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Background: Increasingly research studies use HES (Hospital Episode Statistics) data to report clinical outcomes. No data exists on the performance of individual ICD-10 (International Classification of Diseases 10th Revision) diagnostic codes for identifying major bleeding events. Data from the ROBOT-ACS study provide a unique opportunity to assess this compared to conventionally adjudicated bleeding by standard definitions. Methods: A secondary analysis was performed on the 1172 HES records from ROBOT-ACS follow up data containing bleeding or anaemia codes. The 213 adjudicated major bleeds in ROBOT-ACS served as the gold standard comparator. Individual bleeding codes, and groups by type, were assessed for their positive predictive value (PPV). Results: The PPV of most codes for major bleeding were poor, generally < 50%. The best performing group of codes were relating to intracranial haemorrhage. 26 of 213 adjudicated bleeding events in ROBOT-ACS would be missed if anaemia codes were not considered. Conclusions: The performance of diagnostic ICD-10 codes in HES, without further interrogation, for determining major bleeding events is poor. Whilst sensitivity is likely to be favourable, differentiating major bleeding is challenging. Options for using HES data to determine bleeding in cardiovascular studies would be either a hybrid approach, with HES screening followed by records review, or creating a new definition of significant bleeding using data more readily available in HES. Trial registration: ROBOT-ACS is registered on clinicaltrials.gov. Unique identifier: NCT02484924. Registered 30/6/2015. [ABSTRACT FROM AUTHOR]

Objective: To analyze clinical characteristics of non-anticoagulated subjects with major bleeding, and to determine the incidence of adverse events, healthcare resource utilization (HCRU) and associated costs following a major bleeding event. Methods: Retrospective observational cohort study that analyzed secondary data from electronic health records in Spain. Non-anticoagulated patients with a first major bleeding during the study period (between January 2013 and December 2022) were analyzed for 3 years. Results: A total of 4089 patients (mean age 57.26 (12.87) years, 58.47% female) were included. A proportion of 27.63% presented with genitourinary bleeding, 22.43% with gastrointestinal bleeding, 5.16% with respiratory bleeding and 3.11% with intracranial hemorrhage. At the end of the first major bleeding event, 0.56% of patients died (5.51% after intracranial hemorrhage, 3.23% in case of trauma-related bleeding). The incidence rates of clinical outcomes per 100 person-years within the first 3 months of the major bleeding were death from any cause 7.51 (95% CI 6.70–8.32), cardiovascular death 1.80 (95% CI 1.39–2.21), acute myocardial infarction 4.53 (95% CI 3.89–5.17), and ischemic stroke 3.52 (95% CI 2.96–4.08), and decreased over time. At year 3, mean overall major bleeding cost per patient was EUR 13,310.00 (5153.05), of which EUR 7648.20 (2674.46) (57.46%) accounted for in-hospital costs to treat the major bleeding event. Conclusions: Among non-anticoagulated patients presenting with a first major bleeding, <1% of patients died during index hospitalization. However, these patients had a substantial risk of adverse clinical events during the follow-up, as well as high associated HCRU and costs. [ABSTRACT FROM AUTHOR]

Background: Major bleeding or emergency surgery are the most frequently observed emergency situations in patients anticoagulated with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). The restart of anticoagulation after these situations is a therapeutic dilemma. Methods: The prospective RADOA registry is an observational, noninterventional multicenter registry that documents the management of severe bleeding or emergency surgery in patients treated with VKAs or DOACs. In this substudy, we analyzed time point, type, and dosage of anticoagulant resumption after emergency situations. Results: Overall, 78 emergency surgery patients and 193 major bleeding patients were analyzed. Median age was similar in the VKA- and DOAC-treated groups (emergency surgery: 77 years, major bleeding: 79 years). Anticoagulants were restarted significantly earlier after emergency surgery compared to major bleeding, with no difference between the VKA and DOAC groups. While patients after cardiothoracic surgery received UFH intravenously, patients with trauma or having received abdominal surgery were mainly treated with prophylactic LMWH s.c.. After major bleeding, the majority of patients were treated with prophylactic LMWH. None of the patients in the emergency surgery group and 17% (4/24) of the major bleeding group with recurrent bleeding (12%, 24/193) experienced recurrent bleeding after restart of anticoagulation. Thromboembolism occurred rarely in both patient groups (emergency surgery: 3%, major bleeding 4%). Conclusions: Time points of restart, type, and dosage of anticoagulants are highly diverse in this high-risk patient population. Resumption of prophylactic anticoagulation is associated with a low risk of thrombosis and should be initiated as soon as possible. [ABSTRACT FROM AUTHOR]

Major bleeding is a life-threatening condition with high morbidity and mortality. Trauma, gastrointestinal bleeding, haemoptysis, intracranial haemorrhage or other causes of bleeding represent major concerns in the Emergency Department (ED), especially when complicated by haemodynamic instability. Severity and source of bleeding, comorbidities, and prior use of anticoagulants are pivotal factors affecting both the clinical status and the patients' differential response to haemorrhage. Thus, risk stratification is fundamental in the initial assessment of patients with bleeding. Aggressive resuscitation is the principal step for achieving haemodynamic stabilization of the patient, which will further allow appropriate interventions to be made for the definite control of bleeding. Overall management of major bleeding in the ED should follow a holistic individualized approach which includes haemodynamic stabilization, repletion of volume and blood loss, and reversal of coagulopathy and identification of the source of bleeding. The aim of the present practical guide is to provide an update on recent epidemiological data about the most common etiologies of bleeding and summarize the latest evidence regarding the bundles of care for the management of patients with major bleeding of traumatic or non-traumatic etiology in the ED. [ABSTRACT FROM AUTHOR]

Background: Dose adjustments of direct‐acting oral anticoagulants (DOACs) for atrial fibrillation are based on pivotal clinical trials assessing their effectiveness and safety in controlled settings. However, the appropriateness of these dosing strategies in real‐world practice is uncertain. The purpose of this study is to compare the effectiveness and safety of dose‐specific DOACs with those of warfarin. Methods: This study retrieved articles from MEDLINE, Embase, and CENTRAL until March 5, 2024. Primary outcomes were the incidence of stroke/systemic embolisms (S/SEs) and major bleeding (MB). Direct pairwise meta‐analyses compared each dose‐specific DOAC with warfarin. Heterogeneity was assessed using Higgin's I2 and Q statistics, while publication bias was evaluated through funnel plots and Begg's and Egger's tests, with adjusted pooled estimates calculated via trim‐and‐fill and precision‐effect estimate with standard error (PET‐PEESE) methods. A network analysis was conducted, with additional comparisons made using a Bayesian random‐effects model for indirect evidence. Results: A total of 32 studies with 2,332,770 patients were included. Both standard‐dose (SD) and low‐dose (LD) DOACs significantly reduced S/SE, except for LD apixaban and LD edoxaban. Rivaroxaban did not show significant difference in MB compared to warfarin. In East Asian patients, all doses of DOACs exhibited lower hazard ratios (HRs) for S/SE and MB than those observed in the primary analysis, with LD rivaroxaban significantly reducing MB, a finding not observed in the primary analysis. Rank probability analysis indicated that the dose‐specific DOACs had different safety profiles and small but meaningful differences in effectiveness. SD apixaban (S/SE: second, MB: second) and edoxaban (S/SE: first, MB: fourth) and LD edoxaban (S/SE: fourth, MB: first) had high ranks. LD apixaban had the most significant difference in rank for S/SE from SD apixaban, ranking eighth compared to second. Conclusions: This study found that all DOACs provided comparable or superior effectiveness and safety to warfarin. SD apixaban, SD edoxaban, and LD edoxaban achieved a favorable balance between preventing S/SE and MB risk. [ABSTRACT FROM AUTHOR]

