Bleeding Rates Research Articles

Distal versus conventional transradial access for coronary angiography: a pooled analysis from the randomized RAPID trial

Abstract Background Transradial access (TRA) is the recommended approach for coronary procedures considering safety benefits over femoral access with radial artery occlusion (RAO) being the most frequent complication. Although usually not clinically significant, the presence of RAO affects potential future procedures and medical treatments. Distal TRA (dTRA) has been suggested to reduce the risk of postprocedural RAO compared to conventional TRA (cTRA) with, however, inconsistent results in clinical trials. Purpose This study aimed to compare the efficacy and safety of dTRA versus cTRA in patients undergoing diagnostic coronary angiography. Methods The RAPID trial is a single-center, open-label, 2x2 factorial, randomized study of patients undergoing coronary angiography through a 6-F radial access. The trial was stopped early by the data and safety monitoring board after the second pre-planned interim analysis and inclusion of 600 participants. Patients were randomized to dTRA or cTRA with further stratification according to periprocedural heparin use and preexisting oral anticoagulation. The primary endpoints were the incidence of RAO assessed by vascular ultrasound and puncture-site related bleedings. Results The final study population consisted of 298 patients randomized to dTRA and 302 patients to cTRA. Periprocedural heparin was administered in 382 patients (63.7%) and percutaneous coronary intervention was performed in 161 cases (26.8%) without differences between the study groups (p=0.700 and p=0.465; respectively). Distal TRA was associated with a significantly increased number of puncture attempts (2.4 ± 2.0 versus 1.5 ± 1.2; p<0.001) and failed punctures leading to access site crossover (11.7% versus 5.0%; p=0.003). Consequently, the total procedure time was longer in the dTRA group (30 min versus 25 min; p=0.004) without increasing fluoroscopy time (p=0.320), dose area product (p=0.245), or contrast volume (p=0.884). Patent hemostasis was achieved in 91.7% of patients with cTRA. The rates of RAO (16.1% versus 15.6%, p=0.855) and puncture-site related bleedings (6.7% versus 8.3%; p=0.466) were similar in both groups. Conclusions According to this study, dTRA does not reduce the risk of RAO or bleeding events compared to cTRA.

Prognostic implications of p2y12 inhibitor pre-treatment in non-st segment elevation acute coronary syndromes undergoing late invasive strategy - a national registry analysis

Abstract Background Current guidelines recommend considering P2Y12 pre-treatment (PreT) in patients (pts) with non-ST segment elevation acute coronary syndrome (NSTE-ACS) expected to undergo a late invasive strategy, based on individual bleeding risk. Purpose Investigate in-hospital morbidity and mortality in NSTE-ACS pts undergoing a late invasive strategy (coronary angiography (CAG) performed >24h post-admission) comparing those receiving P2Y12 inhibitors (P2Y12i) PreT with those who did not. Methods Retrospective multicenter analysis of NSTE-ACS pts from the Portuguese Registry on Acute Coronary Syndromes (ProACS) undergoing a late invasive strategy from October 2010 to October 2023. Exclusion criteria: previous treatment with P2Y12i or anticoagulants; atrial fibrillation. Two cohorts were defined: pts receiving PreT with P2Y12i before undergoing CAG (group 1) and pts without PreT (group 2). Comparative analyses included baseline characteristics, clinical findings, CAG findings and treatment. Primary outcome was in-hospital major adverse cardiovascular events (MACE), a composite of all-cause mortality, re-infarction, stroke and congestive heart failure. The secondary outcome included individual events and major bleeding. Results 3776 pts were included (mean age:66±12 yrs,29% female), 1530 in group 1 and 2246 in group 2. Group 1 had lower prevalence of dyslipidemia (60 vs 66%, p<0.001), prior stroke (7 vs 5%, p=0.003), myocardial infarction (16 vs 21%) and percutaneous coronary intervention (12 vs 15%) (both p=0.001). On admission, there were no differences regarding Killip-Kimball class (class I - 90 vs 90%,p=0.501) and pts in group 1 less frequently had left ventricular disfunction (left ventricular ejection fraction <50% - 20 vs 24%,p=0.032). Group 1 had higher incidence of obstructive CAD (84 vs 77%,p<0.001), more frequently required more than 1 CAG during admission (8 vs 4%,p<0.001), but multivessel disease did not significantly differ (52 vs 52%,p=0.667). Coronary angioplasty was more frequent in group 1 (63 vs 60%,p=0.019) as was coronary artery bypass graft (13 vs 10%,p=0.002). Regarding anti-thrombotics, group 1 had higher prescription rates of clopidogrel (68 vs 56%), aspirin (99 vs 81%), unfractionated heparin (21 vs 8%), enoxaparin (80 vs 56%), but lower of fondaparinux (12 vs 41%) (all p<0.001). There were no differences in the primary outcome (9 vs 9%,p=0.906) and secondary outcomes: in-hospital mortality (1 vs 1%), re-infarction (1 vs 1%), ischemic stroke (1% vs 0,4%) and congestive heart failure (7% vs 8%) (all p>0.05). Group 1 had higher rates of major bleeding (0.8 vs 0.2%, OR 3.48, CI 95% 1.22-9.89, p=0.013). Conclusions In patients with NSTE-ACS undergoing a late invasive strategy, PreT with P2Y12i showed no statistically significant differences in MACE, despite association with higher rates of major bleeding.Baseline characteristicsPrimary and secondary outcomes

Real-world implementation of a genotype-guided p2y12-inhibitor de-escalation strategy in acute coronary syndrome patients

