remnant cholesterol further identified patients with the highest risk of bleeding events. Low remnant cholesterol levels were associated with bleeding events during the acute stage of ischemic stroke and TIA. The assessment of remnant cholesterol could inform the bleeding risk during hospitalization both for patients and physicians in clinical practice.

Three-dimensional printer guided new morphological classification of left atrial appendage -rock, paper and scissors-

Abstract Background Cardiogenic embolism by left atrial thrombi is one of the most important atrial fibrillation (AF)-related clinical problems. In a previous survey, 91% of nonrheumatic AF-related left atrial thrombi was originated in the left atrial appendage (LAA). The WATCHMAN device was developed as a permanent implantable device to seal off the LAA to prevent cardiogenic embolism. It has been used in Japan since September 2019 only for patients who are at the high risk of bleeding events. The WATCHMAN family is the only left atrial appendage closure (LAAC) device in JAPAN. It is known that the LAA diameter of Asians is larger than that of non-Asians. Furthermore, the LAA of the Japanese are more complicated, compared to the Western. Whereas the four classifications from previous reports are widely used in the world, the classification differs with different physicians in the real-world practice. Purpose We aimed to identify the relationship between morphological features of LAA and clinical events such as ischemic stroke in Japanese patients. Methods The LAAC database of our institution was respectively analyzed. All LAAC cases were performed between February 2020 and February 2022. The three-dimensional printing of LAA was generated from cardiovascular computed tomography imaging data. The shapes of the LAA were classified into 3 morphological types: (1) The LAA with bi lobe was defined as "Scissors" type; (2) The one with complicated erasing branches was "Paper" type; (3) The simple one was "Rock" type. We retrospectively examined the relationship between the risk of ischemic stroke and the morphological features of the LAA. Results The cohort consisted of 63 consecutive patients (age, 73±8 years; male gender, 73%; BMI, 24±4 kg/m²; the size of WATCHMAN device, 29±42 mm). Of those, 14 (22%), 21 (33%) and 28 (44%) patients were divided into the Scissors, Paper and Rock types, respectively. All groups were identically matched for comorbidities. Table shows the patient characteristics and the results of univariate and multivariate analysis. There were 35 (56%) patients who had a history of ischemic stroke (4 vs. 9 vs. 22; Rock vs. Scissors vs. Paper types, p-value=0.01). In the multivariate analysis, the Paper type is the potential risk factor of ischemic stroke (p-value&amp;lt;0.01, respectively). Conclusions The morphological features of LAA by three-dimensional printing may be related to cardioembolic stroke. Patients with Paper type LAA were significantly more likely to have had a history of ischemic stroke. These results could have a relevant impact on the antithrombotic management of patients who are at the high risk of embolic and bleeding events and, moreover, LAAC could be the best option for these patients.Table 1Table 2

Abstract 136: Antiplatelet Regimens for Secondary Prevention in Minor Ischemic Stroke or TIA: A Network Meta‐Analysis