Patients on double antiplatelet treatment who need early in-hospital coronary artery bypass grafting (CABG) are at high risk of major bleeding. In this study, we aimed to investigate the impact of ticagrelor preloading on CABG related bleeding in patients with ST-segment elevation myocardial infarction (STEMI) initially managed with primary percutaneous coronary intervention (pPCI). Patients with the diagnosis of STEMI who were managed with pPCI and underwent subsequent early (4–7 days following pPCI) or delayed (> 7 days following pPCI) on-pump CABG surgery were included. All study patients were preloaded with ticagrelor 180 mg prior to pPCI procedure. Patients' demographics, clinical variables, and short-term cardiovascular outcomes were recorded. This is a retrospective study which included 98 patients. Fifty-four (54%) patients underwent early and 44 (45%) patients underwent delayed CABG surgery. CABG-related bleeding occurred in 22 (22.4%) patients. There was no significant difference with respect to total ticagrelor dose and timing of the surgery between patients with or without CABG-related bleeding (p: 0.165 and p: 0.142). Multivariate analyses demonstrated that only preoperative hemoglobin level < 10.9 and use of mechanical cardiac support devices were independent predictors of CABG-related bleeding [OR: 3719, p: 0.009 and OR: 11,698, p: 0.004, respectively].There were three deaths within the 30 days of surgery, all occurring in patients with CABG-related bleeding. However, CABG-related bleeding was not associated with long-term cardiovascular events during the follow-up. Our results indicated that discontinuation of ticagrelor therapy 3 days prior to surgery is sufficient to avoid CABG-related bleeding. Moreover, early CABG following STEMI does not increase the risk of long-term cardiovascular events. [ABSTRACT FROM AUTHOR]

Patients with atrial fibrillation (AF) commonly have associated comorbidities. The primary aim was to determine the effect of increasing numbers of comorbidity on clinical outcomes. The secondary aims were (1) the association of comorbidities with oral anticoagulants (OAC) discontinuation, and quality control, (2) the impact of holistic care based on the ABC pathway on clinical outcomes. The primary outcome was the composite of all-cause death, ischemic stroke/systemic embolism, major bleeding, and heart failure. A total of 3405 patients were enrolled; mean age 67.8 ± 11.3 years, 41.8% female. Compared to low comorbidity group [n = 897 (26.3%)], hazard ratios (HR) and 95% confidence intervals (CI) for the composite outcome in the high [n = 929 (27.3%)] and moderate comorbidity [n = 1579 (46.4%)] groups were 5.40 (4.20–6.94) and 2.54 (1.97–3.27), respectively. ABC pathway adherence was associated with reduction of the composite outcome overall (HR 0.63; 0.54–0.74). High comorbidity adversely impacted on OAC use, OAC discontinuation, and quality of warfarin control. If quality of anticoagulation control was included as part of the ABC pathway adherence, the reduction in composite outcome risk was greater (HR 0.46; 0.36–0.58). During 3-year follow-up, 33.9% changed from low- to the moderate-high comorbidity groups and 22.3% changed from moderate- to the high comorbidity group. In conclusion, comorbidity burden in AF patients is an important determinant of clinical outcomes, and changed over time. OAC use, OAC discontinuation, and quality of OAC control were impacted by comorbidity burden. ABC pathway adherence was associated with a reduced risk of adverse clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetes mellitus (DM) and atrial Fibrillation (AF) are among the most common health issues. They are responsible for the highest rates of morbidity and mortality. The importance of sodium glucose cotransporter-2 inhibitors (SGLT-2is) in treating DM has increased significantly in recent years. In our article, we aimed to evaluate the effect of SGLT-2i on the clinical outcomes of AF patients with DM. Methods Our study is a retrospective, observational study. The patients with AF and DM were divided into two groups: those using SGLT-2i or not using SGLT-2i, and 3-year follow-up results were examined. The endpoints of the study were defined as all-cause death, the development of myocardial infarction (MI), major bleeding requiring hospitalization, and an ischemic cerebrovascular event (CVE). Differences between groups according to SGLT-2i use were analyzed. Results The study included 485 patients, 205 (42.3%) of whom were male and had an average age of 70.7 ± 9.7 years. A total of 138 of 485 patients (28.5%) received SGLT-2i. All-cause mortality was lower in the group receiving SGLT-2i (p

Abstract Background Extracorporeal membrane oxygenation (ECMO) might be required as a treatment option in patients with critical pulmonary embolism (PE). However, the clinical features and outcomes of the use of ECMO for critical acute PE are still limited. The present study aimed to clarify the clinical characteristics, management strategies and outcomes of patients with acute PE requiring ECMO in the current era using data from a large-scale observational database. Methods We analyzed the data of the COMMAND VTE Registry-2: a physician-initiated, multicenter, retrospective cohort study enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). Among 2035 patients with acute symptomatic PE, there were 76 patients (3.7%) requiring ECMO. Results Overall, the mean age was 58.4 years, and 34 patients (44.7%) were men. Cardiac arrest or circulatory collapse at diagnosis was reported in 67 patients (88.2%). The 30-day incidence of all-cause death was 30.3%, which were all PE-related deaths. The 30-day incidence of major bleeding was 54.0%, and the vast majority of bleedings were procedure site-related bleeding events and surgery-related bleeding (22.4%). The 30-day incidence of all-cause death was 6.3% in 16 patients with surgical intervention, 43.8% in 16 patients with catheter intervention, 25.0% in 16 patients with thrombolytic therapy, and 39.3% in 28 patients with anticoagulation only. Conclusions The current large real-world VTE registry in Japan revealed clinical features and outcomes of critical acute PE requiring ECMO in the current era, which suggested several unmet needs for future clinical trials.

