Clinical outcomes of patients with atrial fibrillation in relation to multimorbidity status changes over time and the impact of ABC pathway compliance: a nationwide cohort study.

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.

Patients with atrial fibrillation and common exclusion criteria from clinical trials are at high risk of clinical events: the Murcia AF Project II (MAFP-II) cohort study.

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.

Antiplatelet Effect of Low-Dose Prasugrel in Elderly Patients Undergoing Percutaneous Coronary Interventions.

BACKGROUND: Low-dose prasugrel (5 mg) has been proposed for patients with Acute Coronary Syndrome (ACS) and advanced age or low body weight. However, the routine use of dose-adjusted prasugrel in this high-risk subset of patients is still debated. AIM: This study aimed to assess the prevalence and predictors of HRPR among elderly patients treated with low-dose (5 mg) prasugrel to evaluate the routine use of dose-adjusted prasugrel in this high-risk subset of patients. METHODS: We included 59 elderly patients (≥75 years) treated with Dual Antiplatelet Therapy (DAPT: acetylsalicylic acid (ASA) 100-160 mg + prasugrel 5 mg) after Percutaneous Coronary Interventions (PCI) and undergoing platelet function assessment (by whole blood impedance aggregometry) 30-90 days post-discharge. RESULTS: At a median follow-up of 43 days (interquartile range-IQR: 32-54), high-on treatment residual platelet reactivity (HRPR) occurred in 25 patients (42.4%), who displayed a greater body mass index (BMI) (p=0.02), lower levels of vitamin D (p=0.05) and were more frequently treated with nitrates (p=0.03). After multivariate analysis, BMI was the only independent predictor of prasugrel HRPR, and a BMI >26 was the best cut-off for predicting HRPR (adjusted Odds Ratio - OR=8.6, 95%CI: 2.2-33.9, p=0.002). CONCLUSION: Among elderly patients receiving DAPT after PCI, HRPR is common with low-dose prasugrel. A greater BMI, especially for values ≥26, is the only independent predictor of HRPR with prasugrel 5 mg.

Ultrasound-Facilitated, Catheter-Directed Thrombolysis for Acute Pulmonary Embolism.

BACKGROUND: Acute pulmonary embolism (APE) poses a significant risk to patient health, with treatment options varying in efficacy and safety. Ultrasound-facilitated catheter-directed thrombolysis (USCDT) has emerged as a potential alternative to conventional catheter-directed thrombolysis (CDT) for patients with intermediate to high-risk APE. This study aimed to compare the efficacy and safety of USCDT versus conventional CDT in patients with intermediate to high-risk APE. METHODS: This observational retrospective study was conducted at the Armed Forces Hospital, Al-Hada, Taif, the Kingdom of Saudi Arabia (KSA), on 135 patients diagnosed with APE and treated with either USCDT or CDT (58 underwent CDT, while 77 underwent USCDT). The primary efficacy outcome was the change in the right ventricle to the left ventricle (RV/LV) diameter ratio. Secondary outcomes included changes in pulmonary artery systolic pressure and the Miller angiographic obstruction index score. Safety outcomes focused on major bleeding events. RESULTS: Both USCDT and CDT significantly reduced RV/LV diameter ratio (from 1.35 ± 0.14 to 1.05 ± 0.17, P < 0.001) and systolic pulmonary artery pressure (SPAP) (from 55 ± 7 mmHg to 38 ± 7 mmHg, P < 0.001) at 48- and 12-hours post-procedure, respectively, with no significant differences between treatments. However, USCDT was associated with a significantly lower rate of major bleeding events compared to CDT (0% vs. 3.4%, P = 0.008). Multivariate logistic regression analysis revealed that USCDT was associated with a 71.9% risk reduction of bleeding (OR = 0.281, 95% CI = 0.126 - 0.627, P = 0.002). CONCLUSIONS: USCDT is a safe and effective alternative to CDT for the treatment of intermediate to high-risk APE, as it significantly reduces the risk of major bleeding.