Abstract Background CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel, may optimize the balance between ischemic and bleeding risk in ACS patients. Purpose Compare bleeding and ischemic event rates in genotyped patients versus standard care. Methods Since 2015, ACS patients in the FORCE-ACS registry received standard dual antiplatelet therapy (DAPT). Since 2021, immediate genotype-guided P2Y12-inhibitor de-escalation was applied, switching non-carriers of the loss-of-function allele CYP2C19*3 or CYP2C19*2 from ticagrelor or prasugrel to clopidogrel, while loss-of-function carriers, carrying at least one loss-of-function allele, remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction (MI) or stroke and the primary bleeding endpoint, BARC 2, 3, or 5 bleeding, were compared between genotyped those on standard DAPT after one year. Results Among 5,321 enrolled ACS patients, 406 underwent genotyping, compared with 4,915 non-genotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n=265) were non-carriers, whereas 34.7% (n=141) were loss-of-function carriers. The primary ischemic endpoint occurred in 5.2% of patients in the genotyped cohort compared to 6.9% in the standard care cohort (adjHR 0.88, 95% CI 0.56–1.38). The rate of the primary bleeding endpoint was lower in the genotyped cohort compared to the standard care cohort (4.7% vs. 9.8%; adjHR 0.50, 95% CI 0.31-0.78). Conclusion These results demonstrate the feasibility of a CYP2C19 genotype-guided P2Y12-inhibitor de-escalation strategy in a real-world ACS population. This strategy reduced bleeding events, while ischemic events were not increased as compared to a standard DAPT regime.Primary ischemic endpointBARC 2, 3 or 5 bleeding

Analysis of safety and outcome of use of NOAC in intracardiac thrombi over warfarin

Abstract Introduction Intracardiac clots occur in 15- 25% of patients post myocardial infarction and in patient with atrial fibrillation. It holds poor outcome if not treated with anticoagulation. Warfarin remains the drug of choice in such patients, however recently according to the newly published data, the European Society of Cardiology (ESC) has recommended non-vitamin K antagonist anticoagulant (NOAC) for intracardiac clots as a class 2A recommendation. There is no documented data in the region of the gulf regarding the use of NOAC in intracardiac clots. Aim We aim in this study to evaluate the use of NOAC in the treatment of intracardiac clots over warfarin, by studying the effectiveness, safety and associated complications. Methodology A retrospective cohort study from April 2017 to December 2023 was conducted of patient’s above 18 years old who have a documented intracardiac clot on echocardiography. The patient were grouped into patients discharged on NOAC and those discharged on warfarin. The participants were studied for resolution of clot and development of complication; death, bleeding and thrombosis. Results A total of 253 patients fulfilled the inclusion criteria. Out of which 45 ( 18%) patients were discharged on NOAC and 208 (82%) on warfarin. The two groups had similar demographics with equally mean age of 71 years old , 89% being males, 38% hypertensive and most common clot in the left ventricle in both groups. From those patients with documented follow up ( NOAC 45% average of 8 months, Warfarin 62% average of 7 months); 48% in the NOAC group had a documented resolution of the clot while 44% in the warfarin group had a documented resolution of the intracardiac clot.(p value of 0.7) The median resolution time in the NOAC group was 4 months while in the warfarin group 3.5 months. Bleeding occurred in 19% and mortality rate was 5% in NOAC group, while in the warfarin group 10% developed bleeding and mortality rate was 6%. Conclusion Our data pointed out the safety of NOAC as a reasonable alternative to warfarin inpatient with intracardiac clots emphasizing the ESC recommendation in this regards. We recommend a randomized studies to prove the superiority of NOAC as anticoagulation of choice in intracardiac thrombi.

A cohort study examining predictors of stroke and bleeding among people with congenital heart disease and atrial fibrillation

Abstract Background Congenital Heart Disease (CHD) is associated with development of atrial fibrillation (AF) at an early age. With increased survival of this cohort into adulthood, the prevalence of concurrent CHD and AF is expected to increase over the next several decades. Little is known about the utility of clinical risk factors or prediction models in determining bleeding or stroke rates in adults with CHD and AF. Purpose This study aims to measure the performance of the CHADSVASC and HASBLED scores in a cohort of people with CHD. The association between traditional stroke and bleeding risk factors, as well as CHD-specific factors, will be quantified. Methods Patients age 18 or older attending one of three centers in the USA were included in this study if they had a history of AF on ECG, holter monitor or device interrogation, in addition to a diagnosis of Tetralogy of Fallot (TOF), Double Outlet Right Ventricle (DORV), or Pulmonary Atresia with Intact Ventricular Septum (PA-IVS). Outcomes were major bleeding event, and stroke rate. Analysis was conducted using cox univariable regression controlling for current age. Receiver operator curve and c-statistics were produced for the CHADSVASC and HASBLED scores respectively. Results 326 people were included in this study, of whom 161 (49.5%) had TOF secondary to Pulmonic Stenosis, 126 (38.8%) had TOF secondary to Pulmonary Atresia, 25 (7.7%) had DORV, and 155 (47.7%) had PA-IVS. 227 people used warfarin (79.4%), 28 (9.8%) used apixaban, 9 (3.1%) used Rivaroxaban, 3 (1%) used Edoxaban, and 5 (1.7%) used Enoxaparin for a period of at least 30 days during the study. 13 (4.5%) people didn’t receive anticoagulation during the study. 26 people had a stroke (8.8%) while 85 people (28.6%) had a major bleeding event. Only the CHADSVASC score was significantly associated with stroke rates (HR 2.103, 95% CI 1.555 to 2.844, p<0.001). Clinical variables, such as subtype of CHD, prior conduit placement or unifocalization were not associated with stroke or major bleeding events. C-statistic for the CHADSVASC score in predicting stroke events was 0.755 (Figure 1). C-statistic for the HASBLED score in predicting major bleeding was 0.442 (Figure 2). Conclusions Among people with CHD and AF, the CHADSVASC score can robustly predict stroke events. Other clinical variables are less valuable in predicting either bleeding or strokes. The HASBLED score likely doesn’t have a role in predicting major bleeding episodes in this cohort.