Background Methods Results Conclusions Data on patients aged 90 or older are rare. This study aims to describe clinical characteristics, treatment strategies, and clinical outcomes (rates of VTE recurrence, major bleeding, and mortality), during the first 3 months of anticoagulant treatment for VTE, depending on the treatment period.We analyzed data from RIETE, an ongoing global observational registry of patients with objectively confirmed acute VTE, grouped in 5‐year intervals (2004–2008, 2009–2013, 2014–2018, and 2019–2023).Among 3477 patients aged 90 or older, clinical characteristics have changed over time (less heart failure, more dementia), with an increase in PE diagnoses from 57% in 2004–2008 to 69% in 2019–2023 (p‐trends <0.001), but of lower severity. For long‐term therapy, there was an increase in patients receiving DOACs (p‐trends <0.001), with a decrease in patients on VKAs (p‐trends <0.001). Mortality and fatal PE respectively showed a temporal trend: 19% and 4% in 2004–2008 to 15% (p‐trends 0.026) and 2% (p‐trends 0.002) in 2019–2023. In multivariable analyses, fatal PE declined from 2004 to 2023 (HR: 0.91; 95% CI: 0.87–0.96). Compared with VKAs, receiving LMWH during the first 3 months of anticoagulation was associated with a higher risk of major bleeding (HR: 1.91; 95% CI: 1.16–3.14) and death (HR: 2.20; 95% CI: 1.71–2.82). The effect seems to be the opposite for DOACs (HR: 0.50; 95% CI: 0.20–1.30 for major bleeding; HR: 0.86; 95% CI: 0.57–1.28 for all‐cause death).Fatal PE declined from 2004 to 2023, despite an increase in the diagnosis of PE. Since the arrival of DOACs, there seems to be better management of the therapeutic and diagnostic aspects of VTE in this population, underlining the need for further research on patients aged 90 or older. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusions Systematic Review Registration Evidence‐based protocols for managing bleeding emergencies in patients with immune thrombocytopenia (ITP) are lacking. We conducted a systematic review of treatments for critical bleeding in patients with ITP.We included all study designs and extracted data in aggregate or individually for patients who received one or more interventions and for whom any of the following outcomes were reported: platelet count response, bleeding, disability, or death.We identified 49 eligible studies reporting 112 critical bleed patients with ITP, including 66 children (median age, 10 years), 36 adults (median age, 41.5 years), and 10 patients with unreported age. Patients received corticosteroids (n = 67), IVIG (n = 49), platelet transfusions (n = 41), TPO‐RAs (n = 17), and splenectomy (n = 28) either alone or in combination. Studies reported 29 different treatment combinations, the 5 most common were corticosteroids, platelet transfusion and splenectomy (n = 13), corticosteroids and IVIG (n = 13), or splenectomy alone (n = 13); IVIG alone (n = 11); and corticosteroids, IVIG and TPO‐RA (n = 8). Mortality among patients with critical bleeds in ITP was 30.6% for adults and 19.7% for children.The effects of individual treatments on patient outcomes were uncertain due to very low‐quality evidence. There is a need for a standardized approach to the treatment of ITP critical bleeds.CRD42020161206. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Anticoagulation therapy in patients with atrial fibrillation (AF) and concomitant cancer can be challenging due to the significantly increased risk of both embolism and bleeding. Moreover, the benefits and risks of vitamin K antagonists (VKA, eg. warfarin) versus non‐vitamin K antagonist oral anticoagulants (NOACs) in such patients are less well understood.From the prospective, global, multi‐centered Global Registry on Long‐Term Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA‐AF), we characterized these patients according to their history of prior cancer when enrolled. All patients received anticoagulant therapy. The primary outcome was the composite of all‐cause mortality, stroke, transient ischemic attack, systemic embolism. The secondary endpoints were all‐cause mortality, cardiovascular death, stroke, major bleeding and thromboembolism during the 3 years follow‐up period. Cox regression analyses were used to calculate the hazard ratio (HR) and confidence interval (CI) following propensity score matching (PSM).Overall, among 16,700 patients enrolled in Phase III in GLORIA‐AF, 1725 (10%) patients had concomitant cancer(s) at enrolment. After PSM, the primary outcome occurred in 250 (14.8%) of patients with cancer(s) and 160 (9.3%) without cancer(s) (HR, 1.62 [95% CI, 1.33–1.97], p < .001) during the 3 years follow‐up period. The risk of all‐cause mortality was significantly higher in patients with cancer(s) versus non‐ cancer(s) (HR, 1.71 [95% CI, 1.37–2.12], p < .001). In patients with cancer(s), after PSM, the use of NOACs was associated with reduced risk of the primary outcome compared with that of VKA (HR, .69 [95% CI, .49–.99], p = .043), as well as a lower risk of thromboembolism (HR, .49 [95% CI, .24–1.00], p = .051), but the risk of major bleeding was not significantly different (HR, .87 [95% CI, .48–1.56], p = .635). Subgroup analysis in patients with cancers showed a reduced risk of major bleeding with NOACs compared with VKA (HR, .18 [95% CI, .04–.8], p = .024) in patients with coronary artery disease (CAD). For the main cancer subtypes (genitourinary, breast, gastrointestinal, haematological and skin), the trends for the risk of primary outcome were consistently favouring NOACs compared with VKA without any significant interaction among these five cancers.Cancer is a common comorbidity in patients with AF and is associated with increased risk of composite of all‐cause mortality and thromboembolism. Compared with VKA, NOACs was associated with a lower risk of composite events and showed an advantage in lower risk of thromboembolism, as well as a reduced risk of major bleeding when CAD was also present. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) might be required as a treatment option in patients with critical pulmonary embolism (PE). However, the clinical features and outcomes of the use of ECMO for critical acute PE are still limited. The present study aimed to clarify the clinical characteristics, management strategies and outcomes of patients with acute PE requiring ECMO in the current era using data from a large-scale observational database. Methods: We analyzed the data of the COMMAND VTE Registry-2: a physician-initiated, multicenter, retrospective cohort study enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). Among 2035 patients with acute symptomatic PE, there were 76 patients (3.7%) requiring ECMO. Results: Overall, the mean age was 58.4 years, and 34 patients (44.7%) were men. Cardiac arrest or circulatory collapse at diagnosis was reported in 67 patients (88.2%). The 30-day incidence of all-cause death was 30.3%, which were all PE-related deaths. The 30-day incidence of major bleeding was 54.0%, and the vast majority of bleedings were procedure site-related bleeding events and surgery-related bleeding (22.4%). The 30-day incidence of all-cause death was 6.3% in 16 patients with surgical intervention, 43.8% in 16 patients with catheter intervention, 25.0% in 16 patients with thrombolytic therapy, and 39.3% in 28 patients with anticoagulation only. Conclusions: The current large real-world VTE registry in Japan revealed clinical features and outcomes of critical acute PE requiring ECMO in the current era, which suggested several unmet needs for future clinical trials. [ABSTRACT FROM AUTHOR]

Background: The optimal approach for anticoagulation in patients with bioprosthetic valves and atrial fibrillation (AF) remains a subject of debate. A meta-analysis using updated evidence to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) in patients with AF and bioprosthetic valves to address this controversy. Methods: A comprehensive search was conducted in multiple databases, including PubMed, Scopus, Web of Science, ProQuest, and the Cochrane Central Register of Controlled Trials, up until March 2023. The search aimed to identify relevant randomized controlled trials (RCTs) that examined the efficacy and safety outcomes of both direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with bioprosthetic valves and atrial fibrillation. The primary outcomes of interest were major bleeding and all-cause mortality. Results: Our study demonstrated that despite the difference was not significant, the hazard of all-cause mortality was 2.5% higher in the DOAC group (HR = 1.03, 95% CI = [0.88, 1.19], p-value =.75). Similarly, the hazard of stroke (HR = 1.03, 95% CI = [0.87, 1.32], p-value =.71) and major bleeding (HR = 1.11, 95% CI = [0.89, 1.38], p-value =.36) were found to be respectively 3.2 and 10.7% higher in the DOAC group, although the difference was not significant. However, the hazard of intracranial hemorrhage was found to be 28.8 lower in the DOAC treatment group (HR = 0.71, 95% CI = [0.39, 1.31], p-value =.27), which again was not statistically significant. Conclusions: Our meta-analysis demonstrates that in patients undergoing bioprosthetic valve surgery and presenting with AF afterward, DOAC and VKA are similar regarding life-threatening and all-cause mortality outcomes, including major bleeding, stroke, and intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

Patients with peripheral artery disease (PAD) who undergo lower extremity revascularization (LER) are at high risk for cardiovascular and limb-related ischemic events. The role of antithrombotic therapy is to prevent thrombotic complications, but this requires balancing increased risk of bleeding events. The dual pathway inhibition (DPI) strategy including aspirin and low-dose rivaroxaban after LER has been shown to reduce major adverse cardiovascular and limb-related events without significant differences in major bleeding. There is now a need to implement the broad adoption of DPI therapy in PAD patients who have undergone LER in routine practice. [ABSTRACT FROM AUTHOR]

