Relative Risk Of Bleeding Research Articles

Meta-Analysis Comparing Oral Anticoagulant Monotherapy Versus Dual Antithrombotic Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease.

Oral anticoagulants (OACs) are routinely used for the management of atrial fibrillation (AF) while antiplatelet agents are used in coronary artery disease (CAD). However, data regarding the comparative clinical outcomes of OAC monotherapy versus dual antithrombotic therapy (anticoagulant plus antiplatelet agent) in patients with AF and stable CAD are limited. A comprehensive search of major databases including PubMed/MEDLINE, Cochrane Library, and Embase was performed from inception to September 1, 2024 to identify randomized control trials (RCTs) that compared OAC monotherapy with dual antithrombotic therapy in patients with AF and stable CAD. The risk ratios (RRs) were estimated with corresponding 95% confidence intervals (CIs) for all outcomes. A total of three RCTs reported data for 3945 patients with AF and stable CAD. The mean age of patients was 73.8 (±11.85) years and the mean follow-up was 22 months. OAC monotherapy was associated with a significantly reduced relative risk of major bleeding (RR: 0.55, 95% CI: 0.32-0.95) compared to dual therapy. The risk of all-cause death (RR: 0.85, 95% CI: 0.49-1.48), cardiovascular death (RR: 0.84, 95% CI: 0.50-1.41), any stroke event (RR: 0.74, 95% CI: 0.46-1.18), and myocardial infarction (RR: 1.57, 95% CI: 0.79-3.12) remained comparable across the two groups. OAC monotherapy led to a significant relative risk reduction for major bleeding with similar rates of ischemic events and mortality compared to dual antithrombotic therapy in patients with AF and stable CAD.

Association of caesarean scar defect with risk of abnormal uterine bleeding: results from meta-analysis

ObjectiveTo investigate the association between caesarean scar defects and abnormal uterine bleeding through systematic literature review.MethodsPubMed, Web of Science, Cochrane Library and Embase databases were searched based on PRISMA 2020 to include studies exploring abnormal uterine bleeding in women with caesarean scar defects. The combined relative risk (RR) of uterine bleeding, combined prevalence of abnormal uterine bleeding and combined RR of intermenstrual uterine bleeding were calculated using a fixed- or random-effects model.ResultsTen studies involving 1,183 women with caesarean scar defects met the inclusion criteria for this study. Compared with women without caesarean scar defects, those with caesarean scar defects had a higher risk of abnormal uterine bleeding (RR: 3.22, 95% CI: 1.83–5.66) and intermenstrual bleeding (RR: 2.93, 95% CI: 1.91–4.50). The prevalence of abnormal uterine bleeding was approximately 0.46 (95% CI: 0.27–0.64), and across populations, women with a previous caesarean section who had undergone imaging specifically for gynaecological disease had a significantly higher prevalence of abnormal uterine bleeding (0.77, 95% CI: 0.65–0.89) than those with at least one caesarean Sect. (0.25, 95% CI: 0.10–0.39).ConclusionA significant association was observed between caesarean scar defects and abnormal uterine bleeding, with the former being a risk factor for the latter. However, previous studies have differed in the definition of caesarean scar defects and abnormal uterine bleeding, and more high-quality studies are needed to further investigate the relevant definitions and study results in the future.

Efficacy and safety of oral anticoagulants according to kidney function among patients with atrial fibrillation.

Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function. Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding. Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49mL/min/1.73m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49mL/min/1.73m2. Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30mL/min/1.73m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49mL/min/1.73m2.

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.

Machine learning model for predicting physical activity related bleeding risk in Chinese boys with haemophilia A