Low rates of haemorrhagic stroke, not increased by age, renal/hepatic impairment, concomitant anti-platelet use and high CHA2DS2-VASc scores, in the 4-year follow-up of ETNA-AF-Europe

Abstract Background Balancing the risks of stroke and bleeding is necessary to optimise oral anticoagulation use in clinical practice. Concerns remain over the increased bleeding risk in patients receiving NOACs, and long-term safety data in this population are limited. Purpose To report annualised rates of haemorrhagic stroke in various sub-populations of patients with atrial fibrillation (AF) treated with edoxaban during the 4-year follow-up of ETNA-AF-Europe. Methods ETNA-AF-Europe, a post-authorisation, observational study conducted across 776 sites from 10 European countries, assessed the risks and benefits of edoxaban use in patients with AF. Here, we present the annualised event rates of haemorrhagic stroke during the 4-year follow-up, that occurred overall (on-/off-edoxaban) and on-edoxaban, including sub-populations stratified by age, renal impairment, hepatic impairment, chronic concomitant antiplatelet use and CHA2DS2-VASc score. Patient characteristics were collected at baseline and annualised event rates were reported for outcomes. Results A total of 13,164 patients were included in the full analysis set. Baseline characteristics are reported in Table 1. The overall and on-edoxaban annualised haemorrhagic stroke rates were low (number of events, % [95% confidence interval]: 36, 0.1 [0.05;0.11] and 31, 0.1 [0.05;0.10] respectively). The overall haemorrhagic stroke rates remained low in subgroups stratified by age (<65 years: 4, 0.1 [0.00;0.11]; ≥65–75 years: 13, 0.1 [0.04;0.13]; ≥75 years: 19, 0.1 [0.05;0.12]), renal impairment (yes: 23, 0.1 [0.05;0.13]; no: 12, 0.1 [0.03;0.11]), hepatic impairment (yes: 0, 0.0 [0.00;0.00]; no: 35, 0.1 [0.06;0.11]), concomitant antiplatelet use (yes: 2, 0.1 [0.00;0.16]; no: 34, 0.1 [0.05;0.11]) and CHA2DS2-VASc score (low [0–1]: 0, 0.0 [0.00;0.00]; moderate [2–4]: 28, 0.1 [0.06;0.12]; high [>4]: 7, 0.1 [0.03;0.18]) (Figure). Likewise, on-edoxaban haemorrhagic stroke rates were low irrespective of age (<65 years: 3, <0.1 [0.00;0.010; ≥65–75 years: 12, 0.1 [0.04;0.13]; ≥75 years: 16, 0.1 [0.04;0.12]); renal impairment (yes: 20, 0.1 [0.05;0.12]; no: 10, 0.1 [0.02;0.10]); hepatic impairment (yes: 0, 0.0 [0.00;0.00]; no: 30, 0.1 [0.05;0.11]); chronic concomitant antiplatelet use (yes: 2, 0.1 [0.00;0.18; no: 29, 0.1[0.05;0.10]) or CHA2DS2-VASc score (low [0–1]: 0, 0.0 [0.00;0.00]; moderate [2–4]: 25, 0.1 [0.05;0.12]; High [>4]: 6, 0.1 [0.02;0.17]) (Figure). Conclusions The overall and on-edoxaban annualised rates of haemorrhagic stroke were low and were not increased by non-modifiable risk factors such as age, renal/hepatic impairment, concomitant antiplatelet use and high CHA2DS2-VASc scores during the 4-year follow-up. The overall annualised rates on-edoxaban in ETNA-AF-Europe registry are quite comparable with incidence rates reported in the literature in age-stratified populations (incidence/100 person-years: 55-64 years: 0.06 [0.04-0.07]; 65-74 years: 0.1 [0.09-0.1]; 75-84 years 0.2 [0.1-0.2]).Baseline Characteristics

The efficacy and safety of NOAC in very elderly atrial fibrillation patients; data from the Korean national health insurance cohort registry

Abstract Background Data regarding efficacy and safety on anticoagulation in very elderly atrial fibrillation patients are relatively sparse. Purpose We investigated the clinical benefit of anticoagulation with NOAC in very elderly AF patients through national healthcare insurance registry. Methods Clinical data of 862,935 patients who were diagnosed with AF from 2015 to 2020 were collected for analysis. Patients under the age of 85, prior history of ICH, GI bleeding and prior prescription days of aspirin, warfarin and NOAC exceeding 90 along with follow up period less than 90 days were excluded. Results A total of 10,625 patients were eligible for analysis. Patients with OAC (HR: 0.60, 95% CI 0.53-0.69), p<0.001) showed higher efficacy regarding systemic embolism compared to aspirin (HR: 0.84, 95% CI 0.74-0.95, p=0.008) and no treatment group. Individual comparison of NOAC and aspirin via propensity score matching showed that patients with NOAC (HR: 0.71, 95% CI 0.61-0.85), p<0.001) showed higher event free survival regarding systemic embolism compared to aspirin. Bleeding risk was also higher for NOAC (HR: 1.28, 95% CI 1.07-1.56, p=0.006) group but did not result in commensurate increase in mortality (HR:0.60, 95% CI 0.45-0.81, p<0.001). Conclusions Anticoagulation with NOAC in very elderly patient showed higher event free survival regarding systemic embolism. Despite having higher event rate of bleeding, eventual death did not show any association with NOAC.