Background: Some clinical characteristics and comorbidities in atrial fibrillation (AF) patients are exclusion criteria in randomized clinical trials (RCTs) investigating oral anticoagulants (OAC). However, these conditions are present also in everyday clinical practice patients. We compared the risk of adverse clinical outcomes between patients with and without RCT exclusion criteria. Methods: The Murcia AF Project II was an observational cohort study including AF outpatients starting vitamin K antagonists (VKAs) from July 2016 to June 2018. For the selection of the exclusion criteria, the four pivotal RCTs of direct-acting OAC (DOACs) were used as reference. During 2 years, all ischemic strokes/transient ischemic attacks, major adverse cardiovascular events (MACEs), major bleeds, and all-cause deaths were recorded. Results: 1050 patients (51.5% female, median age 77 years) were included, of whom 368 (35%) met at least one exclusion criterion for RCTs. During follow-up, the incidence rate ratios for major bleeding, MACE and all-cause mortality were higher among patients with exclusion criteria (all p < 0.001). Patients fulfilling at least one exclusion criterion had increased risks of major bleeding (aHR 1.48; 95% CI 1.22–1.81; p < 0.001), MACE (aHR 1.51, 95% CI 1.10–2.09, p = 0.012), and mortality (aHR 3.22, 95% CI 2.32–4.48, p < 0.001), as well as a lower event-free survival (all log-rank p < 0.001). Conclusions: In this AF cohort taking VKAs, more than one-third had at least one RCT exclusion criteria, which translates into higher risk of major bleeding, MACE, and death. These observations should be considered when translating RCTs results to AF patients for a proper and a more patient-centered management. [ABSTRACT FROM AUTHOR]

Abstract Background Oral anticoagulants (OAC) can reduce ischemic stroke/systemic embolism (SSE) in patients with non‐valvular atrial fibrillation (AF) while increasing the risk of major bleeding. We aimed to analyze the number needed to treat for the net benefit (NNTnet) of warfarin and non‐vitamin K antagonist oral anticoagulants (NOACs). Methods We analyzed the results from multicenter national AF registry from 27 hospitals in Thailand. Follow‐up data were collected every 6 months until 3 years. Main outcomes were SSE, major bleeding, and intracranial hemorrhage (ICH). NNT was calculated from the absolute risk reduction (ARR) of SSE or absolute risk increase (ARI) of major bleeding or ICH. We compared NNTnet of warfarin versus no OAC, NOACs versus no OAC, and NOACs versus warfarin. Warfarin was also categorized into time in therapeutic range (TTR) < and ≥65%. Results We studied a total of 3405 patients (mean age 67.8 ± 11.3 years, 1424 (41.8%) were female). The incidence rates of SSE, major bleeding, and ICH were 1.51, 2.25, and 0.78 per 100 person‐years, respectively. Warfarin had negative NNTnet −37 compared to no OAC. NOACs had positive NNTnet 101 and 27 compared to no OACs and warfarin. Warfarin with TTR 65% had positive NNTnet 42 compared to no OAC. NOACs had comparable NNTnet as warfarin with TTR ≥65%. Conclusion Warfarin had a negative NNTnet compared to no OAC. Only warfarin with TTR 65% has positive NNTnet. NOACs had positive NNTnet compared to no OAC and when compared to warfarin.

This is a retrospective descriptive study carried out on 1036 patients with nonvalvular atrial fibrillation who took oral anticoagulants and visited the cardiology clinic of the University of Medicine and Pharmacy Hospital, Ho Chi Minh City, from 01/01/2021 to 30/06/2021. The objective was to investigate the incidence of bleeding in these patients. The average age of the study population was 72±12 years, with an average CHA2DS2VASc score of 4.2±1.8 and an average HAS-BLED score of 1.26±0.03. Rivaroxaban was the most prescribed anticoagulant, with a total of 463 cases, accounting for 44.7%. There were 99 bleeding events recorded; of these, 37 (37.4%) cases were severe bleeding, and 62 (62.6%) were minor bleeding. Gastrointestinal bleeding was the most common site in both severe and minor bleeding groups. The group who had an overdose of anticoagulants had a severe bleeding rate of 52.4%, similar to the group whose anticoagulant dose could not be assessed (55.6%), nearly twice as high as the group who took the standard dose (30.6%) and the group who took a lower dose than recommended (30.0%). Of the 37 cases of severe bleeding, 14 (37.8%) were using rivaroxaban, 12 (32.4%) were using vitamin K antagonists, 5 (13.5%) were using dabigatran, and 6 (16.2%) were using a combination of anticoagulants and antiplatelets. To conclude, gastrointestinal bleeding was a very common event in patients using anticoagulants for nonvalvular atrial fibrillation. Non-vitamin K antagonist oral anticoagulants should be preferred in patients with a high risk of bleeding (dabigatran may have advantages over rivaroxaban). It is important to assess the patient’s weight and renal function to determine the appropriate anticoagulant dose according to recommendations to reduce the risk of severe bleeding.

Background and Aims Patients with high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) are at increased risk of not only bleeding, but also ischaemic events. This study aimed to determine the long-term relative risk of ischaemic and bleeding events in HBR patients. Methods This study was a nationwide cohort study, based on the Korean National Health Insurance Review and Assessment Service database. Patients diagnosed with stable angina or acute coronary syndrome and those who underwent PCI in Korea between 2009 and 2018 were included in the analysis. According to the Academic Research Consortium HBR criteria, the total population was divided into HBR and non-HBR groups. The co-primary outcomes were major bleeding events and ischaemic (composite of cardiac death, myocardial infarction, and ischaemic stroke) events. Results Among a total of 325 417 patients who underwent PCI, 66 426 patients (20.4%) had HBR. During the follow-up period, HBR patients had a higher risk for major bleeding events (23.9% vs. 8.9%, P <.001) and ischaemic events (33.8% vs. 14.4%, P <.001). However, the impact of HBR was significant for major bleeding events [hazard ratio (HR) 3.12, 95% confidence interval (CI) 3.04–3.21, P <.001] and for ischaemic events (HR 2.50, 95% CI 2.45–2.56, P <.001). The HBR group was also associated with a greater risk of all-cause mortality (HR 3.73, 95% CI 3.66–3.79, P <.001). The average annual rate of major bleeding events within the first year after PCI was 5.5% for a single major criterion, and 2.9% for a single minor criterion. Conclusions Among patients undergoing PCI, those with HBR were at increased long-term risk for both bleeding and ischaemic events, with a greater risk of mortality compared to non-HBR patients. [ABSTRACT FROM AUTHOR]

