Major Bleeding In Patients Research Articles

Pharmacokinetic and Pharmacogenetic Predictors of Major Bleeding Events in Patients with an Acute Coronary Syndrome and Atrial Fibrillation Receiving Combined Antithrombotic Therapy.

Objective: This study's objective was to evaluate the effects of pharmacokinetic and pharmacogenetic factors on major bleeding in patients with ACS and non-valvular AF receiving combined antithrombotic therapy consisting of rivaroxaban, clopidogrel, and aspirin as part of dual or triple therapy. Methods: A prospective observational study was conducted in two PCI centers in Moscow, the Russian Federation, from 2017 to 2018. One hundred patients with ACS and AF were enrolled. Prospective follow-ups continued for 12 months. Results: A total of 36 patients experienced bleeding events, with 10 experiencing major bleeding based on the BARC scale and 17 experiencing major bleeding based on the ISTH scale. The following predictors associated with an increased number of major bleeding events were identified: for the ISTH scale, a Css min. of rivaroxaban of >137 pg/mL (5.94 OR, (95% CI, 3.13-12.99; p < 0.004)) and carriage of the T allelic variant polymorphism ABCB1 rs4148738 (8.97 OR (95% CI, 1.48-14.49; p < 0.017)), as well as for the BARC scale (5.76 OR (95% CI, 2.36-9.87; p < 0.018)). Conclusions: Measuring residual steady-state rivaroxaban concentrations and determining the carriage of the T allelic variant polymorphism ABCB1 rs4148738 may be applicable to high-risk patients for subsequent antithrombotic therapy modification.

In hospitalized patients undergoing therapeutic plasma exchange, major bleeding prevalence depends on the bleeding definition: An analysis of The Recipient Epidemiology and Donor Evaluation Study-III.

Major bleeding in patients undergoing therapeutic plasma exchange (TPE) has been studied in large databases; but without standardizing bleeding definitions. Therefore, we used standardized definitions to evaluate major bleeding in hospitalized patients undergoing TPE using public use data files from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). In a retrospective cross-sectional analysis, we identified TPE-treated adults in a first inpatient encounter. We evaluated major bleeding prevalence using (1) International Classification of Diseases (ICD) or Current Procedural Terminology (CPT) codes, (2) packed red blood cell (PRBC) transfusion, or (3) hemoglobin (Hgb) decline. Patients with major bleeding prior to their first TPE were excluded from the analysis. Among 779 patients undergoing TPE, major bleeding by at least one of the three bleeding definitions occurred in 135 patients (17.3%). For each of the ICD/CPT, PRBC, and Hgb definitions, the prevalence of major bleeding was 2.8% (n = 31), 7.4% (n = 81), and 5.4% (n = 59), respectively. Only 3.7% of bleeds (5/135) were captured by all three definitions and 19.3% (26/135) exclusively by any two pairwise definitions. The addition of PRBC transfusion and Hgb decline to ICD/CPT code definitions increased bleeding prevalence threefold. Among hospitalized adults undergoing TPE in the REDS-III study, the prevalence of major bleeding was 17.3%. The addition of PRBC and Hgb decline to ICD codes increased bleeding prevalence threefold. Future studies are needed to develop validated models that identify patients at risk for major bleeding during TPE.

The Management of Postoperative Atrial Fibrillation (POAF): A Systematic Review.