Evaluation of bleeding events in a cohort of patients with transthyretin cardiac amyloidosis

Abstract Introduction and purpose transthyretin amyloidosis is an infiltrative disease with several comorbidities, including bleeding. The aim of this study was to evaluate the incidence of bleeding in patients with transthyretin amyloidosis and the underlying risk factors that promote bleeding. Methods a retrospective observational study was conducted on a cohort of patients with transthyretin amyloidosis diagnosed between 2016 and 2023 according to the diagnostic criteria of the Working Group on Myocardial and Pericardial Diseases of the European Society of Cardiology. Bleeding risk was calculated according to HAS-BLED score and bleeding events at follow-up were analysed. Results 184 patients were diagnosed with a median age of 84 years [IQR 79-8], 154 (8%) males. 123 patients (67%) were on anticoagulant therapy. 91 patients (50%) had a bleeding event, with a total of 189 events recorded and a median time from transthyretin amyloidosis diagnosis to bleeding of 10 months [IQR 6-14]. The most frequent bleeding sites were gastrointestinal (32%) and cutaneous (22%). 35 patients (39%) had a haemorrhage which fulfilled severe bleeding criteria and 4 patients died of haemorrhagic causes. As a consequence of bleeding, 6 atrial appendage closure were indicated and anticoagulation therapy was modified in 15 individuals. The incidence rate of haemorrhage was 50 bleeds per 100 patient-years and 58 per 100 patient-years in patients on anticoagulant treatment. Anticoagulant therapy resulted in a 3,5-fold raise in bleeding (95% CI 2-7) and a punctuation ≥2 in HAS-BLED score increased haemorrhages 4,6 times (95% CI 2-9), with higher rates of bleeding the higher the score on the scale. Conclusions bleeding is a frequent complication in transthyretin amyloidosis, with a higher risk in those individuals with anticoagulant therapy or with a HAS-BLED score ≥2. Subsequently, it should be considered in the follow-up both haemorrhagic risk and anticoagulant treatment, with the aim of implementing strategies to reduce the bleeding risk.

Effect of tranexamic acid in vascular surgery- a sub-study of the POISE-3 randomized clinical trial

Abstract Background/Introduction In the POISE-3 trial involving patients undergoing noncardiac surgery, tranexamic acid (TXA) reduced the incidence of the composite outcome of life-threatening bleeding, major bleeding, or bleeding into a critical organ at 30 days. Bleeding is a major issue in vascular surgery. However, TXA use may be limited due to concerns about its safety in this high-risk population. With 1,399 participants in POISE-3 undergoing vascular surgery, this is the largest trial assessing TXA's efficacy in this population. Purpose In this post hoc subgroup analysis, we aimed to investigate the interaction between surgery type (vascular/non-vascular) and the effects of TXA vs placebo on bleeding and cardiovascular (CV) safety outcomes in the POISE-3 population. Methods: Eligible patients were ≥45 years, undergoing inpatient noncardiac surgery, and at risk for bleeding and CV complications. Patients were randomised (1:1) to TXA 1 gm IV bolus at start and end of surgery (total 2 gm) or placebo. We used Cox proportional hazards models incorporating tests for interaction to analyse time to the first occurrence of the composite bleeding outcome, and the CV safety outcome (composite of myocardial injury after noncardiac surgery, non-hemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism) at 30 days. Estimates of hazard ratios (HR) with 95% confidence intervals (CI) were calculated for each subgroup with the interaction P value. Results 9,468 of 9535 (99.3%) POISE-3 patients are included in this analysis; 1399 of whom underwent vascular surgery (699 TXA, 700 placebo). Majority (89.8%) of the vascular surgeries were aorto-iliac, peripheral vascular and extracranial surgeries. In the vascular surgery group, 12.6% of patients receiving TXA experienced the composite bleeding outcome versus 14.7% with placebo (HR 0.85, 95% CI 0.64-1.13). For non-vascular surgery patients, these rates were 8.6% with TXA and 11.3% with placebo (HR 0.74, 95% CI 0.65-0.86), with an interaction P value of 0.42. In vascular surgery patients, the CV safety outcome occurred in 20.2% with TXA versus 18.1% with placebo (HR 1.12, 95% CI 0.88-1.42). In the non-vascular surgery group, both TXA and placebo arms showed a 13.1% incidence rate (HR 1.00, 95% CI 0.89-1.13), with an interaction P value of 0.43. Conclusion In vascular surgery patients, there were higher rates of bleeding and cardiovascular events compared to those undergoing non-vascular surgeries; however, there was no significant interaction between the effects of TXA and the type of surgery. The overall POISE-3 trial provides the best estimate of effect with TXA for all patients including those undergoing vascular surgery. The main limitation is that this subgroup analysis was not pre-specified.

