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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]

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]

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: 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]

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]

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.

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]

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: 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]

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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]

• There is substantial heterogeneity in the risk of VTE in acute medically ill patients. • History of VTE and cancer related hospitalization represent profiles with a high risk of VTE. • Enoxaparin prophylaxis mostly ended at, or 1–2 days before hospital discharge. • More than 90 % of VTE events occurred while not on background prophylaxis. We aimed to describe the event rates and risk-factors for symptomatic venous thromboembolism (VTE) and major bleeding in a population of hospitalized acutely ill medical patients. Patients ≥40 years old and hospitalized for acute medical illness who initiated enoxaparin prophylaxis were selected from the US Optum research database. Rates of symptomatic VTE and major bleeding at 90-days were estimated via the Kaplan-Meier (KM) method. Risk factors were identified via the Cox proportional hazards model. A total of 123,022 patients met the selection criteria. The KM rates of VTE and major bleeding at 90-days were 3.5 % and 2.2 %, respectively. Among subgroups, the risk of VTE varied from 3.0 % in patients with ischemic stroke to 6.9 % in patients with a cancer-related hospitalization, and the risk of major bleeding varied from 1.9 % in patients with inflammatory conditions to 3.6 % in patients with ischemic stroke. Key risk factors for VTE were prior VTE (HR=4.15, 95 % confidence interval [CI] 3.80–4.53), cancer-related hospitalization (HR=2.35, 95 % CI 2.10–2.64), and thrombophilia (HR=1.64, 95 % CI 1.29–2.08). Key risk factors for major bleeding were history of major bleeding (HR=2.17, 95 % CI 1.72–2.74), history of non-major bleeding (HR=2.46, 95 % CI 2.24–2.70), and hospitalization for ischemic stroke (2.42, 95 % CI 2.11–2.78). There is substantial heterogeneity in the event rates for VTE and major bleeding in acute medically ill patients. History of VTE and cancer related hospitalization represent profiles with a high risk of VTE, where continued VTE prophylaxis may be warranted. [ABSTRACT FROM AUTHOR]

Introduction: Bleeding after heart valve surgery is a serious clinical challenge. Hypocalcemia has been associated with the extent of bleeding in patients with spontaneous intracerebral hemorrhage. However, the association between blood calcium levels and bleeding extent in heart valve replacement patients has not been clearly established. This study aimed at determining the association between blood calcium levels and perioperative hemorrhage after heart valve replacement therapy. Methods: Based on preoperative blood calcium levels, patients were grouped into the hypocalcemia group and normocalcemia group. Postoperative bleeding, blood product use, and complications were monitored during hospitalization. The association between blood calcium levels and major bleeding was determined by multivariable logistic regression models. Results: In the first 12 h after surgery, bleeding in hypocalcemia group was significantly larger than that of the normocalcemia group (338 ± 234 mL vs 232 ± 96 mL; p =.024). The outcome was the same when the overall chest tube output was considered (950 ± 447 mL vs 738 ± 220 mL; p =.038). The incidence of major bleeding was 65.91% in the hypocalcemia group and 18.97% in the normocalcemia group (p =.001). Postoperative complications in the two groups were similar. After adjusting for multiple covariates, the adjusted odds ratios (OR) for participants in hypocalcemia group was 10.01 (95% CI 3.35–34.82), compared with that in normocalcemia group (p <.001). Conclusion: In patients undergoing heart valve surgery, preoperative blood concentrations of calcium are associated with postoperative blood loss. Hypocalcemia before operation may increase the risk of postoperative bleeding. When patients with valvular heart disease present with hypocalcemia before surgery, prompt intervention may lead to better control of postoperative bleeding. [ABSTRACT FROM AUTHOR]

