Higher Risk Of Major Bleeding Research Articles

Platelet-fibrin clot strength and platelet reactivity predicting cardiovascular events after percutaneous coronary interventions.

Platelet-fibrin clot strength (PFCS) is linked to major adverse cardiovascular event (MACE) risk. However, the association between PFCS and platelet reactivity and their prognostic implication remains uncertain in patients undergoing percutaneous coronary intervention (PCI). In PCI-treated patients (n = 2512) from registry data from January 2010 to November 2018 in South Korea, PFCS using thromboelastography and platelet reactivity using VerifyNow were measured. High PFCS (PFCSHigh) was defined as thromboelastography maximal amplitude ≥ 68 mm, and high platelet reactivity (HPR) was defined as >208 P2Y12 reaction units. Patients were stratified into four groups according to maximal amplitude and P2Y12 reaction unit levels: (i) normal platelet reactivity (NPR)-PFCSNormal (31.8%), (ii) HPR-PFCSNormal (29.0%), (iii) NPR-PFCSHigh (18.1%), and (iv) HPR-PFCSHigh (21.1%). Major adverse cardiovascular event (all-cause death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years. High platelet reactivity and PFCSHigh showed an additive effect for clinical outcomes (log-rank test, P < .001). Individuals with NPR-PFCSNormal, NPR-PFCSHigh, HPR-PFCSNormal, and HPR-PFCSHigh demonstrated MACE incidences of 7.5%, 12.6%, 13.4%, and 19.3%, respectively. The HPR-PFCSHigh group showed significantly higher risks of MACE compared with the NPR-PFCSNormal group [adjusted hazard ratio (HRadj) 1.89; 95% confidence interval (CI) 1.23-2.91; P = .004] and the HPR-PFCSNormal group (HRadj 1.60; 95% CI 1.12-2.27; P = .009). Similar results were observed for all-cause death. Compared with HPR-PFCSNormal phenotype, NPR-PFCSNormal phenotype was associated with a higher risk of major bleeding (HRadj 3.12; 95% CI 1.30-7.69; P = .010). In PCI patients, PFCS and platelet reactivity demonstrated important relationships in predicting clinical prognosis. Their combined assessment may enhance post-PCI risk stratification for personalized antithrombotic therapy.

Clinical impact of renal function changes in patients with atrial fibrillation receiving anticoagulation with marginal renal function

Abstract Background Renal function changes were frequently observed in patients with marginal renal function. Renal function is one of crucial components to determine the doses and types of oral anticoagulants in atrial fibrillation (AF) patients and also closely associated with the risk of stroke and bleeding. However, the incidence of renal function changes and its impact on the clinical outcomes were not well-elucidated in anticoagulated AF patients. Purpose To evaluate renal function changes during follow-up in anticoagulated AF patients with marginal renal function defined as estimated glomerular filtration rate (eGFR) 45 to &amp;lt;60 ml/min/1.73m2. We also analysed the association between renal function changes and clinical outcomes. Methods Using a Korean nationwide claims database, we included anticoagulated AF patients who underwent a national health examination from January 2014 to December 2018 and also had follow-up examination within 2-year. Patients with eGFR 45 to &amp;lt;60 ml/min/1.73m2 at baseline examination were included. Based on the follow-up eGFR values, patients were categorised into three groups according to the change in renal function: maintained group (maintaining follow-up eGFR ranges from eGFR 45 to &amp;lt;60 ml/min/1.73m2), improved group (eGFR &amp;gt;60 ml/min/1.73m2), and aggravated group (eGFR &amp;lt;45 ml/min/1.73m2). After follow-up examination, ischemic stroke, major bleeding, end-stage renal disease (ESRD), all-cause death, and the composite of all clinical outcomes were evaluated. Results A total of 5126 patients were included: 42.3 % of patients (n=2170) maintained their renal function at follow-up examination, renal function of 44.4 % of patients (n=2276) were improved, whereas 13.3% of patients (n=680) were aggravated at follow-up examination. The mean eGFR values at baseline of maintained, improved, and aggravated groups were 54.2±4.1, 55.5±3.7, and 52.2±4.3 ml/min/1.73m2, respectively (p&amp;lt;0.001). The aggravated group was older, had higher CHA2DS2-VASc scores, and had more prevalent comorbidities, including hypertension, diabetes, prior myocardial infarction, and heart failure, than other groups. After multivariable adjustment, the aggravated group was associated with significantly higher risks of major bleeding, ESRD, all-cause death, and the composite outcome (HR [95% confidence interval], 1.46 [1.03-2.07], p=0.035; 1.49 [1.24-1.80], p&amp;lt;0.001; 9.29 [4.92-17.6], p&amp;lt;0.001; 1.57 [1.36-1.83], p&amp;lt;0.001, respectively). Conclusion In the anticoagulated AF patients with marginal renal function, a substantial proportion of patients (13%) experienced renal function decline below eGFR 45 ml/min/1.73m2 within 2-year. Renal function decline was associated with higher risks of major bleeding, ESRD, all-cause death and the composite outcome than those maintained their baseline renal function. Performing regular check-ups of renal function and protecting renal function should be emphasised in anticoagulated patients with AF and marginal renal function.