Andexanet alfa versus PCC products for factor Xa inhibitor bleeding: A systematic review with meta-analysis.

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.

A Novel Risk Score for Major Bleeding in Japanese Patients with Non-Valvular Atrial Fibrillation: The J-RISK AF Study.

AIM: Oral anticoagulants (OACs) reduce the risk of ischemic stroke but may increase the risk of major bleeding in patients with non-valvular atrial fibrillation (NVAF). Various risk scores, such as HAS-BLED, ATRIA, ORBIT, and DOAC, have been proposed to assess the risk of major bleeding in patients with NVAF receiving OACs. However, limited data are available regarding bleeding risk stratification in Japanese patients with NVAF. METHODS: Of the 16,098 NVAF patients from the J-RISK AF study, the combined data of the five major AF registries in Japan (J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry), we analyzed 11,539 patients receiving OACs (median age, 71 years old; women, 29.6%; median CHA2DS2-VASc score, 3). RESULTS: During the 2-year follow-up period, major bleeding occurred in 274 patients (1.3% per patient-year). In a multivariate Cox proportional hazards analysis, an advanced age, hypertension (systolic blood pressure ≥ 150 mmHg), bleeding history, anemia, thrombocytopenia, and concomitant antiplatelet agents were significantly associated with a higher incidence of major bleeding. We developed a novel risk stratification system, HED-[EPA]2-B3 score, which had a better predictive performance for major bleeding (C-statistics 0.67, [95% confidence interval, 0.63-0.70]) than the HAS-BLED (0.64, [0.60-0.67], P for difference 0.02) and ATRIA (0.63, [0.60-0.66], P for difference ＜0.01) scores. Furthermore, it was non-significantly higher than the ORBIT (0.65, [0.62-0.68], P for difference 0.07) and DOAC (0.65, [0.62-0.68], P for difference 0.17) scores. CONCLUSION: Our novel risk stratification system, the HED-[EPA]2-B3 score, may be useful for identifying Japanese patients receiving OACs at a risk of major bleeding.

Comparison of rivaroxaban and low molecular weight heparin in the treatment of cancer-associated venous thromboembolism: a Swedish national population-based register study.

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).

Τakotsubo Syndrome After Surgical Removal of the Thyroid Gland and Major Bleeding.

A 58-year-old male with a medical history of arterial hypertension, dyslipidemia, and psoriasis was admitted for a scheduled surgical removal of the thyroid gland. During the surgery, the patient suffered severe blood loss caused by vascular complications. After the operation, his electrocardiogram showed diffuse ST segment elevation along with high-sensitivity cardiac troponin T elevation and severe left ventricular systolic dysfunction. An emergency coronary angiography showed unobstructed coronary arteries. However, the left ventriculography demonstrated akinesia of the apical segments and hyperkinesia of the basal segments during systole. The patient was diagnosed with Takotsubo syndrome and he was successfully stabilized over the course of the next few days. Takotsubo cardiomyopathy is characterized by transient left ventricular systolic dysfunction and although the clinical and electrocardiographical presentation is similar to an acute coronary syndrome, the coronary arteries are unobstructed. Stressful events, both physical or psychological, could trigger an excessive catecholaminergic response which can cause the syndrome. Repetitive echocardiograms in our patient demonstrated complete recovery of the systolic function after a few days.

ANMCO/SIMEU consensus document on the use of reversal agents for antithrombotic therapies in patients with ongoing bleeding or at high risk of haemorrhagic events.

In recent decades, an incredible evolution in antithrombotic therapies used for treating patients with atherosclerosis, atrial fibrillation, and venous thromboembolism has been observed, leading to the availability of increasingly safe drugs. Nonetheless, bleeding complications remain a significant concern, with considerable health, social, and economic implications. To improve the acute management of patients experiencing or at risk for major bleeding events, specific reversal agents for antithrombotic drugs have been recently developed. While these agents demonstrate effectiveness in small-scale pharmacodynamic studies and clinical trials, it is imperative to balance the benefits of reversing antiplatelet or anticoagulant therapy against the risk of prothrombotic effects. These risks include the potential loss of antithrombotic protection and the prothrombotic tendencies associated with bleeding, major surgery, or trauma. This joint document of the Italian Association of Hospital Cardiologists (Associazione Nazionale Medici Cardiologi Ospedalieri) and the Italian Society of Emergency Medicine (Società Italiana di Medicina d'Emergenza-Urgenza) delineates the key features and efficacy of available reversal agents. It also provides practical flowcharts to guide their use in patients with active bleeding or those at elevated risk of major bleeding events.