When high thromboembolic and bleeding risks coexist, the former tends to influence physicians' decision making for anti-coagulation therapy. However, the ideal is to weigh the risk of major bleeding and stroke together to ensure effective anti-coagulation treatment, which is a limitation of traditional guideline recommended CHA2DS2-VASc and HAS-BLED. This meta-analysis assesses the performance of the two new scores — ABC and GARFIELD-AF compared to CHA2DS2-VASc and HAS-BLED for major bleeding and stroke outcomes in patients with atrial fibrillation (AF) on anticoagulation therapy. MEDLINE and Cochrane central were searched from 2010 to February 2023 that compared GARFIELD-AF and/or ABC with CHA2DS2-VASc and/or HAS-BLED scores using C-statistics to assess their discriminative ability. 12 studies were included in this meta-analysis. When assessing stroke risk prediction, GARFIELD-AF stroke (C-Statistic: 0.71; 95 % CI: 0.70–0.72; I2 = 0 %, p < 0.05) was found to be significantly better than ABC-stroke (C-Statistic: 0.67; 95 % CI: 0.65–0.68; I2 = 0 %, p < 0.05), and CHA2DS2-VASc (C-Statistic: 0.64; 95 % CI: 0.60–0.67; I2 = 92 %, p < 0.05). Additionally, when assessing bleeding risk prediction, ABC-bleeding (C-Statistic: 0.66; 95 % CI: 0.61–0.70; I2 = 84 %, p < 0.05), GARFIELD-AF (C-Statistic: 0.64; 95 % CI: 0.60–0.68; I2 = 95 %, p < 0.05), and HAS-BLED (C-Statistic: 0.64; 95 % CI: 0.62–0.66; I2 = 85 %, p < 0.05) all showed equivalent performances. The GARFIELD-AF stroke score showed superior performance to the well-established CHA2DS2-VASc score as well as the ABC-stroke score. Therefore, new guidelines should favor GARFIELD-AF use in clinical practice. [ABSTRACT FROM AUTHOR]

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

Introduction: Oral anticoagulant therapy comes at the cost of a significant bleeding risk. However, it is hard to predict which patients are at risk of major bleeding. Previously we found associations of Calibrated Automated Thrombinography (CAT) parameters obtained in the presence of TIX-5 (an inhibitor of the FV activation by FXa), and plasma levels of TFPIα, γ’-fibrinogen and soluble thrombomodulin with major bleeding in the BLEEDS cohort, a cohort especially powered to find new biomarkers of major bleeding during VKA therapy. Methods: To determine and compare the predictive capability for major bleeding in the BLEEDS cohort of the above biomarkers, also in a combined model with clinical risk factors, we performed Univariable Prentice-weighted Cox regression analyses and Bayesian variable selection. Results: The highest predictive value among the laboratory measures were found for thrombin generation lagtime in the presence of TIX-5 (TIX-5 lagtime per 25% increase, hazard ratio (HR) 1.11, 95%CI 1.04–1.18, p=0.001) and full-length tissue factor pathway inhibitor (TFPIα) (per 25% increase HR 1.12, 95%CI 1.03–1.21, p=0.008), which remained significant after correction for multiple testing, and independently associated with major bleeding after Bayesian variable selection. Only the addition of TIX-5 lagtime to the clinical risk factors improved prediction of major bleeding significantly (p

This umbrella review synthesizes data from 17 meta-analyses investigating the comparative outcomes of catheter ablation (CA) and medical treatment (MT) for atrial fibrillation (AF). Outcomes assessed were mortality, risk of hospitalization, AF recurrence, cardiovascular events, pulmonary vein stenosis, major bleeding, and changes in left ventricular ejection fraction (LVEF) and MLHFQ score. The findings indicate that CA significantly reduces overall mortality and cardiovascular hospitalization with high strength of evidence. The risk of AF recurrence was notably lower with CA, with moderate strength of evidence. Two associations reported an increased risk of pulmonary vein stenosis and major bleeding with CA, supported by high strength of evidence. Improved LVEF and a positive change in MLHFQ were also associated with CA. Among patients with AF and heart failure, CA appears superior to MT for reducing mortality, improving LVEF, and reducing cardiovascular rehospitalizations. In nonspecific populations, CA reduced mortality and improved LVEF but had higher complication rates. Our findings suggest that CA might offer significant benefits in managing AF, particularly in patients with heart failure. However, the risk of complications, including pulmonary vein stenosis and major bleeding, is notable. Further research in understudied populations may help refine these conclusions. [ABSTRACT FROM AUTHOR]