#430 Risk factors for major bleeding in patients with non-valvular atrial fibrillation and CKD G3-G5D on oral anticoagulants

Abstract Background and Aims We previously published a register-based cohort study comparing direct oral anticoagulants (DOAC) and warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) GFR category 3-5 (G3-G5) including patients on dialysis (G5D) (1). This study showed that DOAC was associated with lower risk of major bleeding but similar risk of ischemic stroke compared to warfarin. Bleedings were however more common than strokes, especially in advanced CKD (G5-G5D) where the risk of major bleeding was up to 10 times higher than the risk of stroke. Subsequently, the stroke- and bleeding risk in patients with AF and advanced CKD must be carefully evaluated when deciding on whether to prescribe oral anticoagulants (OAC) or not. Available stroke- and bleeding scoring systems do not perform well in CKD (2, 3). This study aims to present risk factors associated with major bleeding in a Swedish cohort of OAC-treated patients with CKD G3-G5D. Method Data was collected from high quality Swedish healthcare registers including Swedish Renal Registry and Auricula, a register for atrial fibrillation and oral anticoagulants and the National Patient Register. Patients with eGFR&amp;lt;60 ml/min/1.73m2 and non-valvular atrial fibrillation and either DOAC (apixaban, rivaroxaban, edoxaban and dabigatran) or warfarin treatment between 2009-2018 where included. DOAC treatment periods were collected from the Swedish Prescribed Drug Register (PDR), starting from dispense date covering assumed standard pill use and an additional 30 days grace period. Warfarin treatment periods were collected directly from Auricula. An undefined treatment was a period of no OAC or a period of warfarin from PDR not matching a treatment period in Auricula. All periods of OAC treatment with either DOAC or warfarin were evaluated in a multivariate Cox regression model regarding the risk of major bleeding requiring inpatient care. Time-dependent covariates adjusted for in the model were age, sex, years from study start, GFR category, congestive heart failure, diabetes mellitus, hypertension, excessive alcohol use, liver disease, vascular disease, previous gastrointestinal bleeding, intracranial bleeding, other bleeding, ischemic stroke/ transient ischemic attack (TIA), myocardial infarction, PCI and exposures (DOAC, warfarin and periods of undefined treatment). Results Of 2453 included patients, 59% had warfarin (time in therapeutic range, TTR, 67%) and 41% DOAC at inclusion, predominantly apixaban (81% of DOAC users). The mean age was 77 years, 28.3% had G3, 45.4% G4, 9.1% G5 and 17.3% G5D (Table 1). Mean follow up was 2.2 years. During follow up 424 major bleedings occurred yielding 8.9 (95% confidence interval 8.1-9.8) bleedings per 100 patient-years. Table 2 shows effect estimates of each covariate on the outcome major bleeding. Covariates, besides warfarin, associated with increased risk of major bleeding were GFR category, G5/5D versus G3, hazard ratio 1.92 (95% CI 1.43-2.56), previous GI bleeding, 1.77 (1.39-2.25) and previous other bleeding 1.33 (1.09-1.62). Other factors associated with major bleeding were congestive heart failure 1.36 (1.11-1.68), male sex 1.28 (1.03-1.60) and vascular disease, 1.35 (1.01-1.79). Conclusion Patients with non-valvular atrial fibrillation and CKD G3-G5D on OAC are at high risk of major bleeding. Previous major bleeding and kidney failure are strongly associated with major bleeding, this reiterates the results of many previous studies. The present study also shows an association between OAC-associated major bleeding in CKD and male sex, congestive heart failure and vascular disease. Similar associations have been showed in non-CKD cohorts previously but is inadequately studied in CKD. Knowledge about risk factors for major bleeding on OAC in advanced CKD is essential when deciding on when to anticoagulate or not.