Introduction There is increased risk of major cardiovascular events among patients with minor ischemic stroke or transient ischemic attack (TIA) [1]. Antiplatelet drugs have been proven to reduce the risk of major cardiovascular events and highly recommended for secondary stroke prevention in this population [2]. However, using antiplatelets has shown an increase in the risk of bleeding events. Hence there are multiple antiplatelet regimens, we aim to investigate the efficacy and safety of these different regimens in minor ischemic stroke defined as National Institutes of Health Stroke Scale (NIHSS) score of 5 or less and high‐ risk TIA). Methods A comprehensive literature search of (PubMed, Cochrane, Scopus, and WOS) was conducted to identify randomized controlled trials comparing different antiplatelet regimens in patients with minor ischemic stroke or TIA. Frequentist NMA was conducted to estimate relative risks (RR) and 95% confidence intervals (CI) for the outcomes of interest using R statistical programming language [3]. The primary outcome measure was recurrent stroke while secondary outcomes included, any bleeding events, serious adverse events (SAEs), hemorrhagic stroke, myocardial infarction (MI), cardiovascular mortality, and all‐cause mortality. Results Five RCTs with 34,941 participants were included. Compared to SAPT (aspirin alone), both DAPT regimens (aspirin + clopidogrel and aspirin + ticagrelor) demonstrated a significant reduction in stroke recurrence (RR: 0.72 with 95% CI [0.63, 0.82], P &lt; 0.01) and (RR: 0.75 with 95% CI [0.64, 0.87], P &lt; 0.01), respectively. However, both DAPT regimens were associated with a higher risk of bleeding events (RR: 1.95 with 95% CI [1.09, 3.50], P = 0.02), (RR: 3.07 with 95% CI [1.16, 8.15], P = 0.02), respectively. In contrast, no significant differences were observed among various antiplatelet modalities regarding all‐cause mortality, cardiovascular mortality, hemorrhagic stroke, myocardial infarction, and serious adverse events. In contrast, no significant differences were observed among various antiplatelet modalities regarding all‐cause mortality, cardiovascular mortality, hemorrhagic stroke, myocardial infarction, and serious adverse events. Conclusion Our findings indicate that DAPT regimens were effective in reducing stroke recurrence compared to SAPT. However, caution is warranted as both DAPT regimens were associated with a higher risk of bleeding events. Clinicians should weigh the potential benefits of reduced stroke recurrence with DAPT against the increased risk of bleeding events. Further research and clinical trials assessing both safety and efficacy are warranted to better understand the optimal prevention approach for this specific patient population.

Low-molecular-weight heparin in thrombophilic women receiving in vitro fertilization/intracytoplasmic sperm injection: A meta-analysis.

This meta-analysis aimed to evaluate the efficacy and safety of low-molecular-weight heparin (LMWH) on pregnancy outcomes in thrombophilic women receiving in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). A systematic literature search of PubMed, EMBASE, the Cochrane Library, and China National Knowledge Infrastructure was performed to identify randomized controlled trials (RCTs) comparing LMWH with no treatment or placebo published from database inception until February 19, 2023. Primary outcomes were the clinical pregnancy rate and implantation rate, and secondary outcomes were the live birth rate, miscarriage rate, and the risk of bleeding events. The certainty of the evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. Meta-analysis was conducted using STATA 14.0. Five RCTs involving 1094 thrombophilic women receiving IVF/ICSI were finally included. Administration of LMWH was associated with statistically higher clinical pregnancy rate (4 RCTs, risk ratio [RR] 1.50, 95% confidence interval [CI] 1.23-1.82, p < 0.001, low certainty evidence), implantation rate (5 RCTs, RR 1.49, 95% CI 1.25-1.78, p < 0.001, very low certainty evidence), and live birth rate (2 RCTs, RR 2.15, 95% CI 1.60-2.89, p < 0.001, very low certainty evidence), but with statistically lower miscarriage rate (2 RCTs, RR 0.36, 95% CI 0.15-0.86, p = 0.021, very low certainty evidence). However, using LMWH was linked to a higher risk of bleeding events (2 RCTs, RR 2.36, 95% CI 1.49-3.74, p < 0.001, very low certainty evidence). Very low certainty evidence suggests that administration of LMWH may benefit pregnancy outcomes in thrombophilic women receiving IVF/ICSI treatment, although it may also increase the risk of bleeding events. However, before putting our findings into practice, healthcare professionals should conduct an in-depth evaluation of the available evidence and specific patient situations. Furthermore, due to the low methodological quality of the included studies, more high-quality studies are needed to validate our findings in the future.

A novel de-escalation antiplatelet therapy for patients with acute coronary syndrome undergoing percutaneous coronary intervention.