BackgroundPhysical activity is a crucial part of an active lifestyle for haemophiliac children. However, the fear of bleeds has been identified as barriers to participating physical activity for haemophiliac children even with prophylaxis. Lack of evidence and metrics driven by data is key problem. ObjectivesWe aim to develop machine learning models based on clinical data with multiple potential factors considered to predict risk of physical activity bleeding for haemophilia children with prophylaxis. MethodsFrom this cohort study, we collected information on 98 haemophiliac children with adequate prophylaxis (trough FVIII:C level > 1 %). The involved potential predictor variables include demographic information, treatment information, physical activity, joint evaluation, and pharmacokinetic parameters, etc. We applied CoxPH, Random Survival Forests (RSF) and DeepSurv to construct prediction models for the risk of bleeding during physical activities. All three survival analysis models were internally and externally validated. ResultsA total of 98 patients were enrolled in this study. Their median age was 7.9 (5.5, 10.2) years. The CoxPH, RSF and DeepSurv models' discriminative and calibration abilities were all high, and the RSF model had the best performance (Internal validation: C-index, 0.7648 ± 0.0139; Brier Score, 0.1098 ± 0.0015; External validation: C-index, 0.7260 ± 0.0154; Brier Score, 0.0930 ± 0.0018). The prediction curves demonstrated that the developed RSF model can distinguish the risks well between bleeding and non-bleeding patients, as well as patients with different levels of physical activity. Meanwhile, the feature importance analysis confirmed that physical activity bleeding was deduced by comprehensive effects of various factors, and the importance of different factors on bleeding outcome is discrepant. ConclusionsThis study revealed from the mechanism that it is necessary to incorporate multiple factors to accurately predict physical activity related bleeding risk. In clinical practice, the designed machine learning models can provide guidance for children with haemophilia A to positively participate in physical activity.

Comparison of Antiplatelet Monotherapies After Percutaneous Coronary Intervention According to Clinical, Ischemic, and Bleeding Risks

BackgroundClopidogrel was superior to aspirin monotherapy in secondary prevention after percutaneous coronary intervention (PCI). ObjectivesThe purpose of this study was to evaluate the benefits of clopidogrel across high-risk subgroups MethodsThis was a post hoc analysis of the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of coronary artery diseases-EXtended Antiplatelet Monotherapy) trial that randomly assigned patients who were event free for 6 to 18 months post-PCI on dual antiplatelet therapy (DAPT) to clopidogrel or aspirin monotherapy. Two clinical risk scores were used for risk stratification: the DAPT score and the Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention (TRS 2°P) (the sum of age ≥75 years, diabetes, hypertension, current smoking, peripheral artery disease, stroke, coronary artery bypass grafting, heart failure, and renal dysfunction). The primary composite endpoint was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission because of acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type ≥3) at 2 years after randomization. ResultsAmong 5,403 patients, clopidogrel monotherapy showed a lower rate of the primary composite endpoint than aspirin monotherapy (HR: 0.73; 95% CI: 0.59-0.90). The benefit of clopidogrel over aspirin was consistent regardless of TRS 2°P (high TRS 2°P [≥3] group: HR: 0.65 [95% CI: 0.44-0.96]; and low TRS 2°P [<3] group: HR: 0.77 [95% CI: 0.60-0.99]) (P for interaction = 0.454) and regardless of DAPT score (high DAPT score [≥2] group: HR: 0.68 [95% CI: 0.46-1.00]; and low DAPT score [<2] group: HR: 0.75 [95% CI: 0.59-0.96]) (P for interaction = 0.662). The association was similar for the individual outcomes. ConclusionsThe beneficial effect of clopidogrel over aspirin monotherapy was consistent regardless of clinical risk or relative ischemic and bleeding risks compared with aspirin monotherapy. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis- EXtended Antiplatelet Monotherapy [HOST-EXAM]; NCT02044250)

Selective serotonin reuptake inhibitors related bleeding risk: case report and review of literature

Gastrointestinal bleedings are relevant side effects in patients during anticoagulant therapy for atrial fibrillation. Direct oral anticoagulants (DOACs) are less correlated with major bleeding events than vitamin K antagonists (VKAs), but concerns are present about the relative risk of gastrointestinal bleeding. Here we report the case of a patient with atrial fibrillation and dementia on DOAC treatment who developed a SSRI-associated thrombocytopenia with subsequent life-threatening bleeding. Physicians should be aware of the possible correlation between SSRI-induced thrombocytopenia and concomitant use of anticoagulant and/or antiplatelet drugs, thus preventing life-threatening bleedings.