Performance of risk scores in predicting major bleeding in left ventricular assist device recipients: a comparative external validation

BackgroundImplantation of a left ventricular assist device (LVAD) is a crucial therapeutic option for selected end-stage heart failure patients. However, major bleeding (MB) complications postimplantation are a significant concern. ObjectivesWe evaluated current risk scores’ predictive accuracy for MB in LVAD recipients. MethodsWe conducted an observational, single-center study of LVAD recipients (HeartWare or HeartMate-3, November 2010-December 2022) in the Netherlands. The primary outcome was the time to first post-LVAD MB (according to the International Society on Thrombosis and Haemostasis [ISTH] and Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS], and INTERMACS combined with intracranial bleeding [INTERMACS+] criteria). Mortality prior to MB was considered a competing event. Discrimination (C-statistic) and calibration were evaluated for HAS-BLED, HEMORR2HAGES, Anticoagulation and Risk Factors in Atrial Fibrillation, Outpatient Bleeding Risk Index, VTE-BLEED, AF-BLEED, and Utah Bleeding Risk Score (UBRS). ResultsOne hundred four patients were included (median age, 64 years; female, 20.2%; HeartWare, 90.4%; HeartMate-3, 9.6%). The cumulative MB incidence was 75.7% (95% CI 65.5%-85.9%) by ISTH and INTERMACS+ criteria and 67.0% (95% CI 56.0%-78.0%) per INTERMACS criteria over a median event-free follow-up time of 1916 days (range, 59-4521). All scores had poor discriminative ability on their intended prediction timeframe. Cumulative area under the receiving operator characteristic curve ranged from 0.49 (95% CI 0.35-0.63, VTE-BLEED) to 0.56 (95% CI 0.47-0.65, UBRS) according to ISTH and INTERMACS+ criteria and from 0.48 (95% CI 0.40-0.56, Anticoagulation and Risk Factors in Atrial Fibrillation) to 0.56 (95% CI 0.47-0.65, UBRS) per INTERMACS criteria. All models showed poor calibration, largely underestimating MB risk. ConclusionCurrent bleeding risk scores exhibit inadequate predictive accuracy for LVAD recipients. There is a need for an accurate risk score to identify LVAD patients at high risk of MB who may benefit from patient-tailored antithrombotic therapy.

Anticoagulation for Patients With Concomitant Atrial Fibrillation and End-Stage Renal Disease: A Systematic Review and Network Meta-Analysis.

Concomitant atrial fibrillation and end-stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well established to prevent thromboembolism, the applicability in patients under long-term dialysis remains debatable. The study aimed to determine the efficacy and safety of anticoagulation in the dialysis-dependent population. An updated network meta-analysis based on MEDLINE, EMBASE, and the Cochrane Library was performed. Studies published up to December 2022 were included. Direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, apixaban 2.5/5 mg twice daily), vitamin K antagonists (VKAs), and no anticoagulation were compared on safety and efficacy outcomes. The outcomes of interest were major bleeding, thromboembolism, and all-cause death. A total of 42 studies, including 3 randomized controlled trials, with 185 864 subjects were pooled. VKAs were associated with a significantly higher risk of major bleeding than either no anticoagulation (hazard ratio [HR], 1.47; 95% CI, 1.34-1.61) or DOACs (DOACs versus VKAs; HR, 0.74 [95% CI, 0.64-0.84]). For the prevention of thromboembolism, the efficacies of VKAs, DOACs, and no anticoagulation were equivalent. Nevertheless, dabigatran and rivaroxaban were associated with fewer embolic events. There were no differences in all-cause death with the administration of VKAs, DOACs, or no anticoagulation. For dialysis-dependent populations, dabigatran and rivaroxaban were associated with better efficacy, while dabigatran and apixaban demonstrated better safety. No anticoagulation was a noninferior alterative, and VKAs were associated with the worst outcomes.

Direct oral anticoagulant-associated bleeding complications in patients with gastrointestinal cancer and venous thromboembolism

BackgroundDirect oral anticoagulants (DOACs) have become widely used for cancer-associated venous thromboembolism (VTE). However, DOAC-associated bleeding complications remain challenging, especially in patients with gastrointestinal (GI) cancer. This study aimed to compare the bleeding outcomes between patients with upper or lower GI cancers and those without GI cancer. MethodsUsing the COMMAND VTE Registry-2 database, which is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020, we identified 1149 active cancer patients with DOACs (upper GI cancer: N=88; lower GI cancer: N=114; non-GI cancer: N=947). The primary outcome was major bleeding during anticoagulation therapy, which was evaluated in the competing risk regression model. ResultsThe upper GI cancer group had a lower mean body weight, and most often had anemia. The cumulative 5-year incidence of major bleeding was higher in the upper GI cancer group (upper GI cancer: 22.4%, lower GI cancer: 15.4%, and non-GI cancer: 11.6%, P=0.015). The most frequent major bleeding site in the upper GI cancer group was the upper GI (53%), followed by the lower GI (24%). After adjusting for the confounders, the excess risk in upper GI cancer relative to non-GI cancer remained significant for major bleeding (adjusted subhazard ratio, 2.25; 95%CI, 1.31-3.87, P=0.003), but that in lower GI cancer was insignificant. ConclusionsUpper GI cancer, but not lower GI cancer, as compared to non-GI cancer was associated with a higher risk for major bleeding during anticoagulation therapy with DOACs.Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htmUnique identifier: UMIN000044816.