Postoperative atrial fibrillation (POAF) refers to new-onset atrial fibrillation (AF) that develops after surgery and is associated with an increased risk of mortality and thromboembolic events. The optimal management and treatment methods for POAF complications are not yet fully established. This systematic reviewaimed to evaluate the various treatment and management approachescurrently available in terms of their suitability, efficacy, and side effects in handling POAF incidence post-surgery. Google Scholar and PubMed electronic databases were searched extensively for relevant articlesexamining the various management techniques currently used to manage POAF and published between 2018 and 2023. Data were collected on the type of surgery the patients underwent, POAF definition period, intervention, and outcome of interest. Following a systematic assessment guided by the inclusion criteria, 10 of the 579 studies retrieved were included in this study, and 293,417 POAF cases were recorded. Three of these studies used different rhythm control and rate control treatments to manage POAF cases, while seven studies used various anticoagulation therapies to manage POAF incidence. For asymptomatic patients within one to three days of surgery, rate control is sufficient to manage POAF, and routine rhythm control is not needed; rhythm control should be reserved for patients who develop complications such as hemodynamic instability. Anticoagulation was performed in patients whose POAF exceededfour days after surgery. Anticoagulation was associated with an increased risk of mortality, stroke, thromboembolic events, and major bleeding in patients who underwent coronary artery bypass graft (CABG) surgery. In contrast, in a few other studies, anticoagulation treatment led to improved outcomes in patients who developed POAF. A wide range of management methods are available for POAF after different types of surgery. However, there is only limited evidence to guide the clinical practice. The data available are mainly retrospective and insufficient to accurately evaluate the efficacy of the various management methods available for POAF. Future research should make efforts to standardize the treatment for this condition.

Acute venous thromboembolism in patients with brain cancer: clinical course

BackgroundPatients with brain cancer have been excluded or were underrepresented in studies on the treatment of venous thromboembolism (VTE), mainly due to the fear of intracranial hemorrhage (ICH). ObjectivesThe aim of this study was to provide data on the risk of ICH, recurrent VTE, and major bleeding in patients with active brain cancer. MethodsThis was a multicenter, international cohort study at participating sites of the Registro Informatizado Enfermedad Tromboembólica Registry. Patients included in this study were classified as having known active brain cancer, active nonbrain cancer, or without active cancer. ICH at 3 months was the primary study outcome. ResultsOverall, 98,377 patients with VTE were included: 616 with active brain cancer, 16,807 with active nonbrain cancer, and 80,954 without active cancer. At 3 months follow-up, ICH occurred in 2.8%, 0.3%, and 0.2% of the patients, respectively, and was fatal in 1.3%, 0.2%, and 0.1%, respectively. Both rates of major bleeding (3.7% vs 3.2% vs 1.5%, respectively) and recurrent VTE (3.9% vs 3.4% vs 1.1%, respectively) were higher in patients with brain or nonbrain cancer than in patients without cancer. Glioblastomas were associated with a numerically higher risk of ICH, fatal ICH, and recurrent VTE than other brain tumors. ConclusionIn patients with VTE, active brain cancer was associated with a higher risk of ICH or fatal ICH than nonbrain or no active cancer. Further studies are needed to assess the value of different treatment approaches in patients with brain cancer and VTE.

The clinical outcomes of different doses of rivaroxaban in patients with isolated distal deep vein thrombosis

ObjectiveIsolated distal deep vein thrombosis (IDDVT) is defined as thrombosis involving the infrapopliteal veins. The optimal anticoagulant therapy of IDDVT remains controversial. This study aimed to assess whether reduced dose of rivaroxaban was suitable in patients with IDDVT. MethodsConsecutive patients with acute IDDVT were identified by reviewing the venous thromboembolism (VTE) registry databases. Outcomes including VTE recurrence, major bleeding, clinically relevant non-major (CRNM) bleeding, and death. Patients were followed until the first occurrence of any outcomes or the study end date (December 31, 2018). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed. ResultsA total of 1246 patients were divided into low-dose (10 or 15 mg/day; n = 716) and standard-dose (20 mg/day; n = 530) groups. The incidences of VTE recurrence, major bleeding, CRNM bleeding, and death between the two groups were 9.64% vs 5.66%, 1.68% vs 3.02%, 4.61% vs 8.68%, and 13.83% vs 10.75%, respectively. After the inverse probability of treatment weighting, HRs for standard-dose vs low-dose of VTE recurrence, major bleeding, CRNM bleeding, and death were 0.54 (95% CI, 0.35-0.84), 1.71 (95% CI, 0.80-3.67), 2.28 (95% CI, 1.40-3.74), and 1.30 (95% CI, 0.91-1.86), respectively. For the subgroup analysis, the interaction with anticoagulation duration and treatment was evident for VTE recurrence (P for interaction = .002), but not for major bleeding. Patients with residual vein thrombosis were associated with an increased risk of VTE recurrence (HR, 1.95; 95% CI, 1.29-2.95). The interaction between risk factors and residual vein thrombosis was evident for VTE recurrence (P for interaction = .085). ConclusionsStandard-dose rivaroxaban reduced the risk of VTE recurrence without increasing the risk of major bleeding in patients with IDDVT. Anticoagulant therapy for >1.5 months should be preferred over shorter durations. Residual vein thrombosis should be assessed as a predictor of recurrence in patients with IDDVT, especially for patients with non-transient factors.