To investigate the effect of different DAPTs in patients with ACS undergoing PCI, and to identify the most efficient DAPT to reduce the risk of ischemia and bleeding after PCI. Between March 2017 and December 2021, 1598 patients with ACS who underwent PCI were included in the study. The DAPT protocol included the clopidogrel group (aspirin 100 mg + clopidogrel 75 mg), ticagrelor group (aspirin 100 mg + ticagrelor 90 mg), de-escalation Group 1 (reduced dose of ticagrelor [from 90 mg to 60 mg]) after 3 months of oral DAPT [aspirin 100 mg + ticagrelor 90 mg]), and de-escalation Group 2 (switched from ticagrelor to clopidogrel after 3 months of oral DAPT [aspirin 100 mg + ticagrelor 90 mg]). All patients received a 12-month follow-up. The primary endpoint was net adverse clinical events (NACEs) that included the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, stroke, and bleeding events. There were 2 secondary endpoints, major adverse cardiovascular and cerebrovascular events (MACCEs) and bleeding. No statistically significant difference was found in the incidence of NACEs between the 4 groups at the average 12-month follow-up (15.7% vs 19.2% vs 16.7% vs 20.4%). Cox regression analysis revealed that DAPT ticagrelor group regimen (hazard ratio [HR] 0.547; 95% confidence interval [CI]: 0.334-0.896; P = .017) were associated with a lower risk of MACCEs. Age (HR 1.024; 95% CI: 1.003-1.046; P = .022). DAPT de-escalation Group 2 regimen (HR 1.665; 95% CI: 1.001-2.767; P = .049) were marginally associated with a higher risk of MACCEs. Ticagrelor group regimen (HR 1.856; 95% CI: 1.376-2.504; P < .001) was associated with higher risk of bleeding events. Ticagrelor group regimen (HR 1.606; 95% CI: 1.179-2.187; P = .003) were associated with a higher risk of minor bleeding events. For patients with ACS underwent PCI, there were no significant difference in the incidence of NACEs between 3 and 12 months after PCI between de-escalation and non-de-escalation therapies. Compared with ticagrelor-based 12-month DAPT, there was no significant difference in MACCEs and bleeding events in patients receiving de-escalation treatment (ticagrelor reduction from 90 to 60 mg, 3 months after PCI).

#3207 KIDNEY FUNCTION ESTIMATORS FOR DRUG DOSE ADJUSTMENT OF DIRECT ORAL ANTICOAGULANTS IN OLDER ADULTS WITH ATRIAL FIBRILLATION

Abstract Background and Aims The Food and Drug Administration and the European Medicines Agency (EMA) recommend using the Cockcroft-Gault equation (CG) for drug dose adjustment of direct oral anticoagulant drugs (DOACs) in non-valvular atrial fibrillation (NVAF), whereas Cardiology guidelines recommend using estimated glomerular filtration rate (eGFR). This issue is of great importance in older adults, which are more prone to adverse drug reactions and have higher prevalence of atrial fibrillation as compared to younger adults, and in whom CG has worse diagnostic performance than most eGFR equations. We aimed to assess if prognosis was similar according to drug dose status using different kidney function estimators based on creatinine and/or cystatin C in older adults with NVAF. Method We used data from the Berlin Initiative Study (BIS): a population-based prospective cohort study initiated in 2009, with five biennial study visits. Participants with a history of NVAF (based on ICD-10 codes) and a dispensed prescription of DOAC four months prior to baseline or a follow-up visit according to claims data were included. Drug dose status was defined according to the EMA guidelines. CG, deindexed (in ml/min) creatinine and/or cystatin C-based CKD-EPI, and deindexed BIS 1 (creatinine-based) and BIS 2 (creatinine and cystatin C-based) equations were included. Associations between dosing status and mortality, stroke or systemic embolism, and bleeding events were assessed using marginal structural Cox models with time-varying variables and taking account of various confounders. Subgroup analyses were performed in rivaroxaban and apixaban users, but not in dabigatran and edoxaban users because of too small sample sizes. Results Two hundred twenty four patients treated with DOACs were included in this analysis (median age 87 years, median eGFRCKD-EPIcr 56 ml/min/1.73m², median follow-up length 40 months for the mortality analysis). Of those, 99 (44%) were taking rivaroxaban, 86 (38%) apixaban, 21 (9%) edoxaban, and 18 (8%) dabigatran. Using CG, 154 (69%) had appropriate DOAC dose at baseline, 52 (23%) were underdosed, and 18 (8%) were overdosed. Discrepancies were found by comparing dosing status according to CG and eGFR equations (Figure 1). During the follow-up period, 109 (14.9/100 person-years) participants died, 25 (3.6/100 person-years) experienced a stroke or systemic embolism, and 60 (9.9/100 person-years) experienced a bleeding event. Drug dose status was not significantly associated with mortality and the occurrence of stroke or systemic embolism, whatever equation was used. Underdose status was associated with a significantly lower risk of bleeding events with all the equations but overdose status was not associated with a higher risk of bleeding events (Figure 2). In subgroup analyses, drug dose status was not associated with mortality and bleeding event in apixaban users, whatever equation was used. In rivaroxaban users, underdose status was associated with a significant higher risk of death by using CG, eGFRCKD-EPIcys, and BIS 2, and a lower risk of bleeding event by using eGFRCKD-EPIcr. Conclusion In this population of very old adults with NVAF, drug dose status of DOAC was not associated with mortality or the occurrence of stroke or systemic embolism for any of the studied equations. However, underdose status was associated with bleeding events occurrence regardless of the equation used. These associations differed according to the used drug, but this should be interpreted with cautious due to small sample sizes. Our results do not allow us to provide any guidance which equation to use in this context. A study including a larger group of patients with discrepancy in dose status according to the used equations would be of great interest.