Characteristics of traumatic major haemorrhage in a tertiary trauma center

BackgroundMajor traumatic haemorrhage is potentially preventable with rapid haemorrhage control and improved resuscitation techniques. Although advances in prehospital trauma management, haemorrhage is still associated with high mortality. The aim of this study was to use a recent pragmatic transfusion-based definition of major bleeding to characterize patients at risk of major bleeding and associated outcomes in this cohort after trauma.MethodsThis was a retrospective cohort study including all trauma patients (n = 7020) admitted to a tertiary trauma center from January 2015 to June 2020. The major bleeding cohort (n = 145) was defined as transfusion of 4 units of any blood components (red blood cells, plasma, or platelets) within 2 h of injury. Univariate and multivariable logistic regression analyses were performed to identify risk factors for 24-hour and 30-day mortality post trauma admission.ResultsIn the major bleeding cohort (n = 145; 145/7020, 2.1% of the trauma population), there were 77% men (n = 112) and 23% women (n = 33), median age 39 years [IQR 26–53] and median Injury Severity Score (ISS) was 22 [IQR 13–34]. Blunt trauma dominated over penetrating trauma (58% vs. 42%) where high-energy fall was the most common blunt mechanism and knife injury was the most common penetrating mechanism. The major bleeding cohort was younger (OR 0.99; 95% CI 0.98 to 0.998, P = 0.012), less female gender (OR 0.66; 95% CI 0.45 to 0.98, P = 0.04), and had more penetrating trauma (OR 4.54; 95% CI 3.24 to 6.36, P = 0.001) than the rest of the trauma cohort. A prehospital (OR 2.39; 95% CI 1.34 to 4.28; P = 0.003) and emergency department (ED) (OR 6.91; 95% CI 4.49 to 10.66, P = 0.001) systolic blood pressure < 90 mmHg was associated with the major bleeding cohort as well as ED blood gas base excess < -3 (OR 7.72; 95% CI 5.37 to 11.11; P < 0.001) and INR > 1.2 (OR 3.09; 95% CI 2.16 to 4.43; P = 0.001). Emergency damage control laparotomy was performed more frequently in the major bleeding cohort (21.4% [n = 31] vs. 1.5% [n = 106]; OR 3.90; 95% CI 2.50 to 6.08; P < 0.001). There was no difference in transportation time from alarm to hospital arrival between the major bleeding cohort and the rest of the trauma cohort (47 [IQR 38;59] vs. 49 [IQR 40;62] minutes; P = 0.17). However, the major bleeding cohort had a shorter time from ED to first emergency procedure (71.5 [IQR 10.0;129.0] vs. 109.00 [IQR 54.0; 259.0] minutes, P < 0.001). In the major bleeding cohort, patients with penetrating trauma, compared to blunt trauma, had a shorter alarm to hospital arrival time (44.0 [IQR 35.5;54.0] vs. 50.0 [IQR 41.5;61.0], P = 0.013). The 24-hour mortality in the major bleeding cohort was 6.9% (10/145). All fatalities were due to blunt trauma; 40% (4/10) high energy fall, 20% (2/10) motor vehicle accident, 10% (1/10) motorcycle accident, 10% (1/10) traffic pedestrian, 10% (1/10) traffic other, and 10% (1/10) struck/hit by blunt object. In the logistic regression model, prehospital cardiac arrest (OR 83.4; 95% CI 3.37 to 2063; P = 0.007) and transportation time (OR 0.95, 95% CI 0.91 to 0.99, P = 0.02) were associated with 24-hour mortality.ResultsEarly identification of patients at high risk of major bleeding is challenging but essential for rapid definitive haemorrhage control. The major bleeding trauma cohort is a small part of the entire trauma population, and is characterized of being younger, male gender, higher ISS, and exposed to more penetrating trauma. Early identification of patients at high risk of major bleeding is challenging but essential for rapid definitive haemorrhage control.

Effectiveness and Safety of Edoxaban Compared With Apixaban in Elderly Patients With Nonvalvular Atrial Fibrillation: A Real-World Population-Based Cohort Study.