Mortality and bleeding associated with the management of sub-massive pulmonary embolism: a systematic review and Bayesian network meta-analysis

Current guidelines recommend anticoagulation (AC) for low and intermediate-risk pulmonary embolism (PE) and systemic thrombolysis (tPA) for high risk (massive) PE. How these treatment options compare with other modalities of treatment such as catheter directed thrombolysis (CDT), ultrasound assisted catheter thrombolysis (USAT), and administering lower dose of thrombolytics (LDT) is unclear. There is no study that has compared all these treatment options. We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials in patients with submassive (intermediate risk) PE. Fourteen randomized controlled trials were included, comprising 2132 patients. On Bayesian network meta-analysis, a significant decrease in mortality was noted in tPA versus AC. There was no significant difference between USAT versus CDT. For risk of major bleeding, there was no significant difference in relative risk of major bleeding between tPA versus AC and USAT versus CDT. tPA was found to have a significantly higher risk of minor bleeding and a lower risk of recurrent PE compared to AC. Systemic thrombolysis is associated with a significant reduction in mortality and recurrent PE compared to anticoagulation but an increased risk of minor bleeding. There was no difference in risk of major bleeding. Our study also shows that while the newer modalities of treatment for pulmonary embolism are promising, there is lack of data to comment on the purported advantages.

Contemporary Antiplatelet and Anticoagulant Therapies for Secondary Stroke Prevention: A Narrative Review of Current Literature and Guidelines.

Stroke is a leading cause of death and disability worldwide. The annual incidence of new or recurrent stroke is approximately 795,000 cases per year in the United States, of which 87% are ischemic in nature. In addition to the management of modifiable high-risk factors to reduce the risk of recurrent stroke, antithrombotic agents (antiplatelets and anticoagulants) play an important role in secondary stroke prevention. This review will discuss the published literature on the use of antiplatelets and anticoagulants in secondary prevention of acute ischemic stroke and transient ischemic attack (TIA), including their pharmacology, efficacy, and adverse effects. We will also highlight the role of dual antiplatelet therapy (DAPT) in secondary stroke prevention, along with supporting literature. Single antiplatelet therapy (SAPT) with aspirin or clopidogrel reduces the risk of recurrent ischemic stroke in patients with non-cardioembolic ischemic stroke or TIA. However, as shown in recent trials, short-term DAPT with aspirin and clopidogrel or ticagrelor for 21-30days is more effective than SAPT in patients with minor acute non-cardioembolic stroke or high-risk TIA. Although short-term DAPT is highly effective in preventing recurrent stroke, a more prolonged course can increase bleeding risks without additional benefit. DAPT for 90days, followed by aspirin monotherapy for patients with large vessel intracranial atherosclerotic disease, is suitable for secondary stroke prevention. However, patients need to be monitored for both minor (e.g., bruising) and major (e.g., intracranial) bleeding complications. Conversely, oral warfarin and newer direct oral anticoagulant (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban are the agents of choice for secondary stroke prevention in patients with non-valvular cardioembolic strokes. DOACs may be preferred over warfarin due to decreased bleeding risks, including ICH, lack of need for international normalized ratio monitoring, no dietary restrictions, and limited drug-drug interactions. The choice between different antiplatelets and anticoagulants for prevention of ischemic stroke depends on the underlying stroke mechanism, cytochrome P450 2C19 polymorphisms, bleeding risk profile, compliance, drug tolerance, and drug resistance. Physicians must carefully weigh each patient's relative benefits and bleeding risks before initiating an antiplatelet/anticoagulant treatment regimen. Further studies are warranted to study the optimal duration of DAPT in symptomatic intracranial atherosclerosis since the benefit is most pronounced in the short term while the bleeding risk remains high during the extended duration of therapy.

Safety of Transbronchial Biopsies in Patients with Pulmonary Hypertension: Systematic Review and Meta-Analysis.