Evaluating efficacy and safety of oral anticoagulation in adult patients with atrial fibrillation and cancer: A systemic review and meta-analysis

BackgroundAtrial fibrillation (AF) is common among patients with cancer. Patients with cancer and AF require anticoagulant therapy [direct oral anticoagulants (DOAC) or vitamin K antagonist (VKA)] for stroke and systemic embolism (SE) prevention. We sought to assess the rates of stroke/SE and major bleeding in patients with cancer and AF on oral anticoagulant therapy (DOAC or VKA). MethodsA systematic search of MEDLINE and EMBASE was conducted. The primary efficacy and safety outcome were stroke/SE and major bleeding (as per the International Society on Thrombosis and Haemostasis definition), respectively. Incidence rates (IR) were pooled using random effects model (event per 100 patient-years). Incidence rate ratios (IRR) were computed using a Poisson regression model with associated 95% confidence intervals (CI) using R software (version 4.0.3). ResultsOf the total 2,153 article records that were screened, 22 observational studies from 12 different countries were included in the meta-analysis (n = 94,980 patients). The IR of stroke/SE was 1.81 (95% CI: 0.89 to 3.68) and 3.41 (95% CI: 1.38 to 8.41) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.63 (95%CI: 0.47–0.84)). The IR of major bleeding was 2.59 (95%CI: 1.54 to 4.38) and 3.60 (95% CI: 1.68 to 7.71) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.76 (95% CI: 0.55 to 1.04)). ConclusionDOACs compared to VKA seem to provide a significant reduction in the risk of stroke/SE and a good risk-benefit ratio profile for safety outcomes in this patient population.

Optimising prediction of mortality, stroke, and major bleeding for patients with atrial fibrillation: validation of the GARFIELD-AF tool in UK primary care electronic records.

The GARFIELD-AF tool is a novel risk tool that simultaneously assesses the risk of all-cause mortality, stroke or systemic embolism, and major bleeding in patients with atrial fibrillation (AF). To validate the GARFIELD-AF tool using UK primary care electronic records. A retrospective cohort study using the Clinical Practice Research Datalink (CPRD) linked with Hospital Episode Statistics data and Office for National Statistics mortality data. Discrimination was evaluated using the area under the curve (AUC) and calibration was evaluated using calibration-in-the-large regression and calibration plots. A total of 486 818 patients aged ≥18 years with incident diagnosis of non-valvular AF between 2 January 1998 and 31 July 2020 were included; 50.6% (n = 246 425/486 818) received anticoagulation at diagnosis The GARFIELD- AF models outperformed the CHA2DS2VASc and HAS-BLED scores in discrimination ability of death, stroke, and major bleeding at all the time points. The AUC for events at 1 year for the 2017 models were: death 0.747 (95% confidence interval [CI] = 0.744 to 0.751) versus 0.635 (95% CI = 0.631 to 0.639) for CHA2DS2VASc; stroke 0.666 (95% CI = 0.663 to 0.669) versus 0.625 (95% CI = 0.622 to 0.628) for CHA2DS2VASc; and major bleeding 0.602 (95% CI = 0.598 to 0.606) versus 0.558 (95% CI = 0.554 to 0.562) for HAS- BLED. Calibration between predicted and Kaplan- Meier observed events was inadequate with the GARFIELD-AF models. The GARFIELD-AF models were superior to the CHA2DS2VASc score for discriminating stroke and death and superior to the HAS-BLED score for discriminating major bleeding. The models consistently underpredicted the level of risk, suggesting that a recalibration is needed to optimise its use in the UK population.