The very elderly (≥80 years) are at high risk of nonvalvular atrial fibrillation and thromboembolism. Given its recent approval, the comparative effectiveness and safety of edoxaban in this population, relative to the commonly used apixaban, remain unknown. Using the United Kingdom Clinical Practice Research Datalink, we identified a cohort of patients aged ≥80 with incident nonvalvular atrial fibrillation and newly treated with edoxaban or apixaban between 2015 and 2021. Cohort entry was defined as the first prescription for one of the 2 drugs. We used propensity score fine stratification and weighting for confounding adjustment. A weighted Cox proportional hazards model was used to estimate the hazard ratios (HR) with 95% CI of ischemic stroke/transient ischemic attack/systemic embolism (primary effectiveness outcome) and of major bleeding (primary safety outcome) associated with edoxaban compared with apixaban. We also assessed the risk of all-cause mortality and a composite outcome of ischemic stroke/transient ischemic attack, systemic embolism, gastrointestinal bleeding, and intracranial hemorrhage as secondary outcomes. The cohort included 7251 new-users of edoxaban and 39 991 of apixaban. Edoxaban and apixaban had similar incidence rates of thromboembolism (adjusted rates, 20.38 versus 19.22 per 1000 person-years; adjusted HR, 1.06 [95% CI, 0.89-1.26]), although the rates of major bleeding were higher with edoxaban (adjusted rates, 45.57 versus 31.21 per 1000 person-years; adjusted HR, 1.42 [95% CI, 1.26-1.61]). The risk of the composite outcome was 21% higher with edoxaban (adjusted HR, 1.21 [95% CI, 1.07-1.38]). All-cause mortality was similar between edoxaban and apixaban (adjusted HR, 1.04 [95% CI, 0.96-1.12]). In very elderly patients with nonvalvular atrial fibrillation, edoxaban resulted in similar thromboembolism prevention as apixaban, although it was associated with a higher risk of major bleeding. These findings may improve the management of nonvalvular atrial fibrillation by informing physicians on the choice of anticoagulant for this vulnerable population.

The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis—a nationwide cohort study

BackgroundIn post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies.MethodsThis study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone.ResultsThe risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052–1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454—0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529—0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478—0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231—1.880), ICH (aHR 2.045, 95% CI 1.329—3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB.ConclusionsFor post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.

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

ObjectivesTo evaluate the safety of cangrelor administered concurrently with heparin or bivalirudin in patients on mechanical circulatory support. DesignA single-center, retrospective, cohort study of adult patient consecutively admitted between January 2016 and October 2020 SettingA tertiary medical center. ParticipantsAdult patients admitted to the cardiovascular intensive care unit initiated 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. InterventionsNone. Measurements and Main ResultsThe 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 receiving 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 our confidence interval was wide (adjusted hazard ratio [aHR] 1.93, 95% CI 0.61-6.11; p=0.262). ConclusionsPatients 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 on mechanical circulatory support.

Prognostic Significance of Heart Failure in Acute Pulmonary Embolism: A Comprehensive Assessment of 30-Day Outcomes.

Patients with heart failure (HF) are known to have an increased risk of pulmonary embolism (PE), but there is limited evidence regarding the prognostic implications of HF in patients with acute PE and the relationship between PE prognosis and left ventricular ejection fraction (LVEF). The primary objective of this study was the development of a composite outcome (mortality, major bleeding, and recurrence) within the first 30 days. The secondary objective was to identify the role of LVEF in predicting the development of early complications in patients with both HF and reduced LVEF. A prospective study was conducted at two tertiary hospitals between January 2012 and December 2022 to assess differences among patients diagnosed with acute PE based on the presence or absence of a history of HF. Cox regression models were employed to assess the impact of HF and reduced LVEF on the composite outcome at 30 days. Out of 1991 patients with acute symptomatic PE, 7.13% had a history of HF. Patients with HF were older and had more comorbidities. The HF group exhibited higher mortality (11.27% vs. 4.33%, p < 0.001) and a higher incidence of major bleeding (9.86% vs. 4.54%, p = 0.005). In the multivariate analysis, HF was an independent risk factor for the development of the composite outcome (HR 1.93; 95% CI 1.35-2.76). Reduced LVEF was independently associated with a higher risk of major bleeding (HR 3.44; 95% CI 1.34-8.81). In patients with acute pulmonary embolism, heart failure is independently associated with a higher risk of early complications. Additionally, heart failure with reduced LVEF is an independent risk factor for major bleeding.

Comparison of ticagrelor and clopidogrel in anemic patients with acute coronary syndrome: efficacy and safety outcomes over one year.