Comparing the real-world and clinical trial bleeding rates associated with oral anticoagulation treatment for atrial fibrillation

Abstract Background The prevention of stroke in patients with atrial fibrillation (AF) involves the use of oral anticoagulation, commonly in the form of direct oral anticoagulants (DOAC). However, it comes with an increased risk of bleeding and therefore, counselling patients on their individual risk is important. Although majority of patients initiated on DOAC have been represented within the clinical trials, there are some cohorts which are under-represented in whom clinicians are unable to practice evidence-based medicine. Methods Utilising the pooled clinical trial (CT) data sourced from Medidata Enterprise Data Store, 5 recent open-label industry sponsored AF trials were compared with Real-World data (RWD) was sourced from the HealthVerity Marketplace with the occurrence of bleeding events as the primary outcome of interest. Results A total of 64,421 patients were included in the analysis, with 3207 patients from the clinical DOAC trials and 61,214 patients from the RWD cohort. Overall, the patients from RWD cohort had more co-morbidities, were older (72.2 ± 11.9 vs 65.3 ±10.7 years old, p<0.001), had higher mean CHA2DS2VASc (3.98 ± 1.9 vs 2.87 ± 1.73, p<0.001) and HAD-BLED scores (2.13 ± 1.02 vs 1/04 ± 0.93, p<0.001) when compared to the trial data. When comparing the incidence of first major bleed at 12 months post treatment initiation, rates in the RWD cohort was significantly higher (10.69 vs 18.97 per 100 person-years). The impact of comorbidities such as age, CHA2DS2VASc and HAD-BLED scores were similar in both cohorts, however, there was an under-representation of older, females and more co-morbid patients within the clinical trial cohort. Conclusion DOAC treated patients have higher bleeding incidence rate in the RWD cohort as compared to clinical trials. This can be explained by the older patient age group with more complex medical histories and higher HAS-BLED scores. The under-representation of higher risk patients and lower proportion of females within clinical trials should be addressed to better translate clinical trial data into real world clinical practice.

Oral anticoagulants or antiplatelets for cryptogenic stroke: a systematic review and meta-analysis

Abstract Background Cryptogenic strokes comprise 20 to 30% of ischemic strokes and include a substantial proportion classified as embolic stroke of undetermined source (ESUS). However, the optimal antithrombotic strategy for cryptogenic stroke remains contentious. Purpose We conducted a systematic review and meta-analysis to compare the efficacy and safety of oral anticoagulants (OAC) versus antiplatelets in patients with cryptogenic stroke. Methods Six electronic databases of PubMed, Embase, Web of Science, the Cochrane Library, Google Scholar and ClinicalTrials.gov were searched from inception to Feb 15, 2024 to identify relevant randomized controlled trials (RCTs) comparing stroke recurrence and major bleeding rates between OAC and antiplatelets in cryptogenic stroke patients. We included trials adhering to a stringent diagnostic work-up for cryptogenic stroke, defined as cerebral infarction not attributed to definite sources of cardioembolism, large artery atherosclerosis, or small artery disease despite undergoing comprehensive investigations. The primary outcome was recurrent ischemic stroke, and the secondary outcome was major bleeding based on International Society of Thrombosis and Hemostasis criteria. Subgroup analysis was conducted for ESUS patients with an increased risk of cardiac emboli, such as patent foramen ovale (PFO) and atrial cardiopathy, defined as lead V1 terminal P-wave > 5000 μV × ms in electrocardiogram, serum N-terminal pro-B-type natriuretic peptide level > 250 pg/mL, and left atrial diameter (LAE) > 4 cm, or LAE index ≥ 3 cm/m2 on echocardiogram. Hazard ratio (HR) with 95% confidence (CI) was used as a measure of the effect estimates for aforementioned outcomes. Random-effects meta-analysis was performed using a restricted maximum likelihood model given between-study variance is inevitable. Results Our meta-analysis included 9 RCTs with a total of 15,139 patients (OAC = 7,343; antiplatelets = 7,796). ARCADIA, RE-SPECT ESUS, and NAVIGATE ESUS Trial investigated apixaban, dabigatran, and rivaroxaban, respectively, while warfarin was primarily used as OAC in the remaining six trials. Aspirin was predominantly utilized for antiplatelet therapy. There was no significant difference in recurrent ischemic stroke between OAC and antiplatelets (HR, 0.90; 95% CI, 0.78 to 1.04; I2 = 0%). However, OAC use was associated with a significantly higher risk of major bleeding (HR, 1.66; 95% CI, 1.07 to 2.56; I2 = 36%). Subgroup analysis in ESUS patients revealed comparable rates of recurrent ischemic stroke in those with atrial cardiopathy (HR, 0.91; 95% CI, 0.65 to 1.29; I2 = 0%) and PFO (HR, 0.72; 95% CI, 0.49 to 1.07; I2 = 0%). Conclusions Our meta-analysis suggests that OAC use does not decrease the risk of recurrent ischemic stroke compared with antiplatelet use but is associated with a significantly higher risk of major bleeding in patients with cryptogenic stroke.Primary (A) and secondary (B) outcomesSubgroup analysis for recurrent stroke

Ischemic and bleeding risk after ST-segment elevated myocardial infarction in patients with active cancer

Abstract Background Treatment of patients with cancer presenting with ST-elevation myocardial infarction (STEMI) is complex given the increased risk of both thrombotic and major bleeding complications. We evaluated the risk of major bleeding and re-infarction in patients with or without cancer following admission with STEMI Methods A nationally-linked cohort of STEMI patients between January 2005 and March 2019 were obtained from the UK Myocardial Infarction National Audit Project (MINAP) registry and the UK national Hospital Episode Statistics Admitted Patient Care (HES APC) registry. Cox proportional hazard models were used, and Kaplan-Meier survival and cumulative survival curves were constructed. Results A total of 322,776 STEMI indexed admissions were identified between Jan 2005 and March 2019. Of those, 7050 (2.2%) patients were diagnosed with active cancer. Cancer patients were older with more cardiovascular comorbidities. Cancer patients received invasive coronary angiography (62.2% vs 72.7%, p<0.001) and PCI (58.4% vs 69.5%) less often compared to patients without cancer and were less likely to be prescribed DAPT (85% vs 95.4%). Major bleeding rate at one year was higher in cancer patients (6.5% vs 3.5%) while re-infarction rates were similar (cancer 5.7%, no cancer 5.1%). Adjustment for differences in baseline covariates, a similar risk of re-infarction (SHR 1.10, 95% CI 0.94-1.27) and a 50% increased risk of major bleeding (SHR 1.49, 95% CI 1.30-1.71) was observed in cancer patients. Conclusion Compared to non-cancer patients, cancer patients have a higher risk of major bleeding but not of re-infarction. Mitigating bleeding risk in STEMI patients with cancer is of paramount importance to improve outcomes.bleeding risk at 1 yearRe-infarction risk at 1 year