Patients with immune thrombocytopenia (ITP) admitted for non-ST elevation myocardial infarction (NSTEMI) present a unique therapeutic challenge due to the increased risk of bleeding with antiplatelet and anticoagulation therapies. There is limited evidence studying hospital mortality and complications in this population. The study included a patient cohort from the 2018–2021 National Inpatient Sample database. Propensity score matched NSTEMI patients with and without ITP using a 1:1 matching ratio. Outcomes analyzed were in-hospital mortality, rates of diagnostic angiogram, percutaneous coronary intervention (PCI), acute kidney injury (AKI), congestive heart failure (CHF), cardiogenic shock, cardiac arrest, mechanical ventilation, tracheal intubation, ventricular tachycardia (VT), ventricular fibrillation (VF), major bleeding, need for blood and platelet transfusion, length of stay (LOS), and total hospitalization charges. A total of 1,699,020 patients met inclusion criteria (660,490 females [39%], predominantly Caucasian 1,198,415 (70.5%); mean [SD] age 67, [3.1], including 2,615 (0.1%) patients with ITP. Following the propensity matching, 1,020 NSTEMI patients with and without ITP were matched. ITP patients had higher rates of inpatient mortality (aOR 1.98, 95% CI 1.11–3.50, p 0.02), cardiogenic shock, AKI, mechanical ventilation, tracheal intubation, red blood cells and platelet transfusions, longer LOS, and higher total hospitalization charges. The rates of diagnostic angiogram, PCI, CHF, VT, VF, and major bleeding were not different between the two groups. Patients with ITP demonstrated higher odds of in-hospital mortality for NSTEMI and need for platelet transfusion with no difference in rates of diagnostic angiogram or PCI. [ABSTRACT FROM AUTHOR]

Aims Compliance with integrated care based on the Atrial fibrillation Better Care (ABC) pathway has been associated with improved clinical outcomes. The primary objective of this study was to compare clinical outcomes of AF patients according to the compliant status of each component of the ABC pathway in a hierarchical win ratio approach. Methods and results We studied AF patients in the COOL-AF registry. Each patient was followed every 6 months until 3 years. A win ratio analysis was performed, as not all clinical outcomes are equivalent. The hierarchical outcomes were (1) all-cause death, (2) intracranial haemorrhage (ICH), (3) ischaemic stroke/systemic embolism, (4) non-ICH major bleedings, and (5) acute myocardial infarction or heart failure. We also assessed win ratio and win proportion variance over the follow-up time, and the variations over time. A total of 3405 patients (mean age 67.8 ± 11.3; 41.8% female) were studied. Win ratio of ABC-compliant (all three components) vs. ABC-not-compliant was 1.57 (1.35–1.83), P < 0.001. When adding time in therapeutic range (TTR) data for compliant criteria for those who were on warfarin, the win ratio increased to 2.28 (1.89–2.75), P < 0.001. The A-compliant group (plus TTR data), B-compliant, and C-compliant had the win ratio of 1.81 (1.51–2.12), 1.82 (1.53–2.16), and 1.39 (1.18–1.62), all P < 0.001, compared to not compliant group. Conclusion Management of AF patients according to each component of the ABC pathway is associated with better clinical outcomes compared to those non-compliant to ABC pathway. This finding underscores the importance of a holistic management approach strategy for AF patients. [ABSTRACT FROM AUTHOR]

Background: Treating cancer-associated venous thromboembolism (CAT) with anticoagulation prevents recurrent venous thromboembolism (rVTE), but increases bleeding risk. Objectives: To compare incidence of rVTE, major bleeding, and all-cause mortality for rivaroxaban versus low molecular weight heparin (LMWH) in patients with CAT. Methods: We developed a cohort study using Swedish national registers 2013–2019. Patients with CAT (venous thromboembolism within 6 months of cancer diagnosis) were included. Those with other indications or with high bleeding risk cancers were excluded (according to guidelines). Follow-up was from index-CAT until outcome, death, emigration, or end of study. Incidence rates (IR) per 1000 person-years with 95% confidence interval (CI) and propensity score overlap-weighted hazard ratios (HRs) for rivaroxaban versus LMWH were estimated. Results: We included 283 patients on rivaroxaban and 5181 on LMWH. The IR for rVTE was 68.7 (95% CI 40.0–109.9) for rivaroxaban, compared with 91.6 (95% CI 81.9–102.0) for LMWH, with adjusted HR 0.77 (95% CI 0.43–1.35). The IR for major bleeding was 23.5 (95% CI 8.6–51.1) for rivaroxaban versus 49.2 (95% CI 42.3–56.9) for LMWH, with adjusted HR 0.62 (95% CI 0.26–1.49). The IR for all-cause mortality was 146.8 (95% CI 103.9–201.5) for rivaroxaban and 565.6 (95% CI 541.8–590.2) for LMWH with adjusted HR 0.48 (95% CI 0.34–0.67). Conclusions: Rivaroxaban performed similarly to LMWH for patients with CAT for rVTE and major bleeding. An all-cause mortality benefit was observed for rivaroxaban which potentially may be attributed to residual confounding. Trial registration number: NCT05150938 (Registered 9 December 2021). Highlights: Treating cancer-associated venous thromboembolism with anticoagulation prevents recurrent VTE, but may increase the risk of bleeding. DOACs have easier administration and proven higher treatment adherence compared to LMWH. Excluding cancer with high risk of bleeding, rivaroxaban performed similarly to LMWH for patients with cancer and VTE for recurrent VTE and major bleeding. An all-cause mortality benefit was observed for rivaroxaban compared to LMWH which potentially may be attributed to residual confounding. [ABSTRACT FROM AUTHOR]

Purpose: Bleeding is an important health outcome of interest in epidemiological studies. We aimed to develop and validate rule‐based algorithms to identify (1) major bleeding and (2) all clinically relevant bleeding (CRB) (composite of major and all clinically relevant nonmajor bleeding) within real‐world electronic healthcare data. Methods: We took a random sample (n = 1630) of inpatient admissions to Singapore public healthcare institutions in 2019 and 2020, stratifying by hospital and year. We included patients of all age groups, sex, and ethnicities. Presence of major bleeding and CRB were ascertained by two annotators through chart review. A total of 630 and 1000 records were used for algorithm development and validation, respectively. We formulated two algorithms: sensitivity‐ and positive predictive value (PPV)‐optimized algorithms. A combination of hemoglobin test patterns and diagnosis codes were used in the final algorithms. Results: During validation, diagnosis codes alone yielded low sensitivities for major bleeding (0.16) and CRB (0.24), although specificities and PPV were high (>0.97). For major bleeding, the sensitivity‐optimized algorithm had much higher sensitivity and negative predictive values (NPVs) (sensitivity = 0.94, NPV = 1.00), however false positive rates were also relatively high (specificity = 0.90, PPV = 0.34). PPV‐optimized algorithm had improved specificity and PPV (specificity = 0.96, PPV = 0.52), with little reduction in sensitivity and NPV (sensitivity = 0.88, NPV = 0.99). For CRB events, our algorithms had lower sensitivities (0.50–0.56). Conclusions: The use of diagnosis codes alone misses many genuine major bleeding events. We have developed major bleeding algorithms with high sensitivities, which can ascertain events within populations of interest. [ABSTRACT FROM AUTHOR]

ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation) demonstrated that apixaban, compared with aspirin, significantly reduced stroke and systemic embolism (SE) but increased major bleeding in patients with subclinical atrial fibrillation. To help inform decision making, the authors evaluated the efficacy and safety of apixaban according to baseline CHA 2 DS 2 -VASc score. We performed a subgroup analysis according to baseline CHA 2 DS 2 -VASc score and assessed both the relative and absolute differences in stroke/SE and major bleeding. Baseline CHA 2 DS 2 -VASc scores were <4 in 1,578 (39.4%) patients, 4 in 1,349 (33.6%), and >4 in 1,085 (27.0%). For patients with CHA 2 DS 2 -VASc >4, the rate of stroke was 0.98%/year with apixaban and 2.25%/year with aspirin; compared with aspirin, apixaban prevented 1.28 (95% CI: 0.43-2.12) strokes/SE per 100 patient-years and caused 0.68 (95% CI: −0.23 to 1.57) major bleeds. For CHA 2 DS 2 -VASc <4, the stroke/SE rate was 0.85%/year with apixaban and 0.97%/year with aspirin. Apixaban prevented 0.12 (95% CI: −0.38 to 0.62) strokes/SE per 100 patient-years and caused 0.33 (95% CI: −0.27 to 0.92) major bleeds. For patients with CHA 2 DS 2 -VASc =4, apixaban prevented 0.32 (95% CI: −0.16 to 0.79) strokes/SE per 100 patient-years and caused 0.28 (95% CI: −0.30 to 0.86) major bleeds. One in 4 patients in ARTESiA with subclinical atrial fibrillation had a CHA 2 DS 2 -VASc score >4 and a stroke/SE risk of 2.2% per year. For these patients, the benefits of treatment with apixaban in preventing stroke/SE are greater than the risks. The opposite is true for patients with CHA 2 DS 2 -VASc score <4. A substantial intermediate group (CHA 2 DS 2 -VASc =4) exists in which patient preferences will inform treatment decisions. (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; NCT01938248) [ABSTRACT FROM AUTHOR]

Aims: Our aims were to describe the clinical characteristics, adverse clinical events, healthcare resource utilization (HCRU) and costs of patients with major bleeding during direct Factor Xa inhibitor (FXai) use. Methods: This is a retrospective cohort study that included secondary data from computerized health records of seven Spanish Autonomous Communities. Patients with a first major bleeding during treatment with a direct FXai were analyzed during a 3-year period. Results: Of 8972 patients taking a direct FXai, 470 (5.24%) had major bleeding (mean age (SD) 77.93 (9.71) years, 61.06% women). The most frequent indications for using FXais were atrial fibrillation (78.09%) and venous thromboembolism (17.66%). Among those with major bleeding, 88.94% presented with gastrointestinal bleeding, 6.81% intracranial bleeding, 2.13% trauma-related bleeding and 4.26% other major bleeding. Prothrombin complex concentrates were used in 63.19%, followed by transfusion of blood products (20.21%) and Factor VIIa (7.66%). In total, 4.26% of patients died in the hospital due to the first major bleeding. At the study end (after 3-year follow-up), 28.94% of the patients had died, 12.34% had a myocardial infarction and 9.15% an ischemic stroke. At year 3, overall bleeding cost was EUR 5,816,930.5, of which 79.74% accounted for in-hospital costs to treat the bleeding episode. Conclusions: Despite the use of replacement agents being high, major events were common, with a 29% mortality at the end of the follow up, and HCRU and costs were high, evidencing the need for new reversal treatment strategies. [ABSTRACT FROM AUTHOR]

BackgroundThrombocytopenia is often associated with adverse outcomes in patients with atrial fibrillation. Therefore, we conducted a meta-analysis to comprehensively assess the impact of thrombocytopenia on ischemic stroke/systemic embolism, major bleeding and all-cause mortality in patients with atrial fibrillation.MethodsTwo electronic databases, PubMed and Web of Science, were systematically searched from their inception to December 1, 2023, including the studies on the correlation between atrial fibrillation patients with thrombocytopenia and adverse outcomes. Relevant data was extracted, literature quality was evaluated, meta-analysis was performed by using REVMAN 5.4 software, and the results were reported with odds ratio (OR) of 95% confidence interval (CI).ResultsA total of 12 studies included 73,824 patients with atrial fibrillation (average age: 72.67, males: 42,275, 57.3%), among them, there were 7,673 patients combined with thrombocytopenia. The average follow-up time of these studies was 87 days to 55 months. Compared to no thrombocytopenia, atrial fibrillation patients combined with thrombocytopenia have a significant risk reduction of ischemic stroke/systemic embolism [OR: 0.79, 95% CI: (0.69, 0.91); P

Background: The bleeding risk of patients with atrial fibrillation (AF) changes over time. Most studies thus far evaluated only the baseline bleeding risk with discordant results. The impact of incident thrombocytopenia during direct oral anticoagulant (DOAC) therapy and its relation to bleeding has not been previously investigated. Objectives: To investigate the incidence rate of thrombocytopenia and major bleeding (MB) risk in AF patients on DOACs. Methods: Prospective ongoing ATHEROsclerosis in Atrial Fibrillation study including patients with nonvalvular AF on DOACs. Incident thrombocytopenia was defined as a platelet count

To evaluate the safety of cangrelor administered concurrently with heparin or bivalirudin in patients on mechanical circulatory support. A single-center, retrospective cohort study of adult patients consecutively admitted between January 2016 and October 2020. A tertiary medical center. Adult patients admitted to the cardiovascular intensive care unit put on mechanical circulatory support for acute myocardial infarction (AMI) or non-AMI indications. Patients who received cangrelor underwent percutaneous coronary intervention with stenting during the index event or within the last year. None. The primary outcome was the incidence of major bleeding, defined by the Extracorporeal Life Support Organization criteria, in patients with mechanical circulatory support receiving cangrelor plus anticoagulation with heparin or bivalirudin with or without aspirin versus patients who did not receive cangrelor. Sixty-eight patients were included in the study. Twenty-nine patients received cangrelor, and 39 did not. Cangrelor was not associated with an increase in major bleeding; however, the CI was wide (adjusted hazard ratio 1.93, 95% CI 0.61-6.11; p = 0.262). Patients receiving cangrelor did not appear to be at higher risk of major bleeding compared to patients not receiving cangrelor. Larger trials should be conducted to better evaluate the safety of cangrelor in patients with mechanical circulatory support. [ABSTRACT FROM AUTHOR]

Purpose: Outcomes from randomized controlled trials (RCTs) inform the latest recommendations on percutaneous coronary intervention (PCI) management of a short period of oral anticoagulation (OAC), a P2Y12 receptor inhibitor, and aspirin for 1 week or until hospital discharge in patients with atrial fibrillation (AF) undergoing PCI, and up to 4 weeks in individuals considered to be at high-risk for ischemic events, followed by discontinuation of aspirin and continuation of OAC and a P2Y12 inhibitor for up to 12 months. Methods: We examined and summarized the outcomes of bleeding and major adverse cardiac events (MACEs) from RCTs and meta-analyses, published between 2013 and 2022, comparing therapy with OAC and a P2Y12 inhibitor with and without aspirin in AF patients undergoing PCI with stenting. Results: Data comparing dual therapy with OAC and a P2Y12 inhibitor alone to triple therapy with OAC, a P2Y12 inhibitor, and aspirin with respect to the risks of MACEs, including stent thrombosis within the first 30 days, are underpowered and inconclusive. The addition of aspirin does not appear to be associated with a decreased risk of ischemic events, even in patients with high-risk CHA2DS2-VASc scores, but does significantly increase bleeding hazards. The increased safety of newer generation drug-eluting stents may have further minimized any theoretical anti-ischemic benefits of aspirin. The possible attenuation of the pleiotropic effects of concomitant cardiovascular medications by aspirin may also have been a contributing factor. Conclusion: The addition of aspirin to OAC and a P2Y12 inhibitor is likely associated with a net clinical harm in patients with AF who undergo PCI with stenting, even within the first 1–4 weeks after PCI. Revisiting the guideline recommendations to administer aspirin in this timeframe may be warranted. [ABSTRACT FROM AUTHOR]