This retrospective study aimed to investigate the potential impact of ticagrelor and clopidogrel treatment on cardiovascular outcomes in patients with anemia and acute coronary syndrome (ACS) and to provide insights into the optimal therapeutic approach for this vulnerable patient population. A retrospective research design was employed, involving patients diagnosed with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) between 2014 and 2021. Inclusion criteria required a hemoglobin level below 12mg/dL and a minimum 12-month P2Y12 inhibitor treatment. Comprehensive clinical, biochemical, and echocardiographic data were collected from the hospital's electronic repository. The primary efficacy endpoint was major adverse cardiovascular events (MACE), encompassing total mortality, cardiovascular mortality, reinfarction, ischemic stroke, and hemorrhagic stroke. Major hemorrhage was the primary safety endpoint. Secondary outcomes included total mortality, cardiovascular mortality, reinfarction, ischemic stroke, and hemorrhagic stroke, individually. Patients treated with ticagrelor (n = 118) and clopidogrel (n = 538) were compared. No significant difference was observed in major adverse cardiovascular events (MACE) and major bleeding between ticagrelor and clopidogrel treatment groups (MACE: clopidogrel 10.0% vs. ticagrelor 11.0%, p = 0.75; major bleeding: clopidogrel 2.8%, ticagrelor 2.5%, p = 0.88). Patients with hemoglobin levels ≤ 8mg/dL demonstrated significantly higher MACE and major bleeding rates in the ticagrelor group (p = 0.008 and p = 0.002, respectively). Among patients aged ≥ 75 years, ticagrelor treatment was associated with a higher risk of major bleeding (p = 0.04). Ticagrelor and clopidogrel exhibited comparable efficacy and safety outcomes in anemic ACS patients over a one-year period. Although ticagrelor demonstrated superiority in reducing ischemic events, it is crucial to recognize the limitations of retrospective studies in informing clinical practice. This study offers valuable insights into tailoring antiplatelet therapy for anemic ACS patients and provides guidance for personalized treatment strategies, acknowledging the hypothesis-generating nature of retrospective analyses.

Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis.

Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations. Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI. Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83-1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09-3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83-1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments. According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Aspirin for the Primary Prevention of Cardiovascular Diseases in Patients with Chronic Kidney Disease: An Updated Meta-analysis.

Chronic kidney disease is associated with increased risk of cardiovascular diseases (CVD). This meta-analysis aims to evaluate the efficacy and safety of aspirin administered for primary prevention of CVD in patients with chronic kidney disease. PubMed, Scopus, Web of Science, CENTRAL and Clinicaltrials.gov were systematically searched from inception to 22 June 2023. Randomized controlled trials (RCTs) and cohort studies evaluating aspirin as primary prevention of CVD in chronic kidney disease were included. Meta-analysis was conducted using random-effects models. Overall, 11 studies (6 RCTs and 5 cohort studies) with 24,352 patients were included. The meta-analysis of RCTs indicated that aspirin was associated with lower risk of major adverse cardiovascular events [hazard ratio (HR): 0.79; 95% confidence intervals (CI): 0.64-0.97] and higher risk of major bleeding [risk ratio (RR): 1.35; 95% CI 1.15-1.58]. Incorporating observational evidence led to statistically non-significant findings in terms of risk of both cardiovascular events (pooled HR: 0.97; 95% CI 0.75-1.25; low certainty) and major bleeding (pooled RR: 1.21; 95% CI 0.99-1.48; moderate certainty). No statistically significant differences between aspirin and placebo were observed in the outcomes of mortality, coronary heart disease, stroke and renal events. RCT evidence points to a possible benefit in cardiovascular event reduction from aspirin administration, at the cost of increased major bleeding risk. This finding was not confirmed when the existing observational evidence was incorporated. Further research should determine the most appropriate subpopulation of chronic kidney disease patients that would benefit the most from prophylactic aspirin therapy. The study protocol has been prospectively registered and is publicly available from: https://doi.org/10.17504/protocols.io.261ged63jv47/v1 .