Bleeding and Thrombotic Events in Hemodialysis Patients with Atrial Fibrillation on Anticoagulation and Antiplatelet Therapy: A 24-Month Cohort Study

Background and Objectives: Patients undergoing chronic hemodialysis (HD) are predisposed to both thrombotic and bleeding complications due to the complex interplay of end-stage renal disease (ESRD), cardiovascular comorbidities, and the routine use of anticoagulant and antiplatelet therapies. This study aimed to investigate the incidence of bleeding and thrombotic events in chronic HD patients receiving anticoagulant and antiplatelet therapy, with a specific focus on those with atrial fibrillation (AF). Materials and Methods: A total of 224 patients, with 43 (19%) of them diagnosed with AF, were included in this single-center, observational cohort study conducted over 24 months. The cohort was divided into three groups: patients without anticoagulation, those on warfarin monotherapy, and those on combined warfarin and aspirin therapy. Bleeding events were classified as major, clinically relevant non-major bleeding (CRNMB), or minor bleeding, while thrombotic events included ischemic stroke, myocardial infarction, pulmonary embolism, and arteriovenous fistula thrombosis. Results: Overall, 35.7% of patients experienced a bleeding event, with major bleeding occurring in 9.4%. Patients with AF had significantly higher rates of major bleeding (18.6%) compared to those without AF (7.18%; p = 0.043), especially in the combined therapy group. Mortality due to bleeding was also higher in AF patients (14%). In contrast, thrombotic events occurred in 26.8% of patients, with AF patients experiencing significantly more events (48.8%) compared to non-AF patients (21.5%; p = 0.0006). The hazard ratio (HR) for major bleeding in patients on combined warfarin and aspirin therapy was 2.56 (p = 0.016), while the HR for thrombotic events was 2.34 (p = 0.0202). Conclusions: These findings highlight the increased risks of both bleeding and thrombosis in chronic HD patients with AF, particularly those on combined anticoagulation and antiplatelet therapy.

Intracapsular versus extracapsular tonsil surgery: Comparison of postoperative haemorrhage outcomes in the Australasian setting

ObjectiveTo investigate the incidence and timing of postoperative haemorrhage between intracapsular (ICT) and extracapsular tonsillectomy (ECT) techniques and evaluate factors influencing haemorrhage risk and severity. MethodsA retrospective review of patients undergoing tonsillectomy over 5 years across otolaryngology services in Australia and New Zealand. Primary outcomes were rate and timing of post-tonsillectomy haemorrhage. ResultsA total of 12,275 patients were included in this study. The overall post-tonsillectomy bleed rate was 3.3 %, with 0.65 % requiring return to theatre. ICT had a significantly lower bleed rate of 1.7 % compared to 4.1 % for ECT (p < 0.001). The rate of return to theatre was markedly lower for ICT (0.08 %) compared to ECT (0.93 %, p < 0.001). Median day of bleeding was not different between the techniques. Patients undergoing surgery for recurrent tonsillitis had the highest rate of postoperative haemorrhage (15 %), while those with sleep-disordered breathing alone had the lowest (3 %, p < 0.001). ConclusionICT results in significantly lower rates of postoperative haemorrhage and need for surgical intervention compared to ECT. This was most pronounced in paediatric patients with sleep-disordered breathing. ICT may be considered a preferable option for certain patient groups, especially younger children with sleep-disordered breathing, though more evidence is needed to confirm its efficacy and safety in patients with recurrent tonsillitis.

Postoperative Bleeding Risk in Thyroid Surgery: Differences between Conventional and Endoscopic Video-Assisted Neck Surgery Methods.

Postoperative bleeding is a potentially life-threatening complication following thyroidectomy, but the risk factors and timing remain insufficiently understood. The bleeding rate for endoscopic surgery, specifically video-assisted neck surgery (VANS), also remains unclear in Japan. We conducted a retrospective case-control study of postoperative bleeding requiring readmission to the operating room. The overall postoperative bleeding rate was 1.85%. Multivariate analysis revealed that postoperative bleeding was independently associated with antithrombotic therapy (odds ratio 2.95; 95% confidence interval 1.15-7.59) and dialysis (odds ratio 6.53; 95% confidence interval 1.75-24.2). Among patients with postoperative bleeding, the complication developed within 6 h in 56.1% and within 24 h in 93.0%. The postoperative bleeding rate in endoscopic surgery was 1.6%. The most common site of bleeding was around the thyroid in conventional surgery and around the flap in endoscopic surgery. Post-thyroidectomy bleeding is associated with antithrombotic therapy or dialysis. While the bleeding rate in endoscopic surgery is similar to that in conventional surgery, the bleeding site differs.