Relation of changes in ABC pathway compliance status to clinical outcomes in patients with atrial fibrillation: A report from the COOL-AF registry.

AIM: The Atrial fibrillation Better Care (ABC) pathway provides a framework for holistic care management of atrial fibrillation (AF) patients. This study aimed to determine the impact of changes in compliance to ABC pathway management on clinical outcomes. METHODS: This is a prospective multicenter AF registry. Patients with non-valvular AF were enrolled and follow-up for 3 years. Baseline and follow-up compliance to the ABC pathway was assessed. The main outcomes were all-cause death, ischemic stroke/systemic embolism (SSE), major bleeding, and heart failure. RESULTS: There studied 3096 patients (mean age 67.6 ± 11.1 years, 41.8% female). Patients were categorized into 4 groups: Group 1: ABC compliant at baseline and 1 year [n = 1022 (33.0%)]; Group 2: ABC non-compliant at baseline but compliant at 1 year [n = 307 (9.9%)]; Group 3: ABC compliant at baseline and non-compliant at 1 year [n = 312 (10.1%)]; and Group 4: ABC non-compliant at baseline and also at 1 year [n = 1455 (47.0%)]. The incidence rates (95% confidence intervals, CI) of the composite outcome for Group 1 to 4 were 5.56 (4.54-6.74), 7.42 (5.35-10.03), 9.74 (7.31-12.70), and 11.57 (10.28-12.97), respectively. With Group 1 as a reference, Group 2-4 had hazard ratios (95% CI) of the composite outcome of 1.32 (0.92-1.89), 1.75 (1.26-2.43), and 2.07 (1.65-2.59), respectively. CONCLUSION: Re-evaluation of compliance status of the ABC pathway management is needed to optimize integrated care management and improve clinical outcomes. AF patients who were ABC pathway compliant at baseline and also at follow-up had the best clinical outcomes.

Predicting multifaceted risks using machine learning in atrial fibrillation: insights from GLORIA-AF study.

Aims: Patients with atrial fibrillation (AF) have a higher risk of ischaemic stroke and death. While anticoagulants are effective at reducing these risks, they increase the risk of bleeding. Current clinical risk scores only perform modestly in predicting adverse outcomes, especially for the outcome of death. We aimed to test the multi-label gradient boosting decision tree (ML-GBDT) model in predicting risks for adverse outcomes in a prospective global AF registry. Methods and results: We studied patients from phase II/III of the Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation registry between 2011 and 2020. The outcomes were all-cause death, ischaemic stroke, and major bleeding within 1 year following the AF. We trained the ML-GBDT model and compared its discrimination with the clinical scores in predicting patient outcomes. A total of 25 656 patients were included [mean age 70.3 years (SD 10.3); 44.8% female]. Within 1 year after AF, ischaemic stroke occurred in 215 (0.8%), major bleeding in 405 (1.6%), and death in 897 (3.5%) patients. Our model achieved an optimized area under the curve in predicting death (0.785, 95% CI: 0.757-0.813) compared with the Charlson Comorbidity Index (0.747, P = 0.007), ischaemic stroke (0.691, 0.626-0.756) compared with CHA2DS2-VASc (0.613, P = 0.028), and major bleeding (0.698, 0.651-0.745) as opposed to HAS-BLED (0.607, P = 0.002), with improvement in net reclassification index (10.0, 12.5, and 23.6%, respectively). Conclusion: The ML-GBDT model outperformed clinical risk scores in predicting the risks in patients with AF. This approach could be used as a single multifaceted holistic tool to optimize patient risk assessment and mitigate adverse outcomes when managing AF.