Background: Real-world evidence on direct oral anticoagulant outcomes among Non-Valvular Atrial Fibrillation (NVAF) patients is limited. We aimed to evaluate stroke/systemic embolism (SE) and major bleeding (MB) risks among NVAF patients continuing or switching to different oral anticoagulants. Methods: Using Optum's de-identified Clinformatics® Data Mart Database, we identified NVAF patients initiating apixaban or rivaroxaban between 1 January 2013 and 31 December 2021. Patients switching therapies within 30 days before or 90 days after discontinuing their initial DOAC and those who continued initial therapy were included. The index date was the switch date for switchers, while continuers were assigned a hypothetic index date. Switchers and continuers were propensity score matched based on pre-index characteristics. Results: Among 167,868 apixaban and 65,888 rivaroxaban initiators, 2900 apixaban-to-rivaroxaban switchers were matched with 14,500 apixaban continuers, and 2873 rivaroxaban-to-apixaban switchers were matched with 14,365 rivaroxaban continuers. Apixaban-to-rivaroxaban switching was associated with higher stroke/SE risk (HR: 1.99, 95% CI: 1.38–2.88) and MB risk (HR:1.80, 95% CI: 1.46–2.23) than continuing apixaban. Rivaroxaban-to-apixaban switching had similar stroke/SE risk (HR: 0.74, 95% CI: 0.45–1.22) but lower MB risk (HR: 0.49, 95% CI: 0.38–0.65) than continuing rivaroxaban. Conclusions: These findings may aid physicians and patients in making informed decisions when considering a switch between apixaban and rivaroxaban. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is an irregular heart rhythm which is becoming more and more common in this new era. Obesity is a risk factor for cardiovascular events, and obese patients are more at risk for stroke. The Framingham Heart Study demonstrated an increase in the developmental risk of AF by 4% for every unit (kg/m2) increase in body mass index (BMI). An anticoagulant is often required for the management of such patients. In this analysis, we aimed to systematically compare the clinical outcomes which were associated with rivaroxaban versus warfarin for the treatment of obese patients with non-valvular AF. Methods: PubMed, EMBASE, Web of Science, http://www.ClinicalTrials.gov, Google Scholar, and Cochrane Central were the searched databases. Clinical outcomes including stroke, systemic embolism, and major bleeding were the endpoints. In this study, dichotomous data were analyzed by the RevMan software version 5.4. Risk ratio (RR) with 95% confidence interval (CI) was used for result interpretation. Results: Ten studies consisting of a total number of 168,081 obese participants were included whereby 81,332 participants were treated with rivaroxaban and 86,749 participants were treated with warfarin. The risks of ischemic (RR: 0.79, 95% CI: 0.74–0.84; P = 0.00001) and hemorrhagic stroke (RR: 0.61, 95% CI: 0.48–0.76; P = 0.0001) as well as systemic embolism (RR: 0.73, 95% CI: 0.62–0.87; P = 0.0004) were significantly lower with rivaroxaban compared to warfarin for the management of these obese patients with non-valvular AF. Rivaroxaban was also associated with a significantly lower risk of major bleeding (RR: 0.75, 95% CI: 0.65–0.87; P = 0.0001). Conclusion: Based on this analysis, rivaroxaban seemed to be a better option in comparison to warfarin, due to its association with significantly lower risks of stroke and bleeding outcomes in obese patients with non-valvular AF. However, this hypothesis should further be confirmed in larger clinical trials. [ABSTRACT FROM AUTHOR]