Clinical Outcomes Based on High Bleeding Risk in Patients With Lower Extremity Peripheral Artery Disease Who Have Undergone Endovascular Therapy.

Endovascular therapies (EVTs) for symptomatic lower extremity peripheral artery disease (PAD) are efficient and minimally invasive. However, patients with PAD tend to have high bleeding risk (HBR), and there are limited data regarding the HBR for patients with PAD after EVT. In this study, we investigated the prevalence and severity of HBR, as well as its association with clinical outcomes in the patients with PAD who underwent EVT. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria were applied to 732 consecutive patients with lower extremity PAD post-EVT to assess the prevalence of HBR, and its association with major bleeding events, all-cause mortality, and ischemic events. The ARC-HBR scores (1 point for each major criterion and 0.5 points for each minor criterion) were obtained and the patients were divided into four groups (score: 0-0.5; low risk, score: 1-1.5; moderate risk, score: 2-2.5; high risk, and score: ≥3; very high risk) according to the score. Major bleeding events were defined as Bleeding Academic Research Consortium type-3 or type-5 bleeding, and ischemic events were defined as the composite of myocardial infarction, ischemic stroke, and acute limb ischemia within 2 years. High bleeding risk occurred in 78.8% of the patients. Major bleeding events, all-cause mortality, and ischemic events occurred in 9.7%, 18.7%, and 6.4% of the study cohort, respectively, within 2 years. During the follow-up period, major bleeding events significantly increased with the ARC-HBR score. The severity of the ARC-HBR score was significantly associated with an increased risk of major bleeding events (high risk: adjusted hazard ratio [HR] 5.62; 95% confidence interval [CI]: [1.28, 24.62]; p=0.022; very high risk: adjusted HR: 10.37; 95% CI: [2.32, 46.30]; p=0.002). All-cause mortality and ischemic events also significantly increased with higher ARC-HBR score. High bleeding risk patients with lower extremity PAD can be at a high risk of bleeding events, mortality, and ischemic events after EVT. The ARC-HBR criteria and its associated scores can successfully stratify HBR patients and assess the bleeding risk in patients with lower extremity PAD who undergo EVT. Endovascular therapies (EVTs) for symptomatic lower extremity peripheral artery disease (PAD) are efficient and minimally invasive. However, patients with PAD tend to have high bleeding risk (HBR), and there are limited data regarding the HBR for patients with PAD after EVT. Post EVT, most of the patients with PAD were classified as having HBR using the Academic Research Consortium for HBR (ARC-HBR) criteria and the rate of bleeding events as well as mortality and ischemic events within 2 years increased as the ARC-HBR score increased in this retrospective study of 732 participants. HBR patients with PAD can be at high risk of not only bleeding events but also mortality and ischemic events in the mid-term. The ARC-HBR criteria and its associated scores can successfully stratify HBR patients and assess the bleeding risk in patients with PAD who underwent EVT.

Aspirin use and bleeding events during thrombocytopenia after autologous stem-cell transplantation for multiple myeloma.