Evidence of the association between increased use of direct oral anticoagulants and a reduction in the rate of atrial fibrillation-related stroke and major bleeding at the population level (2012–2019) / Evidencia a nivel poblacional de la asociación entre el aumento del uso de anticoagulantes orales directos y una reducción de la incidencia de ictus y hemorragias mayores relacionados con fibrilación auricular (2012-2019)

Background: The introduction of direct-acting oral anticoagulants (DOACs) has shown to decrease atrial fibrillation (AF)-related stroke and bleeding rates in clinical studies, but there is no certain evidence about their effects at the population level. Our aim was to assess changes in AF-related stroke and major bleeding rates between 2012 and 2019 in Andalusia (Spain), and the association between DOACs use and events rates at the population level. Methods: All patients with an AF diagnosis from 2012 to 2019 were identified using the Andalusian Health Population Base, that provides clinical information on all Andalusian people. Annual ischemic and hemorrhagic stroke, major bleeding rates, and used antithrombotic treatments were determined. Marginal hazard ratios (HR) were calculated for each treatment. Results: A total of 95,085 patients with an AF diagnosis were identified. Mean age was 76.1±10.2 years (49.7% women). An increase in the use of DOACs was observed throughout the study period in both males and females (p<0.001). The annual rate of ischemic stroke decreased by one third, while that of hemorrhagic stroke and major bleeding decreased 2–3-fold from 2012 to 2019. Marginal HR was lower than 0.50 for DOACs compared to VKA for all ischemic or hemorrhagic events. Conclusions: In this contemporary population-based study using clinical and administrative databases in Andalusia, a significant reduction in the incidence of AF-related ischemic and hemorrhagic stroke and major bleeding was observed between 2012 and 2019. The increased use of DOACs seems to be associated with this reduction.(AU)

Introducción: La introducción de los anticoagulantes orales de acción directa (ACOD) ha demostrado disminuir las tasas de accidentes cerebrovasculares y hemorragias relacionados con fibrilación auricular (FA) en estudios clínicos, pero no hay tanta evidencia sobre sus efectos a nivel poblacional. Nuestro objetivo fue evaluar los cambios en la incidencia de ictus y hemorragias mayores relacionados con FA entre 2012 y 2019 en Andalucía (España), y estudiar la asociación entre el uso de ACOD y estos eventos a nivel poblacional. Métodos: Se incluyeron pacientes con diagnóstico de FA entre los años 2012 y 2019 en la Base de Población Sanitaria de Andalucía, que proporciona información clínica de todos los andaluces. Se determinaron los accidentes cerebrovasculares isquémicos y hemorrágicos anuales, las tasas de sangrado mayor y los tratamientos antitrombóticos utilizados. Se estimaron los hazard ratio para cada tratamiento. Resultados: Se identificaron un total de 95.085 pacientes con diagnóstico de FA. La edad media fue de 76,1±10,2 años (49,7% mujeres). Se observó un aumento en el uso de ACOD a lo largo del período de estudio, tanto en varones como en mujeres (p<0,001). La tasa anual de ictus isquémico disminuyó en un tercio, mientras que la de ictus hemorrágico y hemorragia mayor se redujo de 2 a 3 veces entre 2012 y 2019. Los hazard ratio fueron inferiores a 0,50 para los ACOD en comparación con los antivitamina K para todos los eventos isquémicos o hemorrágicos. Conclusiones: En este estudio poblacional contemporáneo, se observó, utilizando bases de datos clínicas y administrativas de Andalucía, una reducción significativa en la incidencia de ictus isquémico y hemorrágico, y hemorragia mayor relacionados con FA entre los años 2012 y 2019. El mayor uso de ACOD parece estar asociado con esta reducción.(AU)

Comparison of Outcomes in Patients Requiring Mechanical Circulatory Support Who Received Cangrelor in Addition to Anticoagulation Versus Anticoagulation Alone.