Impact of anemia on major bleeding in patients taking oral anticoagulants for nonvalvular atrial fibrillation.

Anemia is encountered in patients with nonvalvular atrial fibrillation (NVAF) on oral anticoagulants (OACs) but the prognostic impact was not well scrutinized in real-world settings. We conducted a historical multicenter registry of patients with NVAF taking OACs at 71 centers in Japan. Those with mechanical heart valves or a history of pulmonary thrombosis or deep venous thrombosis were excluded. Anemic patients were divided into three groups of hemoglobin (Hb) level: moderate/severe (Hb < 11.0 g/dL), mild (men: Hb of 11.0-12.9 g/dL; women: Hb of 11.0-11.9 g/dL), and no anemia. The endpoints included major bleeding, hemorrhagic stroke, ischemic events, ischemic stroke, and all-cause mortality. Among 7558 consecutive patients (mean age, 73 years; men 67%) registered in February 2013 and followed until February 2017, 2100 (28%) patients had anemia. The anemic patients were older (moderate/severe: 79 years; mild: 77 years; no anemia: 71 years, p < .001), and HAS-BLED score was significantly higher in the anemic patients (p < .001). The cumulative incidences at 4 years of major bleeding in moderate/severe, mild, and no anemia group, were 14.9%, 10.7%, and 6.4%, respectively. The adjusted hazard ratios (HRs) (95% confidential intervals (CIs)) of major bleeding of moderate/severe and mild anemia group were 1.96 (1.49-2.58) and 1.48 (1.17-1.87) compared to no anemia group. The adjusted HRs (95% CIs) for ischemic events were 0.63 (0.39-0.99) and 1.03 (0.76-1.39). The severity of anemia in the patients with NVAF on OACs was associated with major bleeding.

Incidence of major bleeding in patients with chronic lymphocytic leukemia receiving ibrutinib and therapeutic anticoagulation

Increased rates of clinically significant bleeding have been reported with ibrutinib, however, limited data is available on the risk when given with concomitant therapeutic anticoagulation. We analyzed the incidence of major bleeding in 64 patient exposures that received ibrutinib with concomitant therapeutic anticoagulation. Major bleeding was observed in 5/64 (8%) patient exposures. The highest incidence was observed with rivaroxaban (3/17, 18%), followed by apixaban (2/35, 6%). No major bleeding events were seen with enoxaparin (n = 10). A total of 38% of patient exposures received a concomitant antiplatelet agent along with therapeutic anticoagulation. Among these patients, one (4%) experienced a fatal hemorrhage while taking ibrutinib, apixaban, and clopidogrel concomitantly. Our retrospective study observed a higher rate of major hemorrhage with combined DOAC with ibrutinib than historically reported with ibrutinib alone. This combination may be associated with increased risk of major bleeding and further prospective studies evaluating this risk are necessary.

Effect of frailty on major bleeding in octogenarian patients undergoing percutaneous coronary intervention.

There has been an increase in the number of percutaneous coronary intervention (PCI) procedures performed in octogenarian patients due to increased life expectancy and developments in modern medicine. Frailty is associated with the aging process, gradual loss of multiple body functions, and poor health outcomes. We examined the association between frailty and major bleeding in octogenarian patients undergoing PCI. We retrospectively analyzed the records of two local research hospitals in Turkey. In total, 244 patients were enrolled in this study. Patients were divided into two groups based on their Clinical Frailty Scale (CFS) score. The non-frail group included patients with CFS scores of 1 (very fit) to 4 (living with very mild frailty), while the frail group included those with CFS scores of 5 (living with mild frailty) to 9 (terminally ill). Of the 244 patients, 131 were classified into the non-frail group and 113 into the frail group. Ticagrelor use was significantly more common in the non-frail group (31.3% vs. 20.4%, p=0.036). Major bleeding was more common in the frail than non-frail group (20.4% vs. 6.1%, p<0.001). The rates of stroke and all-cause death were higher in the frail than in non-frail group (stroke 15.9% vs. 3.8%, p<0.001, as well as all-cause mortality rate (27.4% vs. 2.3%, p<0.001). Frailty is an independent predictor of major bleeding in patients undergoing PCI for acute coronary syndrome. Use of the P2Y12 inhibitor ticagrelor increases the risk of major bleeding in frail patients.