Rationale: Transbronchial lung biopsies (TBLBs) are commonly performed by pulmonologists. Most providers consider pulmonary hypertension to be at least a relative contraindication to TBLB. This practice is based primarily on expert opinion, as there are very few patient outcomes data backing it. Objectives: We performed a systematic review and meta-analysis of previously published studies to determine the safety of TBLB in patients with pulmonary hypertension. Methods: The MEDLINE, Embase, Scopus, and Google Scholar databases were searched for pertinent studies. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using MedCalc version 20.118 to calculate the weighted pooled relative risk of complications in patients with pulmonary hypertension. Results: Nine studies with a total of 1,699 patients were included in the meta-analysis. On the basis of the Newcastle-Ottawa Scale, the risk of bias was low in the included studies. The overall weighted relative risk of bleeding with TBLB in patients with pulmonary hypertension was 1.01 (95% confidence interval, 0.71-1.45) compared with patients without pulmonary hypertension. Heterogeneity was low; therefore, the fixed-effects model was used. In a subgroup analysis of three studies, the overall weighted relative risk of significant hypoxia in patients with pulmonary hypertension was 2.06 (95% confidence interval, 1.12-3.76). Conclusions: Our results show that the patients with pulmonary hypertension do not have a significantly elevated risk of bleeding with TBLB compared with control subjects. We hypothesize that significant postbiopsy bleeding might be preferentially originating from bronchial artery circulation as opposed to pulmonary artery circulation, much like episodes of massive spontaneous hemoptysis. This hypothesis can explain our results, as in this scenario, elevated pulmonary arterial pressure would not be expected to have a bearing on the risk of post-TBLB bleeding. Most of the studies in our analysis included patients with mild to moderate pulmonary hypertension and it is not clear if our results can be extrapolated to patients with severe pulmonary hypertension. We noted that the patients with pulmonary hypertension were at a higher risk of developing hypoxia and needing a longer duration of mechanical ventilation with TBLB compared with control subjects. Further studies are needed to better understand the origin and pathophysiology of post-TBLB bleeding.

Prasugrel-based de-escalation vs. conventional therapy after percutaneous coronary intervention in ACS patients according to the renal function

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): A consortium of six companies in Korea (Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Qualitech Korea, and Dio). Background Patients with coronary artery disease and impaired renal function are at higher risk for both bleeding and ischemic adverse events after percutaneous coronary intervention (PCI). Purpose We assessed the efficacy and safety of a prasugrel based de-escalation strategy in patients with impaired renal function. Methods We conducted a post-hoc analysis of the HOST-REDUCE-POLYTECH-ACS study. Patients with available estimated glomerular filtration rate (eGFR) (n=2,311) were categorized into three groups. (high eGFR: ≥90 mL/min; intermediate eGFR: ≥60 and &amp;lt;90 mL/min; low eGFR: &amp;lt;60 mL/min). The endpoints were bleeding outcomes (Bleeding Academic Research Consortium type 2, or higher), ischemic outcomes (cardiovascular death, myocardial infarction, stent thrombosis, repeat revascularization, and ischemic stroke), and net adverse clinical events (all cause death, BARC 2 or greater bleeding, MI, stent thrombosis, repeat revascularization, and ischemic stroke) at 1 year follow-up. The hazard ratio (HR) and 95% Confidence interval (CI) were calculated from the multivariate Cox proportional hazard regression analysis. Covariates that were considered clinically meaningful were included. The probability risk ratio was obtained by dividing ischemic hazard function from the bleeding hazard function. Results With respect to net adverse clinical events, prasugrel de-escalation was beneficial regardless of baseline renal function (p for interaction = 0.508). The relative reduction in bleeding risk from prasugrel de-escalation was higher in the low eGFR group compared with that from both the intermediate and high eGFR groups (relative reduction: 64% [HR 0.36, 95% CI 0.15–0.83] vs. 50% [HR 0.50, 95% CI 0.28-0.90] and 52% [HR 0.48, 95% CI 0.21-1.13] for low, intermediate, and high eGFR groups, p for interaction=0.646). Ischemic risk from prasgurel de-escalation was not significant in all eGFR groups ([HR 1.18, 95% CI 0.47-2.98], [HR 0.95, 95% CI 0.53-1.69], and [HR 0.61, 95% CI 0.26-1.39)], respectively, p for interaction=0.119). The probability risk ratio was highest in low eGFR group (1.06 vs. 1.26 vs. 1.36, for high, intermediate, and low eGFR groups, respectively, p for trend&amp;lt;0.001), suggesting higher relative bleeding risk above ischemic risk. Within those randomized to the de-escalation strategy, the mean probability risk ratio was not significantly different according to renal function (0.89, vs. 0.84 vs. 0.80 respectively, p for trend = 0.053), which was in contrast to those randomized to the conventional strategy where the mean probability risk ratio increased significantly as renal function decreased (1.24 vs. 1.67 vs. 1.94 respectively, p for trend&amp;lt;0.001). Conclusion The beneficial effect of prasugrel-based de-escalation strategy was consistent regardless of the baseline renal function, which was mostly driven by a reduction in bleeding risk which was greatest in those with low eGFR.