In patients with cardiovascular (CV) comorbidities that necessitate antiplatelet therapy (APT), its optimal management during chemotherapy-induced thrombocytopenia remains elusive, as the risk of bleeding has to be balanced against the risk of CV events. The purpose of this study was to assess the risk for bleeding with APT during thrombocytopenia in patients with multiple myeloma undergoing high-dose chemotherapy and subsequent autologous stem-cell transplantation (ASCT) with and without acetylsalicylic acid (ASA) as comedication. We assessed patients who underwent ASCT at the Heidelberg University Hospital between 2011 and 2020 for bleeding events, management strategies for ASA intake during thrombocytopenia, transfusion requirements, and the occurrence of CV events. There were 57/1,113 patients who continued ASA until at least 1 day after ASCT; thus, a continuous platelet inhibition during thrombocytopenia was assumed. Most of the patients (41/57) continued ASA until they had a platelet count of 20-50/nl. This range reflects the kinetics of thrombocytopenia and nondaily measurements of platelets during ASCT. A tendency toward a higher risk for bleeding events in the ASA group was demonstrated (1.9% (control group) vs. 5.3% (ASA), p = 0.082). The risk factors for bleeding in multivariate analysis were the duration of thrombocytopenia < 50/nl, a history of gastrointestinal bleeding, and diarrhea. The factors predicting the duration of thrombocytopenia were age >60 years, a hematopoietic stem-cell transplantation comorbidity index ≥3, and an impaired bone marrow reserve at admission. CV events occurred in three patients; none of them took ASA or had an indication for APT. The intake of ASA until thrombocytopenia with a platelet count of 20-50/nl appears safe, although an elevated risk cannot be excluded. If ASA is indicated for the secondary prevention of CV events, the evaluation of risk factors for bleeding and a prolonged time of thrombocytopenia before conditioning is crucial to adapt the strategy for ASA intake during thrombocytopenia.

Combination of Primary Hemostatic Disorders and Atrial Fibrillation Increases Bleeding Events Following Transcatheter Aortic Valve Replacement.

Background Patients with atrial fibrillation (AF) are likely to have a poor prognosis including bleedings following transcatheter aortic valve replacement (TAVR). Closure time of adenosine diphosphate (CT-ADP) is a primary hemostasis point-of-care test and is a predictor of bleeding events following TAVR. We aimed to evaluate the impact of ongoing primary hemostatic disorders on bleeding events in TAVR patients with AF. Methods We enrolled 878 patients from our prospective registry. The primary endpoint was VARC-2 major/life-threatening bleeding complications (MLBCs) at 1 year after TAVR and secondary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) at 1 year, defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization. Ongoing primary hemostatic disorder was defined by a postprocedural CT-ADP >180 seconds. Results Patients with AF had a higher incidence of MLBCs (20 vs. 12%, p = 0.002), MACCE (29 vs. 20%, p = 0.002), and all-cause mortality (15 vs. 8%, p = 0.002) within 1 year compared to non-AF patients. When the cohort was split into four subgroups according to AF and CT-ADP >180 seconds, patients with AF and CT-ADP >180 seconds had the highest risk of MLBCs and MACCE. Multivariate Cox regression analysis confirmed that the patients with AF and CT-ADP >180 seconds had 3.9-fold higher risk of MLBCs, whereas those patients were no longer associated with MACCE after the adjustment. Conclusion In TAVR patients, AF with postprocedural CT-ADP >180 seconds was strongly associated with MLBCs following TAVR. Our study suggests that persistent primary hemostatic disorders contribute to a higher risk of bleeding events particularly in AF patients.

Ischemic and Bleeding Outcomes in Patients Who Underwent Percutaneous Coronary Intervention With Chronic Kidney Disease or Dialysis (from a Japanese Nationwide Registry)