Previous meta‐analyses assessed andexanet alfa (AA) or prothrombin complex concentrate (PCC) products for the treatment of Factor Xa inhibitor (FXaI)‐associated major bleeding. However, they did not include recent studies or assess the impact of the risk of bias. We conducted a systematic review with meta‐analysis on the effectiveness of AA versus PCC products for FXaI‐associated major bleeding, inclusive of the studies' risk of bias. PubMed and Embase were searched for comparative studies assessing major bleeding in patients using FXaI who received AA or PCC. We used the Methodological Index for NOn‐Randomized Studies (MINORS) checklist and one question from the Joanna Briggs Institute (JBI) Critical Appraisal of Case Series tool to assess the risk of bias. Random‐effects meta‐analyses were performed to provide a pooled estimate for the effect of AA versus PCC products on hemostatic efficacy, in‐hospital mortality, 30‐day mortality, and thrombotic events. Low–moderate risk of bias studies were meta‐analyzed separately, as well as combined with high risk of bias studies. Eighteen comparative evaluations of AA versus PCC were identified. Twenty‐eight percent of the studies (n = 5) had low–moderate risk and 72% (n = 13) had a high risk of bias. Studies with low–moderate risk of bias suggested improvements in hemostatic efficacy [Odds Ratio (OR) 2.72 (95% Confidence Interval (CI): 1.15–6.44); one study], lower in‐hospital mortality [OR 0.48 (95% CI: 0.38–0.61); three studies], and reduced 30‐day mortality [OR 0.49 (95% CI: 0.30–0.80); two studies] when AA was used versus PCC products. When studies were included regardless of the risk of bias, pooled effects showed improvements in hemostatic efficacy [OR 1.36 (95% CI: 1.01–1.84); 12 studies] and reductions in 30‐day mortality [OR 0.53 (95% CI: 0.37–0.76); six studies] for AA versus PCC. The difference in thrombotic events with AA versus PCC was not statistically significant in the low–moderate, high, or combined risk of bias groups. The evidence from low–moderate quality real‐world studies suggests that AA is superior to PCC in enhancing hemostatic efficacy and reducing in‐hospital and 30‐day mortality. When studies are assessed regardless of the risk of bias, the pooled hemostatic efficacy and 30‐day mortality risk remain significantly better with AA versus PCC. [ABSTRACT FROM AUTHOR]

Background: This systematic review aims to evaluate and compare differences in clinical outcomes for adult patients diagnosed with ISSPE who were managed with anticoagulation vs clinical surveillance. Methods: PubMed, Embase, ProQuest, Cochrane, and Google Scholar were searched to identify studies evaluating the use of anticoagulation and/or clinical surveillance in patients diagnosed with ISSPE. The search included studies published up to August 3, 2023. Outcomes of interest included 90-day recurrent venous thromboembolism (VTE), major bleeding, and all-cause mortality rates. Results: Ten studies were included with a total of 1224 patients. Of these patients, 791 were treated with anticoagulation and 433 underwent surveillance. Studies found no difference in recurrent VTE rates, with the majority of studies reporting no recurrence. Of the studies that reported VTE recurrence, rates were.5% to 1.4% for the anticoagulation groups and 3.1% to 3.2% for the surveillance groups. Major bleeding rates were also similar. In anticoagulated patients, major bleeding rates ranged from 1% to 10%. In clinical surveillance patients, the majority found no rate of major bleeding, with 2 studies reporting rates of.8% to 3.2%. Mortality rates ranged widely with no significant differences reported. Conclusion: Clinical surveillance appears to be a safe and effective alternative to anticoagulation in patients with ISSPE. Ninety-day rates of recurrent VTE, major bleeding, and mortality were comparable between groups. These findings highlight the need for updated practice management guidelines to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Polypharmacy is commonly observed in atrial fibrillation (AF) and is associated with poorer clinical outcomes. Our study aimed to elucidate the polypharmacy prevalence, its associated risk factors, and its relationship with adverse clinical outcomes using a 'real-world' database. Methods: This study included 451,368 subjects without prior history of AF (median age, 54 [interquartile range, 48.0-63.0] years; 207,748 [46.0%] female) from the Korea National Health Insurance Service-Health Screening (NHIS-HealS) database between 2002 and 2013. All concomitant medications prescribed were collected, and the intake of five or more concomitant drugs was defined as polypharmacy. During the follow-up, all-cause death, major bleeding events, transient ischemic attack (TIA) or ischemic stroke, and admission due to worsened heart failure were recorded. Results: Based on up to 7.7 (6.8-8.3) years of follow-up and 768,306 person-years, there were 12,241 cases of new-onset AF identified. Among patients with new-onset AF (40.0% females, median age 63.0 [54.0-70.0] years), the polypharmacy prevalence was 30.9% (3784). For newly diagnosed AF, factors, such as advanced age (with each increase of 10 years, odds ratios (OR) 1.32, 95% confidence interval (CI) 1.26-1.40), hypertension (OR 4.00, 95% CI 3.62-4.43), diabetes mellitus (OR 3.25, 95% CI 2.86-3.70), chronic obstructive pulmonary disease (COPD) (OR 3.00, 95% CI 2.51-3.57), TIA/ischemic stroke (OR 2.36, 95% CI 2.03-2.73), dementia history (OR 2.30, 95% CI 1.06-4.98), end-stage renal disease (ESRD) or chronic kidney disease (CKD) (OR 1.97, 95% CI 1.38-2.82), and heart failure (OR 1.95, 95% CI 1.69-2.26), were found to be independently correlated with the incidence of polypharmacy. Polypharmacy significantly increased the incidence and risk of major bleeding (adjusted hazard ratio (aHR) 1.26, 95% CI 1.12-1.41). The study observed a statistically significant increase in the incidence of all-cause mortality, however, the risk for all-cause mortality elevated but did not show significance (aHR 1.11, 95% CI 0.99-1.24). The risk of stroke and admission for heart failure did not change with polypharmacy. Conclusions: In our investigation using data from a nationwide database, polypharmacy was widespread in new-onset AF population and was related to major bleeding events. However, polypharmacy does not serve as an independent risk factor for adverse outcomes, with exception of major bleeding event. For AF patients, ensuring tailored medication for comorbidities as well as reducing polypharmacy are essential considerations. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke (AIS) is the most common type of stroke and requires immediate reperfusion. Current acute reperfusion therapies comprise the administration of intravenous thrombolysis and/or endovascular thrombectomy. Although these acute reperfusion therapies are increasingly successful, optimized secondary antithrombotic treatment remains warranted, specifically to reduce the risk of major bleeding complications. In the development of AIS, coagulation and platelet activation play crucial roles by driving occlusive clot formation. Recent studies implicated that the intrinsic route of coagulation plays a more prominent role in this development, however, this is not fully understood yet. Next to the acute treatments, antithrombotic therapy, consisting of anticoagulants and/or antiplatelet therapy, is successfully used for primary and secondary prevention of AIS but at the cost of increased bleeding complications. Therefore, better understanding the interplay between the different pathways involved in the pathophysiology of AIS might provide new insights that could lead to novel treatment strategies. This narrative review focuses on the processes of platelet activation and coagulation in AIS, and the most common antithrombotic agents in primary and secondary prevention of AIS. Furthermore, we provide an overview of promising novel antithrombotic agents that could be used to improve in both acute treatment and stroke prevention. • Intrinsic activation is suggested to have a prevalent role in acute ischemic stroke. • Current anticoagulant therapies are associated with up to 10 % of major bleedings. • Current anticoagulant therapies are associated with up to 2 % of hemorrhagic strokes. • New antithrombotic therapies are needed for primary and secondary prevention of AIS. [ABSTRACT FROM AUTHOR]