Background and aims: Liver diseases play an important role in the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB-4) index is a non-invasive score recommended for detecting liver fibrosis. Since the association between liver fibrosis and outcomes of AF patients is still not well defined, we aim to analyze prognosis impact of FIB-4 index in those patients. Methods: A retrospective population-based cohort study was performed with 12,870 unselected patients from a single health area in Spain with AF from 2014 to 2019. Cox regression models were used to estimate the association of FIB-4 index with mortality. The association with ischemic stroke (IS), major bleeding (MB), acute myocardial infarction (AMI), and heart failure (HF) was assessed by competing risk analysis. Results: A total of 61.1%, 22.0%, and 16.9% were classified as low, moderate and high risk of liver fibrosis according to FIB-4 index, respectively. During a mean follow-up of 4.5 ± 1.7 years, FIB-4 index was associated with mortality (adjusted HR 1.04; 95% CI 1.01–1.06; p = 0.002), MB and HF (adjusted sHR 1.03, 95% CI 1.01–1.04; p = 0.004), but not with IS or with AMI. The association between FIB-4 and MB was only found in patients treated with vitamin K antagonists, not in patients on direct oral anticoagulants. Conclusions: The FIB-4 index, a non-invasive scoring method for evaluating liver fibrosis, is independently associated with all-cause mortality, MB and HF in patients with AF, suggesting that it may be useful as a risk assessment tool to identify adverse outcomes in patients with AF. [ABSTRACT FROM AUTHOR]

• During the first 14 days of Direct oral anticoagulant (DOAC) therapy, a slight increase in serum levels of tacrolimus and cyclosporine can be found; • Serum Levels and concentration/dose ratio of Tacrolimus and cyclosporin were stable at 18 months follow-up in patients treated with DOAC; • DOACS have a similar safety and efficacy profile when compared to antagonist of vitamin K and no difference in terms of bleeding, thromboembolic events and renal function decline was found. direct oral anticoagulants (DOACs) are an alternative to conventional antagonist of vitamin-K (AVK). However, immune suppressive drugs (ISDs) may interfere with DOACs pharmacokinetic. evaluate safety and efficacy profile of DOACs compared to AVK in kidney transplant recipients (KTRs) treated with ISDs. a multi-center study from 4 Italian University hospitals enrolling consecutive KTRs on DOACs or AVK was carried out. Sixty-six patients on DOACs were compared with fifty patients on AVK with similar clinical features. Serial evaluation of renal function and serum levels of ISDs during 18 months follow-up (FU) was performed. Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73m2. ISDs included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p=0.80) and cyclosporine (+0.12±0.25 p=0.94) not statistically significant. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or AVK and no differences in term of major bleeding (6% vs 4% p=0.69), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs vs AVK therapy (-3.9±1 vs -3.8±2 p=0.82). DOACs have similar safety and efficacy than AVK among KTRs treated with ISDs. However, careful evaluation of potential drug interaction and ISDs serum levels is needed. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under‐represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years. Methods: We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE. Results: From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep‐vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths). Conclusions: In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population. [ABSTRACT FROM AUTHOR]

Introduction: Aortic stenosis is the most common valvular heart disease requiring surgical treatment. Minimally invasive surgical techniques have emerged as alternatives to traditional median sternotomy. Objective: To analyze the possible risk factors associated with major bleeding in patients undergoing aortic valve replacement via right anterior mini-thoracotomy and to share the results found in our center. Materials and methods: A retrospective, observational, longitudinal study was conducted in patients undergoing right anterior mini-thoracotomy from July 2015 to December 2022. Demographic and clinical data, as well as relevant surgical and echocardiographic variables, were collected. Results: The mean age of the study population had a mean age of 58 years, with a predominance of men under 65 years of age. Only three patients experienced major bleeding 4.47%. Advanced age and extracorporeal circulation time (minutes) were associated with bleeding. No significant differences were found in other variables analyzed. Conclusions: The study results indicate a low rate of postoperative bleeding in minimally invasive surgery. Advanced age and prolonged extracorporeal circulation time were identified as significant risk factors for major bleeding. However, further studies with a larger sample size are needed to better understand these factors and the safety of minimally invasive surgery. [ABSTRACT FROM AUTHOR]