The relation between chronic kidney disease (CKD) and outcomes in patients receiving percutaneous coronary intervention (PCI) is thought to be bidirectional; these patients are at a higher risk of ischemic and bleeding events. From a Japanese nationwide PCI registry, ischemic (cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke) and bleeding events (fatal or nonfatal major bleeding) 1 year after discharge among patients who had second- or newer-generation drug-eluting stent implantation were analyzed. Patients on oral anticoagulants were excluded. Patients were stratified according to their preprocedural renal function: CKD stages 1 to 2 (estimated glomerular filtration rate [eGFR] ≥60ml/min/1.73m2), 3 (eGFR 30 to 59), or 4 to 5 (eGFR <30), or those receiving dialysis. Overall, 23,349 patients, including 2,798 patients with CKD 3 to 5 (12.0%) and 1,464 patients on dialysis (6.3%), were investigated. One-year ischemic events were observed in 1.5%, 5.2%, 9.7%, and 5.3% in the CKD stages 1-to-2, 3, 4-to-5, and dialysis groups, respectively; patients with CKD stages 3 or 4 to 5 and those receiving dialysis were associated with higher risks of ischemic events after adjustment of covariates than were patients without CKD. Compared with ischemic events, 1-year bleeding events were low, with incidence rates of 1.5%, 2.0%, 3.4%, and 2.3%, respectively. Furthermore, the presence of CKD or dialysis was not associated with a higher risk of bleeding events after adjustment of covariates. In conclusion, in the contemporary nationwide PCI registry, the presence of CKD and dialysis was independently associated with a higher risk of ischemic events but not with bleeding events, and this suggests a need to alter the models of care delivery in these patients.

Mansoor's Self-Report Tool for Cardiovascular Risk Assessment predicts adverse in-hospital events in patients with pulmonary embolism.

Pulmonary embolism (PE) is a life-threatening acute disease accompanied by high morbidity and mortality. Regarding hospitalizations of patients with PE, risk stratification of these patients is crucial. Thus, risk stratification tools like risk scores are of key interest. The nationwide German inpatient sample of the years 2005-2018 was used for this present analysis. Hospitalized PE patients were stratified according to Mansoor's Self-Report Tool for Cardiovascular Risk Assessment class, and the performance of this score was evaluated to predict adverse in-hospital events. Overall, 1 174 196 hospitalizations of PE patients (53.5% females; 56.4% ≥70 years) were registered in Germany between 2005 and 2018. According to the Mansoor's self-report tool for cardiovascular risk assessment, 346 126 (29.5%) PE patients were classified as high risk. Higher Mansoor's Self-Report Tool for Cardiovascular Risk Assessment class was predictive for in-hospital death (OR 1.129 [95%CI 1.117-1.141], P < 0.001), shock (OR 1.117 [95%CI 1.095-1.140], P < 0.001), cardiopulmonary resuscitation (OR 1.109 [95%CI 1.092-1.126], P < 0.001), right ventricular dysfunction (OR 1.039 [95%CI 1.030-1.048], P < 0.001), intracerebral bleeding (OR 1.316 [95%CI 1.275-1.358], P < 0.001), and gastro-intestinal bleeding (OR 1.316 [95%CI 1.275-1.358], P < 0.001). Systemic thrombolysis was not associated with lower in-hospital mortality in high-risk class (OR 5.139 [95%CI 4.961-5.323], P < 0.001). Prognostic performance of the Mansoor's Self-Report Tool for Cardiovascular Risk Assessment for risk stratification of PE patients was poor and not able to identify those PE patients, who might benefit from systemic thrombolysis. However, the Mansoor's Self-Report Tool for Cardiovascular Risk Assessment was moderately helpful to identify PE patients at higher risk for bleeding events.

Risk and benefit trade-off of thromboprophylaxis in patients with Fontan circulation: insights from the National Database of Health Insurance Claims of Japan