Dual Antiplatelet Therapy (DAPT) Versus Single Antiplatelet Therapy (SAPT) in Patients with Stroke Under 12 Hours: Meta-analysis and Systematic Review

Background: Patients with ischemic stroke under 12 hours are typically treated with antiplatelet therapy. Combining two antiplatelet medicines agents with differing actions and antithrombotic efficacy increases the risk of hemorrhage. Among 1000 patients with ischemic stroke, dual-antiplatelet therapy was associated with 1 to 7 more ICH events than clopidogrel monotherapy and seemed to provide no significant additional benefit in reducing ischemic stroke events. Method: Search in PubMed, EMBASE, and the Cochrane Central Register about dual antiplatelet therapy versus monotherapy. The research method used was PRISMA guidelines followed by literature exclusions. The inclusion criteria in this literature search were medicinal, literature from 2013-2023. Results: There is 5 literatures discussing the advantages of DAPT with the results obtained DAPT was not associated with a significant reduction in recurrent ischemic stroke [pooled RR 0.79 (95%CI 0.67-0.92)] but was associated with a higher risk of major bleeding [pooled RR 1.86 (95%IC 1.86-3.32)]. Conclusion: Immediate administration of DAPT &lt;12 hours after ischemic stroke can reduce recurrent stroke compared with antiplatelet monotherapy despite the increased risk of hemorrhage.

Dual-Frequency Ultrasound Assisted Thrombolysis in Interventional Therapy of Deep Vein Thrombosis.

Deep vein thrombosis (DVT) is one of the main causes of disability and death worldwide. Currently, the treatment of DVT still needs a long time and faces a high risk of major bleeding. It is necessary to find a rapid and safe method for the therapy of DVT. Here, a dual-frequency ultrasound assisted thrombolysis (DF-UAT) is reported for the interventional treatment of DVT. A series of piezoelectric elements are placed in an interventional catheter to emit ultrasound waves with two independent frequencies in turn. The low-frequency ultrasound drives the drug-loaded droplets into the thrombus, while the high-frequency ultrasound causes the cavitation of the droplets in the thrombus. With the joint effect of the enhanced drug diffusion and the cavitation under the dual-frequency ultrasound, the thrombolytic efficacy can be improved. In a proof-of-concept experiment performed with living sheep, the recanalization of the iliac vein is realized in 15min using the DF-UAT technology. Therefore, the DF-UAT can be one of the most promising methods in the interventional treatment of DVT.

Efficacy of Direct Oral Anticoagulants Vs Warfarin Vs Low Molecular Weight Heparin in the Treatment of Acute Splanchnic Vein Thrombosis in Patients with Underlying Myeloproliferative Disorder

Introduction: Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell disorders characterized by clonal proliferation of myeloid-lineage cells. Venous thrombosis poses a significant morbidity risk for MPN patients. The current recommended treatments for acute splanchnic vein thrombosis (SVT) are warfarin and low molecular weight heparin (LMWH). Direct oral anticoagulants (DOACs) are potential alternatives due to their predictable dose response and oral administration, but limited data exists for their use in acute SVTs. This retrospective study aims to assess the efficacy and outcomes of DOACs, LMWH, and warfarin in treating acute SVTs in patients with underlying MPN. Methods: We included patients of all ages with underlying myeloproliferative neoplasms and splanchnic vein thrombosis, with no underlying liver diseases, from Henry Ford Hospital Clinics in metropolitan Detroit, Michigan between 2013 and 2023. Patient data, which included age, gender, race, and BMI were recorded. The primary outcome was complete radiographic resolution (CRR) of the SVT, and secondary outcomes included recanalization, thrombosis progression, recurrent thrombosis, major bleeding, thrombocytopenia, and skin necrosis. The outcomes were compared between the three anticoagulant groups and patients using aspirin. Results: Among the 34 MPN patients with SVT, warfarin was prescribed most frequently (n=19), followed by enoxaparin (n=5) and DOACs (n=5). Although no significant differences were observed, warfarin showed the highest CRR rates (41.2%), while enoxaparin and DOACs had equal CRR rates (25%). DOACs showed recanalization rates similar to warfarin and higher than enoxaparin (44.4% and 47.1% vs. 20.0%, respectively). LMWH was associated with increased recurrent thrombosis rates (50.0%), while DOACs had a higher risk of major bleeding. All three anticoagulants had similar effects on thrombocytopenia and SVT progression. Aspirin use was linked to a higher risk of major bleeding (42.9%), but not using aspirin correlated with complete SVT resolution (30.8%), SVT progression (20.8%), recurrent thrombosis (29.2%), and thrombocytopenia (28.6%). Conclusions: Although limited by a small sample size, our study found no significant differences among the three anticoagulant groups. This contributes to establishing the role of DOACs in treating SVTs in patients with underlying MPN. Further studies with larger sample sizes are needed to explore the efficacy of DOACs compared to warfarin. Additionally, investigating the potential benefits of early thrombolysis in conjunction with anticoagulation for SVT patients with underlying MPN should be pursued, as the rates of complete resolution in these patients were low.