Comparison between ticagrelor and clopidogrel in myocardial infarction patients with high bleeding risk- A report from the SWEDEHEART registry.

Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR. This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. HBR was defined as a PRECISE-DAPT score ≥ 25. Information on ischemic events, major bleeding and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25,042 HBR patients, of whom 11,848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69,040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect. We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients.

Significant Impact of Age on Mortality and Non-significant Impact of Age on Thrombosis and Major Bleeding in Patients with COVID-19: From the CLOT-COVID Study.

There is scarce data on the impact of age on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into five groups according to age strata; -19, 20-39, 40-59, 60-79, and 80- years. Most patients under 19 had mild COVID-19 on admission (99%), while older patients had more severe COVID-19. The incidence rates of clinical outcomes during hospitalization in patients aged ≤ 19, 20-39, 40-59, 60-79, and 80 ≥ years were 0.0%, 0.5%, 2.2%, 2.7%, and 1.5% for thrombosis; 0.0%, 1.2%, 1.5%, 3.4%, and 2.0% for major bleeding; and 0.0%, 0.4%, 2.0%, 12.1%, and 16.8% for all-cause death, respectively. In the stratified analysis according to COVID-19 severity on admission, the incidences of thrombosis were generally higher among patients with more severe status, although those were not significantly different among age strata in all sub-types of COVID-19 severity. However, the incidences of all-cause death were significantly higher with increasing age in all sub-types of COVID-19 severity. In the current large observational study of patients with COVID-19, the risk of mortality became markedly higher with increased age. However, the risks of thrombosis and major bleeding did not necessarily increase as age increases, which seemed to be consistent irrespective of COVID-19 severity on admission.

The prognostic value of ORBIT risk score in predicting major bleeding in patients with acute coronary syndrome

BackgroundThe most significant adverse effect of antithrombotic medication in acute coronary syndrome (ACS) is major bleeding, which is related to increased mortality. Studies on ORBIT risk score in predicting major bleeding in ACS patients are limited. ObjectiveThis research aimed to examine whether the ORBIT score calculated at the bedside can identify major bleeding risk in patients with ACS. MethodsThis research was retrospective, observational, and conducted at a single center. Analyses of receiver operating characteristics (ROC) were utilized to define the diagnostic value of CRUSADE and ORBIT scores. The predictive performances of the two scores were compared using DeLong's method. Discrimination and reclassification performances were evaluated by the integrated discrimination improvement (IDI), and net reclassification improvement (NRI). ResultsThe study included 771 patients with ACS. The mean age was 68.7 ± 8.6 years, with 35.3 % females. 31 patients had major bleeding. Twenty-three of these patients were BARC 3 A, five were BARC 3 B, and three were BARC 3 C. Bleeding history [OR (95 % CI), 2.46 (1.02–5.94), p = 0.021], hemoglobin levels [OR (95 % CI), 0.54 (0.45–0.63), p < 0.001], and age > 74 years [OR (95 % CI), 1.03 (1.01–1.06), p = 0.039] were independent predictors of major bleeding. The ORBIT score was an independent predictor of major bleeding in the multivariate analysis: continuous variables [OR (95 % CI), 2.53 (2.61–3.95), p < 0.001] and risk categories [OR (95 % CI), 3.06 (1.69–5.52), p < 0.001]. Comparison of c-indexes for major bleeding events revealed a non-significant difference for the discriminative ability of the two tested scores (p = 0.07) with a continuous NRI of 6.6 % (p = 0.026) and an IDI of 4.2 % (p < 0.001). ConclusionIn ACS patients, the ORBIT score independently predicted major bleeding.