OBJECTIVES: To evaluate the safety of cangrelor administered concurrently with heparin or bivalirudin in patients on mechanical circulatory support. DESIGN: A single-center, retrospective cohort study of adult patients consecutively admitted between January 2016 and October 2020. SETTING: A tertiary medical center. PARTICIPANTS: 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. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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). CONCLUSIONS: 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.

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

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

Best practices for vascular arterial access and closure: a contemporary guide for the cardiac catheterization laboratory.

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.

Definitions of major bleeding for predicting mortality in critically ill adult patients who survived 24 hours while supported with peripheral veno-arterial extracorporeal membrane oxygenation for cardiogenic shock: a comparative historical cohort study.

PURPOSE: The severity of bleeding events is heterogeneously defined during peripheral veno-arterial extracorporeal membrane oxygenation (pVA-ECMO). We studied three bleeding definitions in pVA-ECMO: the Extracorporeal Life Support Organization (ELSO)-serious bleeding, the Bleeding Academic Research Consortium (BARC), and the universal definition of postoperative bleeding (UPDB) classifications. METHODS: We included consecutive adult patients supported by pVA-ECMO for refractory cardiogenic shock admitted to Lille academic hospitals between January 2013 and December 2019. We assessed the association of bleeding definitions with the primary endpoint of 28-day all-cause mortality with the use of multivariate models accounting for time-dependent and competing variables. We compared models' performances using the Harrell's C-Index and the Akaike information criteria. RESULTS: Twenty-eight-day mortality occurred in 128/308 (42%) 308 patients. The ELSO-serious bleeding (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.09 to 2.56) and BARC ≥ type 2 (HR, 1.55; 95% CI, 1.01 to 2.37) were associated with 28-day mortality (Harrell's C-index, 0.69; 95% CI, 0.63 to 0.74 for both). Predictors of ELSO-serious bleeding were postcardiotomy, body mass index, baseline platelets count, fibrinogen, and hemoglobin levels. CONCLUSION: Extracorporeal Life Support Organization-serious bleeding and BARC ≥ type 2 are relevant definitions of major bleeding regarding their association with mortality in critically ill patients who survived the first 24 hr while supported with pVA-ECMO for cardiogenic shock. STUDY REGISTRATION: CERAR (IRB 00010254-2022-050, Paris, France); first submitted on 18 April 2022.

RéSUMé: OBJECTIF: La gravité des événements hémorragiques est définie de manière hétérogène pendant une oxygénation par membrane extracorporelle veino-artérielle périphérique (ECMO-VA périphérique). Nous avons étudié trois définitions du saignement sous ECMO-VA périphérique : les classifications des saignements graves selon l'Extracorporeal Life Support Organization (ELSO), celles du Bleeding Academic Research Consortium (BARC) et la définition universelle du saignement postopératoire (UPDB). MéTHODE: Nous avons inclus des patient·es adultes pris·es en charge de manière consécutive par ECMO-VA périphérique à la suite d'un choc cardiogénique réfractaire et admis·es dans les centres hospitaliers universitaires de Lille entre janvier 2013 et décembre 2019. Nous avons évalué l'association des définitions du saignement avec le critère d'évaluation principal de mortalité toutes causes confondues à 28 jours à l'aide de modèles multivariés tenant compte des variables dépendantes du temps et concurrentes. Nous avons comparé les performances des modèles à l'aide de l'indice C de Harrell et du critère d'information d'Akaike. RéSULTATS: La mortalité à 28 jours est survenue chez 128/308 (42 %) patient·es. Le saignement grave selon l'ELSO (rapport de risque [RR], 1,67; intervalle de confiance [IC] à 95 %, 1,09 à 2,56) et une classification BARC ≥ type 2 (RR, 1,55; IC 95 %, 1,01 à 2,37) étaient associés à une mortalité à 28 jours (indice C de Harrell, 0,69; IC 95 %, 0,63 à 0,74 pour les deux). Les prédicteurs d'hémorragie grave selon l'ELSO étaient la postcardiotomie, l'indice de masse corporelle, la numération plaquettaire initiale, le taux de fibrinogène et les taux d'hémoglobine. CONCLUSION: Les définitions du saignement grave de l'Extracorporeal Life Support Organization et une classification BARC ≥ type 2 sont des définitions pertinentes des saignements majeurs en ce qui touche à leur association avec la mortalité chez les personnes gravement malades qui ont survécu aux premières 24 heures alors qu'elles étaient prises en charge par ECMO-VA périphérique à la suite d'un choc cardiogénique. ENREGISTREMENT DE L'éTUDE: CERAR (IRB 00010254-2022-050, Paris, France); soumis pour la première fois le 18 avril 2022.