Abstract Background Patients with Fontan circulation are at an increased risk of developing thromboembolic events in the first 3–12 months after surgery [1,2]. Thromboembolic events can lead to significant mortality [3]. The current guidelines recommend the use of antithrombotic therapy, either aspirin or warfarin, as a primary thromboprophylaxis [4,5]. On the other hand, the main adverse effect of thromboprophylaxis is bleeding, which may increase the risk of death. However, there are limited data to assess the outcomes of the thromboembolic and bleeding complications of thromboprophylaxis. Therefore, this retrospective cohort study aimed to evaluate the safety and efficacy of thromboprophylaxis after Fontan surgery. Methods We identified 1903 patients who underwent Fontan surgery between June 2011 and September 2019 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. The patients were followed-up from 2 months to 1 year after Fontan surgery to assess the primary outcomes of thromboembolic and bleeding events. Moreover, we identified the factors associated with primary outcomes in this population using multivariate logistic regression analysis. Results A total of 1903 patients (56.1% male) underwent Fontan surgery at a median age of 3 years (1–22); 1815 patients (95.4%) had an extracardiac conduit. No thromboprophylaxis was prescribed to 65 patients (3.4%), whereas 228 patients (12.0%) received aspirin alone, 346 patients (18.2%) received warfarin alone, and 1264 patients (66.4%) received a combination therapy of aspirin and warfarin. In the first post-operative year, thromboembolic events occurred in 234 patients (12.3%) and bleeding events occurred in 202 patients (10.6%). Older age (odds ratio, 1.08; 95% confidence interval, 1.06–1.11) and aspirin use (odds ratio, 0.34; 95% confidence interval, 0.15–0.78) were independently associated with thromboembolic events. In particular, up to 5 months after surgery, the incidence rate of thromboembolism was significantly lower in patients who received aspirin alone (0.9%) than in those who received other thromboprophylaxis regimens (no thromboprophylaxis, 13.8%; warfarin, 7.5%; combination therapy, 7.4%; p&amp;lt;0.05). No significant difference in incidence of bleeding events was observed among the four thromboprophylaxis regimens. A history of postoperative hemorrhage (odds ratio, 1.49; 95% confidence interval, 1.01–2.21) and the use of a potassium channel blocker (odds ratio, 2.12; 95% confidence interval, 1.10–4.05) was associated with a higher risk of bleeding events. Conclusions In this study, patients who received aspirin alone showed a significantly lower incidence of thromboembolic events. Aspirin may be useful for preventing thromboembolism a year after Fontan surgery. After Fontan surgery, it is important to select a safe and effective thromboprophylaxis regimen and evaluate the risk factors for thromboembolic and bleeding events in a timely manner. Funding Acknowledgement Type of funding sources: None.

Does High-Dose Thromboprophylaxis Improve Outcomes in COVID-19 Patients? A Meta-analysis of Comparative Studies.

Background Thromboembolism remains a detrimental complication of novel coronavirus disease (COVID-19) despite the use of prophylactic doses of anticoagulation Objectives This study aimed to compare different thromboprophylaxis strategies in COVID-19 patients Methods We conducted a systematic database search until June 30, 2022. Eligible studies were randomized (RCTs) and nonrandomized studies that compared prophylactic to intermediate or therapeutic doses of anticoagulation in adult patients with COVID-19, admitted to general wards or intensive care unit (ICU). Primary outcomes were mortality, thromboembolism, and bleeding events. Data are analyzed separately in RCTs and non-RCTs and in ICU and non-ICU patients. Results. We identified 682 studies and included 53 eligible studies. Therapeutic anticoagulation showed no mortality benefit over prophylactic anticoagulation in four RCTs (odds ratio [OR] = 0.67, 95% confidence interval [CI], 0.18–2.54). Therapeutic anticoagulation didn't improve mortality in ICU or non-ICU patients. Risk of thromboembolism was significantly lower among non-ICU patients who received enhanced (therapeutic/intermediate) anticoagulation (OR = 0.21, 95% CI, 0.06–0.74). Two additional RCTs (Multiplatform Trial and HEP-COVID), not included in quantitative meta-analysis, analyzed non-ICU patients, and reported a similar benefit with therapeutic-dose anticoagulation. Therapeutic anticoagulation was associated with a significantly higher risk of bleeding events among non-randomized studies (OR = 3.45, 95% CI, 2.32–5.13). Among RCTs, although patients who received therapeutic-dose anticoagulation had higher numbers of bleeding events, these differences were not statistically significant. Studies comparing prophylactic and intermediate-dose anticoagulation showed no differences in primary outcomes. Conclusion There is a lack of mortality benefit with therapeutic-dose over prophylactic-dose anticoagulation in ICU and non-ICU COVID-19 patients. Therapeutic anticoagulation significantly decreased risk of thromboembolism risk in some of the available RCTs, especially among non-ICU patients. This potential benefit, however, may be counter balanced by higher risk of bleeding. Individualized assessment of patient's bleeding risk will ultimately impact the true clinical benefit of anticoagulation in each patient. Finally, we found no mortality or morbidity benefit with intermediate-dose anticoagulation.

