Direct Oral Anticoagulants Versus Warfarin in Adults with Durable Left Ventricular Assist Devices: A Systematic Review and Meta-Analysis.

INTRODUCTION: The management of anticoagulation in patients with durable left ventricular assist devices (LVADs) is challenging. Traditionally, warfarin has been used, but its limitations have prompted interest in direct oral anticoagulants (DOACs). This meta-analysis aims to evaluate the safety and efficacy of DOACs compared to warfarin in LVAD patients. METHODS: We searched databases for studies comparing DOACs and warfarin in LVAD patients. Primary outcomes were thromboembolic events and major bleeding events. Secondary outcomes were the individual components of the thromboembolic events, minor bleeding events, and all-cause mortality. Random-effects model was used to calculate log risk-ratios (RR) with 95% confidence intervals (CI). RESULTS: Nine studies with a total of 316 LVAD patients (153 on DOACs, 163 on warfarin) were included. Thromboembolic events were similar between the groups (Log RR -0.42, 95% CI: -1.29 to 0.45, P = 0.34). Major bleeding events were significantly fewer in the DOAC group (Log RR -1.05, 95% CI: -1.73 to -0.36, P < 0.01). Minor bleeding events were also less common with DOACs (Log RR -0.77, 95% CI: -1.46 to -0.07, P = 0.03). No significant differences were observed in pump thrombosis, ischemic cerebrovascular accident events, or all-cause mortality. CONCLUSION: DOACs appear to be a safe and effective alternative to warfarin for anticoagulation in LVAD patients, associated with fewer major and minor bleeding events. These findings support the consideration of DOACs in this patient population, though further research is needed to confirm these results and guide clinical practice.

Prediction model for major bleeding in anticoagulated patients with cancer-associated venous thromboembolism using machine learning and natural language processing.

PURPOSE: We developed a predictive model to assess the risk of major bleeding (MB) within 6 months of primary venous thromboembolism (VTE) in cancer patients receiving anticoagulant treatment. We also sought to describe the prevalence and incidence of VTE in cancer patients, and to describe clinical characteristics at baseline and bleeding events during follow-up in patients receiving anticoagulants. METHODS: This observational, retrospective, and multicenter study used natural language processing and machine learning (ML), to analyze unstructured clinical data from electronic health records from nine Spanish hospitals between 2014 and 2018. All adult cancer patients with VTE receiving anticoagulants were included. Both clinically- and ML-driven feature selection was performed to identify MB predictors. Logistic regression (LR), decision tree (DT), and random forest (RF) algorithms were used to train predictive models, which were validated in a hold-out dataset and compared to the previously developed CAT-BLEED score. RESULTS: Of the 2,893,108 cancer patients screened, in-hospital VTE prevalence was 5.8% and the annual incidence ranged from 2.7 to 3.9%. We identified 21,227 patients with active cancer and VTE receiving anticoagulants (53.9% men, median age of 70 years). MB events after VTE diagnosis occurred in 10.9% of patients within the first six months. MB predictors included: hemoglobin, metastasis, age, platelets, leukocytes, and serum creatinine. The LR, DT, and RF models had AUC-ROC (95% confidence interval) values of 0.60 (0.55, 0.65), 0.60 (0.55, 0.65), and 0.61 (0.56, 0.66), respectively. These models outperformed the CAT-BLEED score with values of 0.53 (0.48, 0.59). CONCLUSIONS: Our study shows encouraging results in identifying anticoagulated patients with cancer-associated VTE who are at high risk of MB.

Components of the Atrial fibrillation Better Care pathway for holistic care of patients with atrial fibrillation: a win ratio analysis from the COOL-AF registry.

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.

Antithrombotic Therapy in Patients Undergoing Peripheral Artery Interventions.

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.

MI2AMI-CS: A meta-analysis comparing Impella and IABP outcomes in Acute Myocardial Infarction-related Cardiogenic Shock.