Clinical Background and Coronary Artery Lesions Characteristics in Japanese Patients With Acute Coronary Syndrome Suffering Major Bleeding.

Background: Although the clinical factors that predict major bleeding in Western patients with acute coronary syndrome (ACS) are becoming elucidated, they have not been fully investigated, especially coronary lesion characteristics, in a Japanese population. Methods and Results: ACS patients (n=1,840) were divided into a "bleeding group" and a "no-bleeding group," according to whether they had major bleeding during the 2-year follow-up period, to investigate the prognostic effect of bleeding and the predictive factors of bleeding. Among them, patients who underwent primary percutaneous coronary intervention with optical coherence tomography (OCT) guidance (n=958) were examined to identify the effect of coronary lesion characteristics on bleeding. Of the 1,840 enrolled patients, 124 (6.7%) experienced major bleeding during the 2-year follow-up period. Incidence of cardiovascular death during the 2-year follow-up period was significantly higher among patients with major bleeding (26.4% vs. 8.5%, P=0.001). OCT examination showed that disrupted fibrous cap (DFC: 68% vs. 48%, P=0.014) and calcified plaque (63% vs. 42%, P=0.011) were more prevalent in the bleeding group. DFC was a predictor of major bleeding in the multivariate Cox proportional hazards analyses (hazard ratio 2.135 [95% confidence interval 1.070-4.263], P<0.001). Conclusions: ACS patients with major bleeding had poorer cardiac outcomes. Advanced atherosclerosis at the culprit lesion influences the higher incidence of major bleeding in ACS patients.

Clinical Impact of Switching or Continuation of Apixaban or Rivaroxaban among Patients with Non-Valvular Atrial Fibrillation.

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.

A Novel Nomogram for Predicting Warfarin-Related Bleeding: A Retrospective Cohort Study.

Warfarin is a widely used anticoagulant, and bleeding complications are the main reason why patients discontinue the drug. Currently, there is no nomogram model for warfarin-associated bleeding risk. The aim of this study was to develop a risk-prediction nomogram model for warfarin-related major and clinically relevant non-major (CRNM) bleeding. A total of 280 heart disease outpatients taking warfarin were enrolled, 42 of whom experienced major or CRNM bleeding at the one-year follow-up. The Least Absolute Shrinkage and Selection Operator regression model was employed to identify potential predictors. Backward stepwise selection with the Akaike information criterion was used to establish the optimal predictive nomogram model. The receiver operating characteristic (ROC) curve, calibration plot, Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. The nomogram consisted of four predictors: female (OR = 1.85; 95% CI: 0.91-3.94), TIA (OR = 6.47; 95% CI: 1.85-22.7), TTR (OR = 0.99; 95% CI: 0.97-1.00), and anemia (OR = 2.30; 95% CI: 1.06-4.84). The model had acceptable discrimination (area under the ROC curve = 0.68, 95% CI: 0.59-0.78), and was significantly better than the existing nine warfarin-related bleeding prediction scoring systems. The calibration plot and Hosmer-Lemeshow test (χ² = 7.557; P = .478) indicated well-calibrated data in the model. The DCA demonstrated good clinical utility. In this study, we developed a nomogram to predict the risk of warfarin-related major or CRNM bleeding. The model has good performance, allows rapid risk stratification of warfarin users, and provides a basis for personalized treatment.