Dual Antiplatelet Therapy in Patients Aged 75 Years and Older with Coronary Artery Disease: A Meta-Analysis and Systematic Review.

Objectives This systematic review and meta-analysis evaluates the safety and efficacy of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS). Background The safety and efficacy of DAPT in elderly patients with ACS is not well characterized. Methods We performed a systematic literature review to identify clinical studies that reported safety and efficacy outcomes after DAPT for ACS in elderly patients. The primary outcomes of primary efficacy endpoint rates and bleeding event rates were reported as random effects risk ratio (RR) with 95% confidence interval. No prior ethical approval was required since all data are public. Results Our search yielded 660 potential studies. We included 8 studies reporting on 29,217 patients. There was a higher risk of bleeding event rates in elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 1.17 (95% CI 1.08 to 1.27, p < 0.05). There was no difference in primary efficacy endpoint rates between elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 0.85 (95% CI 0.68 to 1.07, p=0.17). Conclusions This systematic review and meta-analysis suggests that DAPT with prasugrel or ticagrelor compared to clopidogrel is associated with a higher risk of bleeding events in elderly patients with ACS. There was no difference in the primary efficacy endpoints between the two treatment groups.

Dengzhan Shengmai capsule versus Aspirin in the treatment of carotid atherosclerotic plaque: A single-centre, non-inferiority, prospective, randomised controlled trial

BackgroundAspirin is an effective antiplatelet agent for the treatment of carotid atherosclerosis. However, the high risk of bleeding events associated with the drug makes it necessary to seek a safer alternative, with similar or more efficacy than aspirin. Dengzhan Shengmai (DZSM) capsules have been widely used to treat carotid atherosclerosis, and if proven to be non-inferior to aspirin, it may be preferable over the latter for carotid atherosclerosis treatment due to its numerous advantages. We conducted a randomised trial to test the non-inferiority of DZSM to aspirin for the treatment of carotid atherosclerotic plaques. MethodsWe performed a single-centre, prospective, open-label, randomised non-inferiority trial. Patients with carotid atherosclerotic plaques were enrolled and randomly assigned (1:1) to receive either DZSM capsules or aspirin. The follow-up period was 12 months. The primary outcome was the mean change in carotid intima-media thickness (IMT). Secondary outcomes included ischaemic events, rate of lumen stenosis, lipid levels, and plaque scores, length, counts, and vulnerability. Adverse events and laboratory test results were recorded as safety outcomes. The non-inferiority of DZSM was demonstrated when the lower limit of the one-sided 97.5% confidence interval (CI) of the difference in IMT between groups was more than -0.06 mm (margin of non-inferiority). This trial has been registered at ClinicalTrials.gov (CHiCTR1900021365). ResultsFrom 1 April 2019 to 30 September 2019, 150 patients were enrolled, and there was no statistical difference in demographics between the groups. Intention-to-treat analysis showed that the decrease in IMT(∆IMT) was 0.216 ± 0.160 and 0.225 ± 0.149 mm in the DZSM and aspirin groups, respectively. The one-sided 97.5% CI for the difference between ∆IMTs was (-0.0593, +∞). The non-inferiority of DZSM was demonstrated (Pnon-inferiority = 0.0234). There was no significant difference in the incidence of ischaemic events between the groups (P = 1.0). The DZSM group had significantly reduced plaque scores (P < 0.0001), length (P < 0.0001), and counts (P < 0.0001), and improved plaque vulnerability (P < 0.0001). The DZSM group also had reduced levels of low-density lipoprotein cholesterol (LDL-C) (P < 0.0001). Finally, the DZSM group had a lower incidence of total adverse events (14.7% vs. 28%, P = 0.046), especially gastrointestinal discomfort (5.3% vs. 16%, P = 0.034). Although there was no significant difference in bleeding events (0 vs. 5.3%, P = 0.120), the DZSM group tended to have a lower incidence. ConclusionThis trial demonstrated that DZSM was not inferior, in efficacy, to aspirin in treating carotid atherosclerotic plaques, and was found to be superior to aspirin in terms of safety. This study provides a new approach for treating carotid plaques, especially in aspirin-intolerant patients.