The relative risk of bleeding after medical hospitalization: the medical inpatient thrombosis and hemorrhage study

BackgroundClinically relevant bleeding risk in discharged medical patients is underestimated and leads to rehospitalization, morbidity, and mortality. Studies assessing this risk are lacking. ObjectiveThe aim of this study was to develop and validate a computable phenotype for clinically relevant bleeding using electronic health record (EHR) data and quantify the relative and absolute risks of this bleeding after medical hospitalization. MethodsWe conducted an observational cohort study of people receiving their primary care at sites affiliated with an academic medical center in northwest Vermont, United States. We developed a computable phenotype using EHR data (diagnosis codes, procedure codes, laboratory, and transfusion data) and validated it by manual chart review. Cox proportional hazard models with hospitalization modeled as a time-varying covariate were used to estimate clinically relevant bleeding risk. ResultsThe computable phenotype had a positive predictive value of 80% and a negative predictive value of 99%. The bleeding rate in individuals with no medical hospitalizations in the past 3 months was 2.9 per 1000 person-years versus 98.9 per 1000 person-years in those who were discharged in the past 3 months. This translates into a hazard ratio (95% CI) of clinically relevant bleeding of 22.9 (18.9, 27.7), 13.0 (10.0, 16.9), and 6.8 (4.7, 9.8) over the first, second, and third months after discharge, respectively. ConclusionWe developed and validated a computable phenotype for clinically relevant bleeding and determined its relative and absolute risk in the 3 months after medical hospitalization discharge. The high rates of bleeding observed underscore the clinical importance of capturing and further studying bleeding after medical discharge.

EVALUATION OF LOWER GASTROINTESTINAL BLEEDING RISK ASSOCIATED WITH USE OF LOW DOSE ASPIRIN

To evaluate risk of aspirin related lower gastrointestinal bleeding a Prospective study was performed at Department of medicine, Nishtar Hospital, Multan from July 2019 to January 2020. Total 372 patients using low dose aspirin were selected from out-patient department of Medicine. All patients underwent diagnostic laboratory test for stool examination. A consultant pathologist confirmed presence or absence of lower gastrointestinal bleeding. Data including age, gender, history of bleeding per rectum, blood on stools, BMI, duration of aspirin use, and reason for aspirin prescription was recorded. The study was conducted on 372 patients, 120 (32.3%) were female while 252 (67.7 %) were male. Mean age of the patients was 40 years. Mean duration of use of low dose aspirin was 22.23 ± 16.59 months. Lower gastrointestinal bleeding was noted in 81 (21.8%). Use of dose aspirin is significantly associated with lower gastrointestinal bleeding. Clinicians must anticipate adverse effects in such patients.

Abstract 13175: The Effect of Impella Placement on Morbidity and Mortality in Cardiogenic Shockcomparing Outcomes of Two Percutaneous Mechanical Circulatory Support Modalities as Bridges to Advanced Heart Failure Therapy

Objectives: The use of percutaneous mechanical circulatory support (PMCS) devices offers a means to maintain hemodynamic stability in pre-transplant patients. The Impella Heart Pump and the intra-aortic balloon pump (IABP) are two devices commonly employed for this purpose. We sought to compare the relative safety and efficacy of Impella vs IABP using a retrospective cohort of patients at our institution from 2014-2021. Methods: 239 patients received Impella support, and 220 patients received IABP. Of these patients, 26 receiving Impella and 49 receiving IABP were identified as pre-transplant/VAD. The incidences of 30-day mortality, major bleeding, hemolysis, limb ischemia, stroke, repositioning, and infection were recorded. The number of patients receiving transplants, VADs, Mechanical Circulatory Support escalation, and ECMO were also recorded. The relative risks of complications were calculated, and an alpha of 0.05 was assigned to identify significance. Results: The average age of the IABP group was 54.8 +/- 12.1 years with 39 males to 10 females. The average age of the Impella group was 44.8 +/- 15 years with 15 males to 11 females. There was no significant difference in pre-placement EF between these two groups (IABP EF = 19.28+/-8.62, Impella EF = 21.15+/-9.69; p = 0.4016). A significantly higher relative risk of mortality (RR = 3.23; 95% CI = 1.45-7.20, p = 0.0041), major bleeding (RR = 8.48; 95% CI = 3.2 - 22.45, p &lt; 0.00001), and hemolysis (RR = 35.2; 95% CI = 2.12-582, p = 0.0128) was noted in patients receiving Impella support. No significant difference in the incidence of limb ischemia, stroke, repositioning, or infection was observed between these two groups. A significantly higher number of patients receiving Impella support also required ECMO (p = 0.0003) Conclusions: These data suggest that a higher risk of mortality or major complications may exist for patients receiving Impella support pre-transplant/VAD. Further analysis is needed to correct for baseline differences between these two cohorts.