(1) Background: The clinical management of anticoagulated patients treated with direct oral anticoagulants (DOAC) or Vitamin K antagonists (VKA) needing emergency surgery is challenging. (2) Methods: The prospective German RADOA registry investigated treatment strategies in DOAC- or VKA-treated patients needing emergency surgery within 24 h after admission. Effectiveness was analysed by clinical endpoints including major bleeding. Primary observation endpoint was in hospital mortality until 30 days after admission. (3) Results: A total of 78 patients were included (DOAC: 44; VKA: 34). Median age was 76 years. Overall, 43% of the DOAC patients and 79% of the VKA patients were treated with prothrombin complex concentrates (PCC) (p = 0.002). Out of the DOAC patients, 30% received no hemostatic treatment compared to 3% (1/34) of the VKA patients (p = 0.002), and 7% of the DOAC patients and 21% of the VKA patients developed major or clinically relevant non-major bleeding at the surgical site (p = 0.093). In-hospital mortality was 13% with no significant difference between the two treatment groups (DOAC: 11%, VKA: 15%; p > 0.20). (4) Conclusions: The 30-day in-hospital mortality rate was comparable between both patient groups. VKA patients required significantly more hemostatic agents than DOAC patients in the peri- and postoperative surgery period. [ABSTRACT FROM AUTHOR]

BACKGROUND: The traditional definition of massive transfusion is 10 red blood cell units transfused within 24 hr. This definition has been faulted for excluding patients who die early from exsanguination. Alternative major bleeding definitions in the trauma literature include time-based (e.g., Resuscitation Intensity) and event based (e.g., Sharpe) transfusion thresholds. OBJECTIVE: The study objective was to compare four definitions of major bleeding, including a modification to the Sharpe definition, on clinically relevant processes and outcomes. METHODS: This is a retrospective cohort study of adult trauma patients admitted from the field to a Level I trauma center from 2014 to 2019. Data sources were the trauma registry, blood bank, and electronic medical records. Transfusion thresholds were defined as follows: Resuscitation Intensity--4 units of any combination of crystalloids, colloids, or blood products within the first 30 min of arrival; Sharpe--10 red blood cell units from trauma bay presentation to inpatient admission (a proxy for the interval of hemorrhage control); Modified Sharpe--10 units of any combination of blood products during the same interval. The study analysis consisted of descriptive statistics. RESULTS: The cohort contained 187 subjects. Of 39 deaths, 28 (72%) occurred within 6 hr following arrival. Modified Sharpe captured 27 (96%) of these 28 subjects, whereas Resuscitation Intensity captured 20 (71%). Sharpe and the traditional definition each captured 22 subjects (79%). Modified Sharpe captured 17%-25% of deaths missed by the other definitions. CONCLUSION: Modified Sharpe may optimally indicate major bleeding during trauma resuscitation. [ABSTRACT FROM AUTHOR]

Purpose: Oral anticoagulants effectively prevent stroke/systemic embolism among patients with non-valvular atrial fibrillation but remain under-prescribed. This study evaluated temporal trends in oral anticoagulant use, the incidence of stroke/systemic embolism and major bleeding, and economic outcomes among elderly patients with non-valvular atrial fibrillation and CHA2DS2–VASc scores ≥ 2. Methods: Retrospective analyses were conducted on Medicare claims data from January 1, 2012 through December 31, 2017. Non-valvular atrial fibrillation patients aged ≥ 65 years with CHA2DS2–VASc scores ≥ 2 were stratified by calendar year (2013–2016) of care to create calendar-year cohorts. Patient characteristics were evaluated across all cohorts during the baseline period (12 months before diagnosis). Treatment patterns and clinical and economic outcomes were evaluated during the follow-up period (from diagnosis through 12 months). Results: Baseline patient characteristics remained generally similar between 2013 and 2016. Although lack of oral anticoagulant prescriptions among eligible patients remained relatively high, utilization did increase progressively (53–58%). Among treated patients, there was a progressive decrease in warfarin use (79–52%) and a progressive increase in overall direct oral anticoagulant use (21–48%). There were progressive decreases in the incidence of stroke/systemic embolism 1.9–1.4 events per 100 person years) and major bleeding (4.6–3.3 events per 100 person years) as well as all-cause costs between 2013 and 2016. Conclusions: The proportions of patients with non-valvular atrial fibrillation who were not prescribed an oral anticoagulant decreased but remained high. We observed an increase in direct oral anticoagulant use that coincided with decreased incidence of clinical outcomes as well as decreasing total healthcare costs. [ABSTRACT FROM AUTHOR]