Study on Engineering Properties and Mechanism of Loess Muck Grouting Materials

Shield tunneling generates a massive amount of muck, and achieving the on-site reuse of muck is an urgent need in the field of shield tunneling. This study, based on a section of the Xianyang diversion tunnel in a loess stratum, aims to optimize the mix ratios of loess muck grouting materials to meet specific performance requirements. Laboratory tests were conducted to analyze the effects of the bentonite content and water–solid ratio on the properties of grout. The engineering properties, cost, and environmental impact of the optimized loess muck grouting materials were compared with those of traditional grouting materials. Additionally, XRD, SEM, and CT were employed to investigate the solidification mechanism of loess muck grouting materials. The results show that the bleeding rate, setting time, fluidity, and consistency of loess muck grouting materials decreased with increasing bentonite content, while these properties increased as the water–solid ratio rose. The compressive strength reached 0.26 MPa and 1.05 MPa at 3 d and 28 d, respectively. Compared to traditional grouting materials, the economic cost and carbon emissions of loess muck grouting materials were reduced by 49.46% and 37.17%, respectively. As the curing time increased, gel filling and particle agglomeration reduced the number of pores. The dense microstructure is the primary factor for the improvement of strength.

Comparison of diagnostic yields, operative times, and post-operative hemorrhage between twist drill versus burr hole craniotomy approaches for stereotactic needle brain biopsy.

Stereotactic frameless needle brain biopsy is a common neurosurgical procedure performed via twist drill or open burr hole approaches. We aim to compare diagnostic yields and surgical outcomes to delineate the safety and efficacy of both approaches. A retrospective database of all stereotactic needle biopsy procedures performed at a single institution over 30 months was conglomerated. Demographics, medical comorbidities, operative details/complications, immediate post-operative imaging, and pathology were abstracted. Two hundred and twenty-five needle biopsies were identified, of which 165 (73.3%) were open, and 60 (26.7%) were twist drill. Diagnostic pathology yield rates between open (84.8%) and twist drill (93.3%) approaches were similar (p = 0.15), with a median of 4 cores taken in each (p = 0.30). Diagnostic tissue yields with an intra-operative pause for pathology confirmation was 90.4% compared to 79.1% without pause (p = 0.036, OR 2.49). Median operative times for open versus twist drill procedures were 68.0min (IQR 49-83) versus 35.5min (IQR 26-54), respectively (Wilcoxon p < 0.001), which remained significant after controlling for awaiting intraoperative pathology using bivariable linear modeling (p < 0.001). Intraoperative bleeding through the needle cannula was noted in 22 patients (9.8%), including eight twist drill (13.3%) and 14 open needles (8.5%). Of 197 cases (87.6%) with post-operative cranial imaging (CT/MRI), 90 (45.7%) demonstrated some degree of post-operative hemorrhage characterized as superficial (n = 10, 11.1%), deep/intralesional (n = 64, 71.1%) bleeding, or both (n = 16, 17.9%). Bleeding rates between open (46.7%) and twist drill (43.3%) approaches were similar (p = 0.78). Post-operative clinical decline or neurological change was noted in 9 patients (4.0%), including one twist drill (1.7%) and eight open needles (4.8%), among which 7 (78%) had deep blood products identified on post-operative imaging. Stereotactic needle biopsy via twist drill approach has similar diagnostic yield rates, asymptomatic bleeding rates, and post-operative complications with significantly shorter operative time and smaller incision size than conventional open burr hole needle biopsy. Using intra-operative frozen histopathology for presumed sufficient diagnostic tissue may improve final pathologic diagnostic rates regardless of approach technique.

Analysis of perinatal outcomes in pregnant women with the resolution of placenta previa in the second trimester

Objective: To investigate perinatal outcomes of pregnant women with the resolution of placenta previa in the second trimester. Methods: This study was a retrospective cohort study, which included singleton pregnant women who received prenatal care and delivered at Peking University Third Hospital from January 1st 2019 to December 31st 2020. A total of 403 pregnant women diagnosed with placenta previa by ultrasound at 20-24 weeks of gestation and the placental position returned to normal before delivery were included in the study group, and 403 pregnant women with normal placental position matched 1∶1 were the control group. The primary outcome was postpartum hemorrhage rate, and secondary outcomes included postpartum bleeding volume, severe hemorrhage complications, blood transfusion, drug application, the application of instrument or surgical hemostasis measures, gestational week of delivery, and neonatal outcomes. The perinatal outcomes were analyzed by univariate and multivariate logistic regression methods. Results: (1) Compared with the control group, the incidence of postpartum hemorrhage [10.4% (42/403) vs 17.6% (71/403)], postpartum hemorrhage volume (median: 375 vs 400 ml), the proportion of postpartum hemorrhage≥500 ml [18.6% (75/403) vs 30.5% (123/403)], and the proportion of application of instrument or surgical hemostasis measures [1.7% (7/403) vs 4.5% (18/403)] in the study group were increased, and the differences were statistically significant (all P<0.05). Neonatal outcomes, including birth weight, small for gestational age, hospitalization in neonatal intensive care unit and incidence of neonatal asphyxia, were compared between the two groups, and there were no statistically significant differences (all P>0.05). (2) In pregnant women with vaginal delivery, the postpartum hemorrhage rate [31.7% (66/208) vs 17.5% (39/223)], postpartum hemorrhage volume (median: 390 vs 380 ml), the proportion of instrument or surgical hemostasis measures [3.8% (8/208) vs 0.4% (1/223)] of the study group were higher than those of the control group, and the differences were statistically significant (all P<0.05). There was no significant difference in the rate of postpartum hemorrhage between the study group and the control group who gave birth by cesarean setion (P=0.545), but the proportion of postpartum hemorrhage≥500 ml in the study group and the control group were 29.2% (57/195) and 20.0% (36/180), and the difference was statistically significant (P=0.039). (3) The results of multivariate analysis showed that compared with the control group, the risk of postpartum hemorrhage (aOR=2.042, 95%CI: 1.313-3.175), the application of drugs (aOR=1.684, 95%CI: 1.142-2.484) and the application of instruments or surgical hemostasis measures (aOR=2.696, 95%CI: 1.089-6.675) were significantly increased in the study group (all P<0.05). Among women who delivered vaginally, the risk of postpartum hemorrhage in the study group was 2.021 times greater than that in the control group (95%CI: 1.269-3.220; P=0.003). Conclusion: In women with placental previa in the second trimester of pregnancy, even if the placental position returns to normal before delivery, it is still a high risk factor for postpartum hemorrhage, especially in vaginal delivery.