BACKGROUND: Cardiogenic Shock (CS) complicating acute myocardial infarction (AMI) poses a significant mortality risk, suggesting the opportunity to implement effective mechanical circulatory support strategies. The comparative efficacy of Intra-Aortic Balloon Pump (IABP) and Impella in managing CS-AMI remains a subject of investigation. OBJECTIVE: This meta-analysis aims to evaluate the comparative effectiveness of Impella and IABP in managing CS-AMI, exploring mortality and adverse events. METHODS: A systematic search of major databases from inception to November 2023 identified eight studies, comprising 10,628 patients, comparing Impella and IABP in CS-AMI. Retrospective studies (preferably Propensity-matched) and Randomized Clinical Trials (RCTs) were included. RESULTS: Impella use exhibited significantly higher mortality (57% vs. 46%; OR: 1.44, 95% CI: 1.29-1.60; p < 0.001) and major bleeding (30% vs 15%; OR: 2.93, 95% CI: 1.67-5.13; p < 0.001). CONCLUSIONS: In unselected CS-AMI patients, Impella usage is associated with significantly higher mortality and major bleeding.

Milvexian, a novel factor XIa inhibitor for stroke prevention: pharmacokinetic and pharmacodynamic evaluation.

INTRODUCTION: Antiplatelets and oral anticoagulants are commonly used to treat patients with various cardiovascular and cerebrovascular diseases. However, the primary concern for clinicians remains the risk of bleeding, thus necessitating the development of new therapies. Milvexian is a new anticoagulant that inhibits factor XIa, preventing the pathological formation of thrombi without increasing bleeding risk. AREAS COVERED: This drug evaluation examines the pharmacokinetic properties of milvexian and provides information on its pharmacodynamics and clinical efficacy in treating some cerebrovascular conditions. EXPERT OPINION: Milvexian shows a good pharmacokinetic profile with low renal elimination rates, justifying its use in patients with a high degree of renal impairment, and without relevant drug-drug interactions. In patients affected by acute non-cardioembolic ischemic stroke or high-risk transient ischemic stroke, milvexian, in addition to dual antiplatelet therapy, seems to have a positive efficacy profile without any safety concerns, especially in terms of intracranial hemorrhage. Two phase 3 trials are ongoing to investigate the efficacy and safety of milvexian for preventing cardioembolic and non-cardioembolic ischemic stroke.

Validation of a Major and Clinically Relevant Nonmajor Bleeding Phenotyping Algorithm on Electronic Health Records.

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.

Inpatient outcomes of NSTEMI among patients with immune thrombocytopenia: a propensity matched national study.

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.

Apixaban vs Aspirin According to CHA2DS2-VASc Score in Subclinical Atrial Fibrillation: Insights From ARTESiA.

BACKGROUND: 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. OBJECTIVES: To help inform decision making, the authors evaluated the efficacy and safety of apixaban according to baseline CHA2DS2-VASc score. METHODS: We performed a subgroup analysis according to baseline CHA2DS2-VASc score and assessed both the relative and absolute differences in stroke/SE and major bleeding. RESULTS: Baseline CHA2DS2-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 CHA2DS2-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 CHA2DS2-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 CHA2DS2-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. CONCLUSIONS: One in 4 patients in ARTESiA with subclinical atrial fibrillation had a CHA2DS2-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 CHA2DS2-VASc score <4. A substantial intermediate group (CHA2DS2-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).

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.

Long-term outcomes of high bleeding risk patients undergoing percutaneous coronary intervention: a Korean nationwide registry.

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.

Temporal Changes in Long-Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant Era.

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<0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in Registry 2 than in Registry 1 (10.5% versus 9.5%, P=0.02), and the risk reduction of recurrent VTE in Registry 2 remained significant even after adjusting the confounders (hazard ratio [HR], 0.78 [95% CI, 0.65-0.93]; P=0.005). The cumulative 5-year incidence of major bleeding was not significantly different between the 2 registries (12.1% versus 13.7%, P=0.26), and the risk of major bleeding between the 2 registries was not significantly different even after adjusting the confounders (HR, 1.04 [95% CI, 0.89-1.21]; P=0.63). CONCLUSIONS: Along with the shift from warfarin to DOACs, there was a lower risk of recurrent VTE in the DOAC era than in the warfarin era, whereas there was no apparent change in the risk of major bleeding, which might still be an unmet need even in the DOAC era.

Clinical Implications of Polypharmacy for Patients with New-Onset Atrial Fibrillation Based on Real-World Data: Observations from the Korea National Health Insurance Service Data.

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.

Clinical and Economic Consequences of a First Major Bleeding Event in Patients Treated with Direct Factor Xa Inhibitors in Spain: A Long-Term Observational Study.

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.

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.

The impact of ticagrelor therapy on CABG-related bleeding in patients with STEMI managed with pPCI and following on-pump CABG.

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

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.

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.

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.

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.