Stroke Risk with Warfarin vs. NOACs in Artificial Heart Valves: a Meta-Analysis (S45.004)

<h3>Objective:</h3> This systematic review and meta-analysis evaluates multiple clinical outcomes between warfarin and NOACs in patients with artificial heart valves. <h3>Background:</h3> Although novel oral anticoagulants (NOAC) have been proven as effective alternatives to warfarin in patients with atrial fibrillation, the effectiveness of NOACs in patients with artificial (bioprosthetic and mechanical) heart valves is not known. <h3>Design/Methods:</h3> PubMed, CINHAL, and Clinicaltrials.gov were searched through May 2022 for studies comparing clinical outcomes of adults with artificial heart valves that received warfarin vs. NOACs. Data was pooled with Der Simonian and Laird’s random effects model. <h3>Results:</h3> Eight studies (n = 183167, 38% female) met the criteria for study inclusion. Four were randomized control trials (RCTs) and four were retrospective cohort studies. Mechanical and bioprosthetic valves were represented in 14.7% and 85.3% of patients respectively. There was no statistically significant difference between NOACs and warfarin for all bleeding, all-cause mortality, TIA, systemic embolism, and all-stroke outcomes. Overall Warfarin led to 22% more major bleeding (OR = 1.22, 95% CI = [1.05, 1.41], p = 0.01) and more ischemic stroke (OR = 1.72, 95% CI = [1.1, 2.68], p = 0.02) compared to NOACs. Also amongst patients with bioprosthetic heart valves, Warfarin led to 33% more major bleeding compared to NOACs (OR = 1.33, 95% CI = [1.06, 1.66]). However, NOACs led to 65% more major bleeding compared to warfarin among those with mechanical heart valves (OR = 0.35, 95% CI = [0.18, 0.67]). <h3>Conclusions:</h3> Compared with warfarin, NOACs reduced the risk of ischemic stroke and major bleeding in patients with artificial heart valves. NOACs reduced the risk of ischemic stroke and major bleeding in patients with bioprosthetic heart valves, but not in patients with mechanical heart valves compared to Warfarin. <b>Disclosure:</b> Mr. Srivastava has nothing to disclose. Ms. Almader-Douglas has nothing to disclose. Dr. Deo has nothing to disclose. Dr. Sharma has nothing to disclose.

Incidence, source, and prognostic impact of major bleeding across the spectrum of aortic stenosis

Severe aortic stenosis (AS) has been associated with bleeding. However, there is a lack of prospective assessment of bleeding events and their clinical significance in a large population of outpatients with variable degree of AS severity. To assess the incidence, source, determinants, and prognostic impact of major bleeding in patients with variable degree of AS severity. Between May 2016 and December 2017, consecutive outpatients were included. Major bleeding was defined as type ≥3 bleed using the Bleeding Academic Research Consortium definition. Cumulative incidence was calculated with death as the competing event. Data was censored at time of aortic valve replacement. Among 2,830 patients, 46 major bleeding events occurred (0.7%/year) during a median follow-up of 2.1 years (interquartile range: 1.4-2.7). Most frequent sites of bleeding were gastrointestinal (50%) and intracranial (30.4%). Major bleeding was significantly associated with all-cause mortality (hazard ratio: 5.93 (95% confidence interval 3.64-9.65); P < .001). AS severity was associated with major bleedings (P=.041). By multivariable analysis, severe AS was an independent determinant of major bleeding (hazard ratio vs mild AS: 3.59 [95% confidence interval 1.56-8.29]; P=.003). The increased risk of bleeding associated with severe AS was significantly exacerbated in patients using oral anticoagulation. In AS patients, major bleeding is rare but a strong independent predictor of death. AS severity is a determinant of bleeding events. Severe AS and oral anticoagulation should be identified as an association at very high risk of major bleeding.