Safety and efficacy of direct oral anticoagulants in stroke prevention in patients with atrial fibrillation complicated with anemia and/or thrombocytopenia: a retrospective cohort study

BackgroundThere are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia.MethodsThis is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 109/L), Group 2 (hemoglobin male < 130 g/L; female < 120 g/L or platelet < 100 × 109/L), and Group 3 (hemoglobin male < 130 g/L; female < 120 g/L and platelet < 100 × 109/L). Patients in each category are further divided into two groups according to their stroke prevention strategies: rivaroxaban or dabigatran. Clinical results include major, minor, total bleeding, thrombosis, and the composite outcome of major bleeding and thrombosis.ResultsHigher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any event. Compared with Group 1, Group 2 had a higher risk of major bleeding (aOR 1.70, 95%CI 1.12–2.57, P = 0.012), and the composite endpoint of major bleeding and thrombosis (aOR 1.70, 95%CI 1.19–2.44, P = 0.004). Compared with Group 1, Group 3 had a higher total bleeding risk (aOR 2.15, 95%CI 1.14–4.05, P = 0.018). Compared with dabigatran, rivaroxaban was associated with higher composite risk in Group 1 (aOR 2.91, 95% CI 1.66–5.16, P < 0.001) and Group 2 (aOR 3.05, 95%CI 1.46–6.39, P = 0.003), but there was no significant difference in Group 3 (aOR 1.78, 95%CI 0.23—13.54, P = 0.577).ConclusionsHigher hemoglobin levels are associated with a reduced risk of total bleeding and major bleeding in patients with AF. Dabigatran was associated with better clinical outcomes than rivaroxaban in patients with anemia or thrombocytopenia but not in those with anemia and thrombocytopenia.

Clinical Outcomes in Patients With Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants Across Varying Body Mass Index.

Background There are conflicting data on outcomes in patients with atrial fibrillation treated with non-vitamin K oral anticoagulants across varying body mass index (BMI). We investigated cardiovascular and bleeding risk in patients with atrial fibrillation with varying BMI. Methods and Results Observational cohort study from the Swedish oral anticoagulation registry between August 2, 2011, and December 31, 2018. Primary outcomes were mortality, ischemic stroke/systemic embolism, and major bleeding. Baseline BMI (kg/m2) was analyzed continuously and categorized: underweight (<18.5 kg/m2), normal weight (18.5 to <25 kg/m2), preobesity (25 to <30 kg/m2), and obesity class I to III (30 to <35, 35 to <40, and ≥40 kg/m2). Adjusted Cox models and nonlinear relationships of BMI were modeled using restricted cubic splines. Non-vitamin K oral anticoagulant-treated patients with atrial fibrillation were included (n=26 047). At baseline, 602 (2.3%) were underweight, 9101 (34.9%) were normal weight, 9970 (38.3%) were preobese, 4280 (16.4%) were obese class I, 1486 (5.7%) were obese class II, and 608 (2.3%) were obese class III. Underweight and obesity class III were in adjusted continuous analysis associated with increased mortality and major bleeding, with lowest risk observed among preobese patients with BMI 28.2 and 26.2 kg/m2, respectively. In adjusted categorical analysis, underweight was associated with increased mortality (hazard ratio [HR], 1.77 [95% CI, 1.57-1.99]) and nonsignificant higher risk of major bleeding (HR, 1.23 [95% CI, 0.95-1.58]). Similarly, obesity class III was associated with increased mortality (HR, 1.67 [95% CI, 1.40-1.99]) and major bleeding (HR, 1.68 [95% CI, 1.29-2.17]). No significant association was observed between higher BMI and ischemic stroke/systemic embolism. Conclusions In non-vitamin K oral anticoagulant-treated patients with atrial fibrillation, there appears to be a U-shaped relationship between BMI and mortality and major bleeding.

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

Abstract Background Patients on double antiplatelet treatment who need early in-hospital coronary artery bypass grafting (CABG) are at high risk of major bleeding. However, recent studies have demonstrated that early CABG surgery within 7 days of discontinuation of p2Y12 inhibitors are safe with respect to bleeding events in patients with acute coronary syndrome. Purpose 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). Methods Patients with the diagnosis of STEMI who were managed with pPCI and underwent subsequent early (4-7 days following pPCI) or delayed (&amp;gt; 7 days following pPCI) 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. Results The study cohort included 98 patients. Fifty-four (54%) patients underwent early and 44(45%) patients underwent delayed CABG surgery. Left main coronary artery involvement and presence of chronic total occlusion in the non-infarct related artery were 26.5% and 25.5%. 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 was an independent predictor of CABG-related bleeding (OR:0.720, p: 0.034).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. Conclusion 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.