Introduction: Venous thromboembolism (VTE) consists of deep vein thrombosis (DVT) and pulmonary embolism (PE). Rivaroxaban is a direct oral anticoagulant (DOAC) inhibiting activated coagulation factor X (FXa), and exerts several advantages in the treatment of VTE compared to conventional therapy. However, the efficacy and safety of rivaroxaban in elderly patients with VTE was still poorly understood. Methods: The study was carried out using an observational and non-interventional approach. A total of 576 patients aged ≥ 60 years with newly diagnosed VTE were included in the study. All patients received rivaroxaban with recommended treatment duration of ≥ 3 months for secondary prevention. In addition, 535 elderly patients with various diseases except VTE were included in the study in a retrospective and randomized way. Results: The total bleeding rate was 12.2% (70/576). Major bleeding and non-major clinically relevant (NMCR) bleeding occurred in 4 (0.69%) patients and 5 (0.87%) patients, respectively. The rate of recurrent VTE was 5.4%. The mean level of D-dimers was increased by 467.2% in the elderly patients with VTE compared with the elderly patients without VTE. The elderly patients with VTE receiving rivaroxaban at a dose of 10 mg once daily (n = 134) had lower risk for bleeding (3.7% vs 14.7%; P = 0.001) and a similar rate of recurrent VTE (4.5% vs 5.7%; P = 0.596) as compared to the elderly patients with VTE receiving rivaroxaban at higher doses including 15 mg once daily and 20 mg once daily (n = 442). In addition, age, concomitant aspirin, hemoglobin, activated partial thromboplastin time (APTT), and rivaroxaban doses were independent predictive factors for bleeding events. Conclusions: The study suggested that a dose of 10 mg once daily should be the priority in elderly patients with VTE receiving long-term rivaroxaban anticoagulation therapy in view of reduced bleeding risk. [ABSTRACT FROM AUTHOR]

Background: Little is known about anticoagulation medication nonadherence patterns impacting effectiveness and safety outcomes in clinical practice. Objective: We identified adherence trajectories of extended therapy with direct-acting oral anticoagulants (DOACs) and warfarin after 6 months initial anticoagulant therapy among Medicare beneficiaries with venous thromboembolism (VTE). We further assessed the associated recurrent VTE and major bleeding risks. Methods: Using group-based trajectory models, this retrospective cohort study identified distinct beneficiary subgroups with similar adherence patterns of extended-phase anticoagulant treatment (DOACs or warfarin) for patients with VTE who completed 6 months of initial anticoagulant treatment. We examined associations between adherence trajectories and risks of recurrent VTE and major bleeding using inverse probability treatment weighted Cox proportional hazards models. Results: Compared with no extended treatment, consistently high DOAC adherence was associated with decreased recurrent VTE risk (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.21-0.51) without increased major bleeding risk, and consistently high warfarin adherence was associated with decreased recurrent VTE risk (HR = 0.62, 95% CI = 0.40-0.95) and increased major bleeding risk (HR = 1.64, 95% CI = 1.12-2.41). Gradually declining adherence to DOACs (HR = 1.80, 95% CI = 1.07-3.03) or warfarin (HR = 2.34, 95% CI = 1.57-3.47) was associated with increased bleeding risk with no change in recurrent VTE risk. Conclusion and relevance: This real-world evidence suggests persistently adhering to extended DOAC therapy is associated with lower recurrent VTE risk without increasing major bleeding among Medicare beneficiaries with VTE. Persistently adhering to extended warfarin therapy was associated with lower recurrent VTE risk but higher major bleeding risk. [ABSTRACT FROM AUTHOR]