Sex Differences Among Patients Receiving Edoxaban vs Vitamin K Antagonist for Atrial Fibrillation After TAVR

BackgroundIn the ENVISAGE-TAVI AF (Edoxaban vs Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation–Atrial Fibrillation) trial, edoxaban was noninferior to vitamin K antagonists (VKA) for a composite outcome of ischemic and bleeding complications but increased major bleeding in patients with atrial fibrillation after successful transcatheter aortic valve replacement. Women are at higher risk of bleeding and stroke than men after transcatheter aortic valve replacement. It is unclear whether the effect of edoxaban on these complications varies in relation to sex. ObjectivesThis study was to assess the effect of edoxaban vs VKA according to sex in the ENVISAGE-TAVI AF trial. MethodsThe primary outcomes were net adverse cardiovascular events (NACE) and major bleeding, assessed considering the effective time on study medication (safety analysis). ResultsOut of 1,377 patients, 658 (47.8%) were women. Risks for ischemic and major bleeding outcomes were similar between women and men. Edoxaban compared to VKA was associated with a similar risk of NACE in women (HR: 1.16; 95% CI: 0.81-1.65) and men (HR: 1.08; 95% CI: 0.76-1.53; P for interaction = 0.820) and a higher risk of major bleeding in both sexes (P for interaction = 0.170). The risk increase of major bleeding was attenuated in women (HR: 1.11; 95% CI: 0.69-1.79) as compared to men (HR: 1.75; 95% CI: 1.07-2.85). There were no treatment-related differences for ischemic complications in both sexes. ConclusionsEdoxaban compared to VKA was associated with a similar risk of NACE and higher risk of major bleeding in both sexes. The increase in bleeding complications with edoxaban was attenuated in women.

Thromboembolism and Major Bleeding in Patients with Atrial Fibrillation and EHRA Type 2 Valvular Heart Disease: The Jordan Atrial Fibrillation (JoFib) Study.

The risks of thromboembolism and major bleeding in atrial fibrillation (AF) patients were assessed according to the "Evaluated Heartvalves, Rheumatic or Artificial" (EHRA) classification. Additionally, the safety and efficacy of vitamin K antagonists (VKAs) and non-VKA oral anticoagulants (NOACs) were compared in AF patients with EHRA type 2 valvular heart disease (VHD) versus those with no VHD. AF patients enrolled in the "Jordan Atrial Fibrillation (JoFib)" study were followed up for thromboembolic events and major bleeding at 30, 180, and 365 days. Patients in the EHRA type 2 VHD and non-VHD groups were sub-grouped to compare different OACs. 2020 AF patients were recruited. The thromboembolic risk was higher in EHRA type 2 VHD patients compared to non-VHD controls. Major bleeding also occurred at higher rates in EHRA type 2 patients. In addition, NOACs were more effective in preventing thromboembolic events than VKAs and non-anticoagulation in EHRA type 2 VHD patients. Furthermore, EHRA type 2 VHD patients taking rivaroxaban had significantly less thromboembolic risk than their non-anticoagulated counterparts. At the same time, apixaban and warfarin did not significantly lower the risk of thromboembolism compared to non-anticoagulation. AF patients with EHRA type 2 VHD are at significant risk of thromboembolism and major bleeding. Furthermore, NOACs were more effective than VKAs in preventing thromboembolic events in this group of patients without conferring an added risk of major bleeding. Moreover, rivaroxaban appears to be particularly efficacious.

Relation between laxative use and risk of major bleeding in patients with atrial fibrillation and heart failure

Constipation has been reported to increase the risk of cardiovascular mortality. Patients with atrial fibrillation (AF) and heart failure (HF) have more comorbidities and an increased bleeding risk. However, it remains unclear whether constipation is associated with an increased risk of incident bleeding complications in AF with HF. Here, we investigated the association between constipation requiring laxatives and major bleeding in AF and HF. We retrospectively analyzed the medical records of 370 consecutive patients hospitalized for AF and congestive HF. Constipation was defined as regularly taking laxatives or having at least two prescriptions for a ≥ 30-day supply of laxatives. Sixty patients experienced major bleeding events during a median follow-up of 318 days. The most common sites of bleeding were lower gastrointestinal (28%, 17/60), upper gastrointestinal (27%, 16/60), and intracranial (20%, 12/60). There were 33 (55%) patients with constipation in the bleeding group and 107 (35%) in the non-bleeding group (P = 0.004). Multivariate Cox regression analysis adjusted for HAS-BLED score, hemoglobin, and direct oral anticoagulant use showed that constipation (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.11–3.08; p = 0.019) was a significant risk factor for major bleeding. We found a significant association between constipation requiring laxatives and major bleeding in patients with AF and HF. These findings indicate the need for constipation prevention in these patients to avoid reliance on invasive defecation management, including laxatives.