Effectiveness and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: a nationwide registry-based study.

To compare the effectiveness and safety of clopidogrel, ticagrelor, and prasugrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Nationwide, registry-based study of STEMI patients treated with primary PCI (2011-17) and subsequently with aspirin and a P2Y12 inhibitor. The effectiveness outcome was major adverse cardiovascular events (MACE) defined as a composite of recurrent myocardial infarction, repeat revascularization, stroke, or cardiovascular death at 12 months. The safety outcome was bleeding requiring hospitalization at 12 months. Multivariable logistic regression with average treatment effect modeling was used to calculate absolute and relative risks for outcomes standardized to the distributions of demographic characteristics of all included subjects. We included 10 832 patients; 1 697 were treated with clopidogrel, 7 508 with ticagrelor, and 1,627 with prasugrel. Median ages were 66, 63, and 59 years (P < 0.001). Standardized relative risks of MACE were 0.75 for ticagrelor vs. clopidogrel (95% confidence interval [CI], 0.64-0.83), 0.84 for prasugrel vs. clopidogrel (95% CI, 0.73-0.94), and 1.12 for prasugrel vs. ticagrelor (95% CI, 1.00-1.24). Standardized relative risks of bleeding were 0.77 for ticagrelor vs. clopidogrel (95% CI, 0.59-0.93), 0.89 for prasugrel vs. clopidogrel (95% CI, 0.64-1.15), and 1.17 for prasugrel vs. ticagrelor (95% CI, 0.89-1.45). Ticagrelor and prasugrel were associated with lower risks of MACE after STEMI than clopidogrel, and ticagrelor was associated with a marginal reduction compared with prasugrel. The risk of bleeding was lower with ticagrelor compared with clopidogrel, but did not significantly differ between ticagrelor and prasugrel.

Impact of Ticagrelor Versus Clopidogrel on Bleeding Outcomes of Isolated Coronary Artery Bypass Grafting

BackgroundIncreased bleeding risks have been documented in patients exposed to P2Y12 inhibitors within 5 days of coronary artery bypass surgery (CABG). This study aimed to determine the relative CABG bleeding risks of clopidogrel versus ticagrelor exposure and the proper time course of ticagrelor discontinuation prior to surgery. MethodsClinical outcomes were assessed in 2075 isolated CABG patients, including 375 who had received P2Y12 inhibitors within 5 days of surgery (155 clopidogrel, 213 ticagrelor, 7 prasugrel). BARC-4 CABG bleeding complications and perioperative blood product usage were assessed in propensity-matched P2Y12-inhibited and non-P2Y12-inhibited cohorts. ResultsP2Y12-inhibited patients (n = 375) in comparison to matched non-P2Y12-inhibited patients (n = 1138) had higher rates of re-operation for bleeding (3.8 % vs 1.3 %, p = 0.003), postoperative red blood cell transfusion ≥5 units (5.7 % vs 2.7 %, p = 0.007), and intraoperative and postoperative blood product utilization (42.3 % vs 27.1 %, p < 0.001; 41.8 % vs 32.2 %, p < 0.001, respectively). Univariate predictors of BARC-4 bleeding included clopidogrel (OR: 2.145, 95 % CI: 1.131–4.067, p = 0.019) and ticagrelor discontinued within 3 days of surgery (OR: 2.153, 95 % CI: 1.003–4.169, p = 0.049). Multivariate logistic regression demonstrated that only clopidogrel exposure was an independent BARC-4 bleeding predictor (OR: 1.850, 95 % CI: 1.007–3.398, p = 0.048). Unadjusted ticagrelor patients with drug discontinuation 4–5 days prior to CABG only demonstrated higher rates of perioperative platelet transfusion, without additional signs of excessive bleeding. ConclusionsClopidogrel exposure within 5 days of CABG is an independent predictor of BARC-4 bleeding, whereas major ticagrelor bleeding effects are confined to drug exposure within 3 days of surgery.