Aim: Fondaparinux is a synthetic anticoagulant that inhibits thrombosis by suppressing factor Xa. The efficacy of fondaparinux for orthopedic surgeries has been revealed by several foreign studies; however, relevant evidence in Chinese patients is lacking. This study intended to investigate the occurrence rate and risk factors of in-hospital venous thromboembolism (VTE), major bleeding, and death in patients receiving fondaparinux after orthopedic surgery or trauma surgery. Methods: Totally, 1258 patients who received fondaparinux after orthopedic surgery or trauma surgery were retrospectively enrolled. Meanwhile, in-hospital VTE, major bleeding, and death were obtained for assessment. Besides, adverse events were recorded. Results: The occurrence rates of in-hospital VTE, major bleeding, and death were 2.5%, 21.8%, and 0.0%, respectively. The multivariate logistic regression analysis revealed that only age (> 60 years vs. ≤ 60 years) (odd ratios (OR) = 3.380, P = 0.013) was independently correlated with increased risk of in-hospital VTE. Additionally, osteoarthritis diagnosis (OR = 3.826, P < 0.001), femoral head necrosis diagnosis (OR = 1.809, P = 0.034), hip replacement (vs. internal fracture fixation) (OR = 2.199, P = 0.007), knee replacement (vs. internal fracture fixation) (OR = 2.781, P = 0.002), and serum creatinine (abnormal vs. normal) (OR = 1.677, P = 0.012) were independently linked to a higher risk of in-hospital major bleeding. Moreover, the common adverse events included pain (56.6%), wound bleeding (23.0%), increased drainage (5.2%), etc. Conclusion: Fondaparinux realizes low occurrence rates of in-hospital VTE and major bleeding with tolerable adverse events in patients receiving orthopedic surgery or trauma surgery. [ABSTRACT FROM AUTHOR]

More than 1 million transcatheter-based cardiovascular procedures across the spectrum of interventional cardiology are performed annually in the United States. With the expanded indications for and increased complexities associated with these procedures, interventional cardiologists are expected to possess the requisite expertise to complete these interventions safely and effectively. While the art of vascular access and closure remains a prerequisite and critical skillset in contemporary practice, there remain significant variations in the techniques employed, resulting in the bleeding and vascular complications encountered in clinical practice. With an increasing recognition of the potential merits to standardized approaches to vascular access and closure, cardiovascular societies have put forth recommendations around best practices for performing these procedures in the cardiac catheterization laboratories. In this review, we aim to: (1) Examine the evolving definitions of bleeding and vascular complications; (2) Review best practices for transradial and transfemoral access and closure, including for large bore procedures; and (3) Highlight knowledge gaps and proposed areas of clinical research pertaining to vascular access which may inform clinical practice and potentially optimize the outcomes of patients undergoing transcatheter-based cardiac and vascular interventions.

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.

Abstract Background The real‐world outcomes of edoxaban treatment in patients with atrial fibrillation (AF) were analyzed in the ETNA‐AF (Edoxaban Treatment in Routine Clinical Practice) study involving data from multiple regional registries. This report addresses effectiveness and safety of edoxaban in the Korean ETNA‐AF population. Methods One‐year data from 1887 Korean ETNA‐AF participants were analyzed according to edoxaban dose and patient age and compared with results of other ETNA‐AF registries. Results Approximately 70% of patients received the recommended doses of edoxaban (60 mg/30 mg); non‐recommended 60 mg and 30 mg doses were prescribed to 9.6% and 19.8% of the patients, respectively. The proportions of reference age (