New score for predicting major bleeding in patients with atrial fibrillation using direct oral anticoagulants

PurposeOur aim was to identify factors associated with major bleeding in patients with atrial fibrillation (AF) on direct oral anticoagulants (DOACs) and to construct and externally validate a predictive model that would provide a validated tool for clinical assessment of major bleeding. MethodsIn the development cohort, prediction model was built by logistic regression, the area under the curve (AUC), and Nomogram. External validation, analytical identification and calibration of the model using AUC, calibration curves and Hosmer-Lemeshow test. ResultsThe development cohort consisted of 4209 patients from 7 centers and the external validation cohort consisted of 1800 patients from 12 centers. Multifactorial analysis showed that age > 65 years, history of bleeding, anemia, vascular disease, antiplatelet therapy/non-steroidal anti-inflammatory drugs and rivaroxaban were independent risk factors for major bleeding, and gastrointestinal protective agents was a protective factor. The Alfalfa-MB model was constructed using these seven factors (AUC = 0.807), and in the external validation cohort, the model showed good discriminatory power (AUC = 0.743) and good calibration (Hosmer-Lemeshow test P value of 0.205). The predictive power of the six bleeding scores was ORBIT (AUC = 0.706), HAS-BLED (AUC = 0.648), ATRIA (AUC = 0.645), HEMORR2 HAGES (AUC = 0.632), ABC (AUC = 0.619) and Shireman (AUC = 0.599) in descending order. ConclusionBased on 7 factors, we derived and externally validated a predictive model for major bleeding with DOACs in patients with AF (Alfalfa-MB). The model has good predictive value and may be an effective tool to help reduce the occurrence of major bleeding in patients with DOACs.

Risk factors for recurrence and major bleeding in patients with cancer-associated venous thromboembolism

Risks of recurrence and treatment-emergent bleeding are high in patients with cancer-associated venous thromboembolism (VTE) but factors associated with these risks remain substantially undefined.The aim of this analysis in patients with cancer-associated VTE included in the Caravaggio study was to identify risk factors for recurrent VTE and major bleeding. Variables potentially predictive for recurrent VTE or major bleeding were evaluated in a Cox proportional hazard multivariable analysis with backward variable selection.Recurrent VTE occurred in 78 patients (6.8%) and major bleeding in 45 (3.9%). Independent risk factors for recurrent VTE were deep vein thrombosis (DVT) as index event (Hazard ratio (HR) 1.84, 95% CI 1.17–2.88), ECOG status of 1 or more (HR 1.95, 95% CI 1.11–3.43), pancreatic or hepatobiliary cancer site (HR 2.20, 95% CI 1.19–4.06), concomitant anti-cancer treatment (HR 1.98, 95% CI 1.03–3.81) and creatinine clearance (HR 1.10, 95% CI 1.00–1.20 for every 10 ml/min absolute increase). Independent risk factors for major bleeding were ECOG status of 2 (HR 2.31, 95% CI 1.24–4.29), genitourinary cancer site (HR 2.72, 95% CI 1.28–5.77), upper gastrointestinal cancer site (HR 3.17, 95% CI 1.22–8.23), and non-resected luminal gastrointestinal cancer (HR 2.77, 95% CI 1.38–5.56).This analysis of the Caravaggio study in patients with cancer-associated VTE who were on standardized anticoagulant treatment identified five independent predictors for recurrent VTE and four independent predictors of treatment-emergent major bleeding. Considering these risks could help clinicians to optimize the anticoagulant treatment in patients with cancer-associated VTE.