Diagnostic value of prenatal ultrasound screening and analysis of pregnancy outcomes in velamentous umbilical cord insertion

Objective: To explore diagnostic value of prenatal ultrasound screening in velamentous umbilical cord insertion (VCI) and its influence on perinatal outcomes, and to provide theoretical basis for clinical practice. Methods: Fifty-eight pregnant women diagnosed with VCI before or after delivery admitted to the First Affiliated Hospital of Xi'an Jiaotong University were selected from January 2012 to December 2022. The clinical features and perinatal outcomes of 45 women finally with VCI after delivery (VCI group) were retrospectively analyzed, and 225 women with normal umbilical cord attachment were selected as the control group during the same period. Results: (1) Among 58 women, 54 (93.1%, 54/58) were diagnosed with VCI by prenatal ultrasound screening, 4 patients (6.9%, 4/58) were missed; and 13 (22.4%, 13/58) were misdiagnosed. Finally, a total of 45 women were confirmed by postpartum placental examination, and 11 (24.4%,11/45) were combined with vasa previa. (2) There were no differences in age, number of pregnancies, and number of induced abortions between the two groups (all P>0.05). Compared with the control group, the rate of assisted reproductive technology [13.3% (6/45) vs 0.4% (1/225); P<0.01], and twin pregnancy rate [8.9% (4/45) vs 0.4% (1/225); P<0.01] in the VCI group were significant higher. (3) Compared with the control group, the rate of placenta previa, succenturiate placenta, vasa previa, postpartum hemorrhage, prenatal hemorrhage and postpartum intrauterine remainder in the VCI group were significant higher (all P<0.05); there was no significant difference in the incidence of placental abruption, premature rupture of membranes, fetal distress and single umbilical artery between the two groups (all P>0.05). The incidence of fetal structural abnormalities in the VCI group (4.4%, 2/45) was higher than that in the control group (1.3%, 3/225), but there was no significant difference between the two groups (P=0.195). (4) The cesarean section rate [75.0% (33/44) vs 45.1% (101/224); P<0.01], preterm birth rate [29.5% (13/44) vs 5.4% (12/224); P<0.01], rate of small for gestational age [20.5% (9/44) vs 5.4% (12/224); P<0.01] in the VCI group were significant higher. However, neonatal birth weight [(2 928±552) vs (3 353±498) g; P<0.01], and 1-minute Apgar score (median: 10 vs 10; P<0.01) in the VCI group were lower than those in the control group. Conclusions: Prenatal ultrasound screening is an important method to diagnose VCI. VCI is more prone to adverse pregnancy outcomes, such as postpartum hemorrhage, premature delivery, small for gestational age, et al. Its risk factors include twin pregnancy, assisted reproductive technology, placenta previa, and para-placenta.

A double‐blind, randomized, placebo‐controlled trial of melatonin as an adjuvant agent for induction of labor: The MILO trial

AbstractIntroductionMelatonin has been suggested to have a biological role in the onset and progress of labor. We tested the hypothesis that the addition of melatonin during an induction of labor will reduce the need for a cesarean birth.Material and MethodsThis trial underwent protocol amendments that are detailed in the main text of the article. This trial is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12616000311459). At a multi‐center health service including secondary and tertiary obstetric hospitals, we performed a randomized, double‐blind, placebo‐controlled trial in women with a singleton cephalic pregnancy, free of significant maternal or perinatal complications who were undergoing induction of labor (with or without cervical ripening). Women were randomized to 10 mg melatonin vs placebo, with cervical ripening as required, and then 6‐h during their induction of labor to a maximum of four doses or until birth. The primary outcome was cesarean birth. Secondary outcomes included labor, maternal, and neonatal outcomes. Data were analyzed using intention to treat. Sub‐group analyses based on mode of ripening and parity were also performed.ResultsBetween 2019 and 2021 we randomized 189 women (103 to melatonin and 86 to placebo). The study was prematurely terminated due to logistical complications resulting from the COVID‐19 pandemic. Cesarean rates were 28/103 (27.2%) in the melatonin group versus 20/84 (23.3%) in the placebo group (RR 1.17 95% CI 0.71–1.92). There were no significant differences in rate of cesarean birth between the melatonin and placebo groups for failure to progress (13.4% and 9.3%, respectively, RR 1.46; 95% CI 0.64–3.32) or suspected fetal distress (10.7% and 10.5%, respectively, RR 1.02; 95% CI 0.44–2.34). The melatonin group had significantly lower rates of spontaneous vaginal birth within 24 h (35.0% vs. 50.0%; RR 0.70 95% CI 0.50–0.98). The rates of secondary outcomes such as total length of labor, rate of postpartum hemorrhage, and instrumental birth were comparable. Babies born in the melatonin group were more likely to need admission to the special care nursery, namely for hypoglycemic monitoring (18.5% vs. 8.1% RR 2.26; 95% CI 1.00–5.10).ConclusionsIn women undergoing induction of labor, melatonin does not reduce the cesarean section rate. Melatonin use intrapartum may also be associated with neonatal hypoglycemia.