Thromboprophylaxis in Urological and Andrological Surgery (Review article)

Last decades urologist started to performed big amount of complicated oncological operation with substantial risk of both venous thromboembolism (VTE) and bleeding. Prophylaxis of VTE remains a vital problem, as it is potentially fatal and is associated with significant morbidity. Prophylaxis of this complication is not clearly defined and is mainly based on information from other surgical specialties (like orthopedic or general surgery). Scientific publications dedicated VTE prophylaxis in field of urology were reported only in the last decade. Most studies showed that pharmacological prophylaxis decreases the relative risk of VTE in surgical patients by approximately 50%, but with an increase in the relative risk of postoperative major bleeding of 50%. Main models for evaluation of different VTE risk factors were analyzed. The most important risk factors for VTE are age of 75 or more, body mass index 35 or more, prior VTE or VTE in 1st degree relative. As for urological procedure, deep venous thrombosis rates of 0.2–7.8% and pulmonary embolism of 0.2–7% have been reported. It was shown that recommendations for VTE prophylaxis varies in different guidelines and their summary for most popular operations were described. Generally, most recommendations state that low-risk procedures need no prophylaxis or solely mechanical prophylaxis. Moderate-risk categories can either have mechanical or pharmacological prophylaxis. The high-risk category should have both mechanical and pharmacological prophylaxis, and extended prophylaxis should be considered. Despite massive evidences about risk of VTE among different types of surgical patients, real clinical practice doesn’t show the strict adherence to VTE prophylaxis recommendations.

Association of Antisecretory Drugs with Upper Gastrointestinal Bleeding in Patients Using Oral Anticoagulants: A Systematic Review and Meta-Analysis

BackgroundThe role of antisecretory drugs for the prevention of upper gastrointestinal bleeding in patients using anticoagulants is unclear. We investigated this question in a systematic review and meta-analysis. MethodsWe searched Embase, PubMed, Web of Science, Scopus, the Cochrane Library, and clinicaltrials.gov thru April 2021 for controlled randomized trials and observational studies evaluating the association of proton pump inhibitors (PPIs) or H2-receptor antagonists with overt upper gastrointestinal bleeding in patients using anticoagulants. Independent duplicate review, data extraction, and risk of bias assessment were performed. Observational studies were included only if they provided results controlled for at least 2 variables. Meta-analyses were performed using random effects models. ResultsSix observational studies and 1 randomized trial were included. All but 1 study had low risk of bias. None of the studies excluded patients with concomitant aspirin or nonsteroidal anti-inflammatory drug use. For PPIs, the pooled relative risk of upper gastrointestinal bleeding was 0.67 (95% confidence interval 0.61, 0.74) with low statistical heterogeneity (I2 = 15%). Individual studies showed greater treatment effect in patients with higher risk for upper gastrointestinal bleeding (eg, nonsteroidal anti-inflammatory drug or aspirin use, elevated bleeding risk score). A single observational study evaluating the association of H2-receptor antagonists with upper gastrointestinal bleeding found a relative risk of 0.69 (95% confidence interval 0.24-2.02). ConclusionsEvidence drawn mostly from observational studies with low risk of bias demonstrate that PPIs reduce upper gastrointestinal bleeding in patients prescribed oral anticoagulants. The benefit appears to be most clearcut and substantial in patients with elevated risk of upper gastrointestinal bleeding.