Calcific aortic stenosis is the principal indication for transcatheter aortic valve replacement (TAVR). Comorbid mitral annular calcification (MAC) is often present in patients undergoing TAVR. Limited data exist on the impact of MAC on TAVR outcomes. We conducted a systematic review and meta-analysis to explore the effects of MAC and concomitant mitral valve dysfunction (MVD) on TAVR outcomes. A comprehensive literature review was conducted using PubMed, Embase, Google Scholar, ClinicalTrials.gov, Scopus, and OVID for studies until March 20, 2023. Using the random-effects Mantel-Haenszel method, we calculated pooled risk ratios (RRs) and their corresponding 95 % confidence intervals (CIs) for all dichotomous variables. Six studies comprising 5822 patients (2541 with MAC [severe MAC (>4 mm thickness) 583; non-severe MAC 1958; 400 with MVD; and 1071 without MVD], 3281 without MAC) met inclusion criteria. At 30 days and 1 year, no significant differences were observed between the overall MAC and no MAC groups in terms of mortality, stroke, and permanent pacemaker implantation. However, MAC with MVD was associated with a higher risk of all-cause mortality compared to MAC without MVD at 30 days (RR = 3.43, 95 % CI 2.04–5.76, P < 0.00001) and at 1 year (RR = 2.44, 95 % CI 1.85–3.20, P < 0.00001). Moreover, the risk of cardiovascular mortality was higher in patients with MAC and MVD compared to those with MAC alone (RR = 2.77, 95 % CI 1.89–4.06, P < 0.00001). Additionally, patients with severe MAC had a higher risk of major bleeding at 30 days compared to the non-severe MAC group (RR = 1.33, 95 % CI 1.04–1.69, P = 0.02). TAVR appears to be safe in patients with non-severe MAC, but severe MAC is associated with a higher risk of major bleeding and concomitant MVD increases the mortality risk in patients undergoing TAVR. [Display omitted] • This study explores the impact of mitral annular calcification (MAC) and concomitant mitral valve dysfunction (MVD) on transcatheter aortic valve replacement (TAVR) outcomes. • Severe MAC was associated with a higher risk of major bleeding, while MAC with MVD increased the risk of all-cause and cardiovascular mortality. • TAVR was generally safe for patients with non-severe MAC. • The findings of this review highlight the importance of evaluating for MVD in patients with MAC undergoing pre-TAVR workup. [ABSTRACT FROM AUTHOR]

The OAC3-PAD score was developed to predict bleeding risk in patients with lower extremity peripheral arterial disease (PAD), but its performance in concomitant international cohorts is largely unknown. This study aimed to validate the OAC3-PAD score in an unselected nationwide population of patients undergoing invasive treatment for symptomatic PAD. This was a nationwide cohort study including all patients who underwent a first revascularisation procedure or major amputation for symptomatic PAD in Denmark from 2000 – 2021. The study population was stratified based on OAC3-PAD score, and the one year risk of major bleeding was assessed, accounting for the competing risk of death. The score performance was evaluated using calibration plots, C statistic, Brier score, and the index of prediction accuracy (IPA). A total of 52 016 patients were included (mean age 71 years, 43.8% female). The one year risk of major bleeding increased with higher OAC3-PAD score, ranging from 1.6% (95% confidence interval [CI] 1.4 – 1.8%) to 2.3% (95% CI 2.0 – 2.5%), 3.5% (95% CI 3.2 – 3.8%), and 5.2% (95% CI 4.8 – 5.6%) for patients with low, low moderate, moderate high, and high score, respectively. Using patients with low risk as reference, the OAC3-PAD score effectively categorised patients, demonstrating statistically significant differences in bleeding risk across strata. However, the score showed modest discriminative performance, with a C statistic of 65% (95% CI 63 – 66%) and a Brier score of 2.6% (95% CI 2.5 – 2.7%). Nevertheless, it performed significantly better than the null model, as indicated by an IPA of 3.1%. Among patients who underwent invasive treatment for symptomatic PAD in routine care, the OAC3-PAD score was associated with greater risk of major bleeding with increasing score level. However, its discriminatory ability was modest, and the clinical utility remains to be determined. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) are the preferred treatment for venous thromboembolism (VTE). However, DOAC use in patients with a BMI greater than 40 kg/m2 has not been well studied despite the growing prevalence of obesity, and current literature is often underpowered. Methods: This multicenter, retrospective, observational study evaluated patients 18 years and older who received DOACs for acute VTE treatment. Patients receiving DOACs for recurrent VTE or for failure of another agent were excluded. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding within 12 months (or one month after stopping anticoagulation therapy). A propensity score analysis was performed to balance patient characteristics and evaluate the primary endpoints by BMI group. Time-to-event outcomes were analyzed using weighted Kaplan-Meier curves. Results: There were 165 patients with a BMI of at least 40 kg/m2 and 320 patients with a BMI less than 40 kg/m2. The majority received apixaban (373, 77%). Recurrent VTE occurred in 5 (3.0%) and 13 (4.1%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 0.66; 95% CI: 0.16–2.69). Major bleeding occurred in 5 (3.0%) and 15 (4.7%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 1.19; 95% CI: 0.36–3.92). Conclusion: There was no significant difference in VTE recurrence or major bleeding related to BMI among patients treated with DOACs. This study showed that DOACs may be a safe and effective VTE treatment option in patients with obesity. Key points: Data supporting the use of direct oral anticoagulants (DOACs) for the treatment of venous thromboembolism (VTE) in patients with obesity are limited. This multicenter analysis aimed to evaluate the effectiveness and safety of DOACs in patients with and without obesity. The majority of patients received apixaban. VTE recurrence and rates of major bleeding were not different between patients with a BMI of at least 40 kg/m2 compared to a BMI less than 40 kg/m2. This study adds to the growing body of evidence supporting the use of DOACs, particularly apixaban, in patients with obesity, although future prospective trials and additional data in patients at extremes of body weight will be useful. [ABSTRACT FROM AUTHOR]

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Background There have been limited data on the changes in clinical outcomes after the introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in real clinical practice. We evaluated the changes in management strategies and long‐term outcomes from the warfarin era to the DOAC era. Methods and Results We compared the 2 series of multicenter COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registries in Japan enrolling consecutive patients with acute symptomatic VTE: Registry 1: 3027 patients in the warfarin era (2010–2014) and Registry 2: 5197 patients in the DOAC era (2015–2020). The prevalence of DOAC use increased more in Registry 2 than in the Registry 1 (Registry 1: 2.6% versus Registry 2: 79%, P

In the European Guideline on Management of Major Bleeding and Coagulopathy Following Trauma updated recently, there are 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points, including initial resuscitation and prevention of further bleeding, diagnosis and monitoring of bleeding, rapid control of bleeding, initial management of bleeding and coagulopathy, further goal-directed coagulation management, management of antithrombotic agents, thromboprophylaxis, guideline implementation and quality control, as welll as the management of tissue oxygenation, volume, fluids and temperature. In this paper, we introduce the recommendations and rationale of the guideline and add some newly published clinical study evidence. These information would be very helpful to the development and training of the guidelines or protocols for the management of the trauma patient with major haemorrhage and coagulopathy in China.

Abstract Background Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. Methods A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45–60 kg, 80 mg for 61–100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4–0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). Results Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8–16) vs 14 (11–21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups. Conclusions Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. Trial registration The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.