The risks of thrombotic and bleeding events in patients receiving PEGylated asparaginase for treatment of acute lymphoblastic leukemia.

e19015 Background: The prognosis of adult patients with acute lymphoblastic leukemia (ALL) has improved with the adoption of pediatric-inspired chemotherapy regimens. PEGylated asparaginase (PEG-Asp) is essential to these regimens. Although PEG-Asp is associated with an increased risk of coagulopathy, venous thromboembolism, and depletion of antithrombin III (AT3), there is limited data evaluating the risk of thrombosis and bleeding and optimal antithrombotic interventions in these patients are unknown. Methods: We performed a single-center retrospective study of patients ≥ 18 years-old who received PEG-Asp for B- or T-ALL at the University of Virginia between 2015 and 2020. The primary outcomes were the incidence of thrombosis and bleeding events. All patients received prophylactic AT3 repletion for activity level &lt;60% &amp; cryoprecipitate for fibrinogen &lt;100mg/dL. None received prophylactic anticoagulation. All received prednisone during induction at a median daily dose of 1 mg/kg. Results: We identified 57 patients who received PEG-Asp for ALL. Median age was 32 years (range 18-63). Five patients (8.8%) had a thrombotic event during induction versus five (16%) during post-induction. Four patients (7%) had a bleeding event during induction versus five (10%) during post-induction. The most common type of thrombosis was deep venous thrombosis, with the majority being catheter-associated. Pulmonary embolism and CNS thrombosis were less common. During induction, the median time to thrombotic event was 18 days after last PEG-Asp administration. 60% and 80% of patients received AT3 and cryoprecipitate, respectively. During post-induction, the median time to thrombotic event was 58 days after last PEG-Asp administration. 38% and 63% of the patients received AT3 and cryoprecipitate, respectively. There was one episode of major bleeding during induction and six during post-induction. Conclusions: Though the increase in thrombotic risk in adult patients receiving PEG-Asp is well-characterized, rates of reported thromboses vary widely. Studies examining bleeding risk associated with PEG-Asp regimens are even scarcer and with variable outcomes. There was a significant occurrence of both thrombotic and bleeding events associated with administration of PEG-Asp. More investigation into the relative thrombotic and bleeding risks associated with PEG-Asp is needed to determine optimal antithrombotic interventions in adult patients with ALL.[Table: see text]

Access site bleeding complications comparing oral anticoagulation therapy with NOACs and VKAs in patients with atrial fibrillation undergoing cardiac implantable device intervention

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation is frequent in patients undergoing cardiac implantable electronic device (CIED) intervention. Such population require oral anticoagulation therapy, which increases risk of procedure related bleeding. There is a lack on data on procedure-related bleeding outcome with non-vitamin K antagonist anticoagulants (NOACs) vs vitamin K antagonist anticoagulants (VKAs) in patients with AF undergoing CIED intervention. Study purpose Aim of the present stud was to evaluate whether NOACs have a safety benefit compared to VKAs in terms of fewer hemorrhagic complications at the site of CIED implant. Methods Consecutive AF patients receiving NOACs or VKAs at the time of CIED procedure were included in this observational, retrospective, monocentric investigation. Primary endpoint was the incidence of post-intervention clinically significant pocket hematoma. Multivariate analysis was performed to investigate the association between covariates and the primary endpoint. Results A total of 311 patients were enrolled, 146 on NOACs and 165 on VKAs. The incidence of pocket hematoma was 3.4% in the NOAC vs 13.3% in the VKA group (p=0.002) (Figure 1). Primary outcome-free survival at 30-days was 96.6 % in patients on NOACs and 86.0% in those on VKAs (p=0.019) (Figure 2). Multivariate analysis, adjusted by propensity-score calculation of inverse-probability-weighting, showed a significantly lower occurrence of pocket hematoma in patients receiving NOACs vs VKAs (HR 0.35, 95% CI 0.13-0.96, p=0.042). Such NOACs benefit was confirmed vs patients on VKAs without peri-procedural bridging with low-molecular weight heparin (HR 0.34, 95% CI 0.11-0.99, p=0.048). The incidence of pocket infection, surgical pocket evacuation, ischemic events and major bleeding complications at 30 days (secondary endpoints) was similar in the two groups. Conclusion Among patients with AF undergoing implantable cardiac defibrillator or pace-maker intervention, the use of NOACs vs VKAs is associated with significant reduction of post-procedural pocket hematoma, regardless of bridging with low molecular-weight heparin in the VKA group.