Risk Of Major Bleeding In Patients Research Articles

Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Liver Cirrhosis.

Comparing direct oral anticoagulants (DOACs) and warfarin's efficacy and safety in patients with nonvalvular atrial fibrillation (AF) and liver cirrhosis (LC). Evidence of the pharmacodynamics of DOACs is limited in patients with AF and LC. A retrospective cohort study was conducted in the largest hospital system in Taiwan, involving patients with AF and LC for the years 2012 to 2021. Hazards of thromboembolic events (ischemic stroke, transient ischemic attack, and systemic embolism), intracranial hemorrhage, gastrointestinal, major bleeding, and all-cause mortality were investigated with a new-user, active comparator design. Inverse probability of treatment weighting was applied to balance potential confounders between treatment groups. In total, 478 DOAC users and 247 warfarin users were included. DOACs and warfarin demonstrated similar trends in preventing thromboembolic events, namely ischemic stroke [adjusted hazard ratio (aHR), 1.05 (95% CI: 0.42-2.61)], transient ischemic attack [aHR, 1.36 (95% CI: 0.18-10.31)], and systemic embolism [aHR, 0.49 (95% CI: 0.14-1.70)]. DOAC use was associated with a similar risk of intracranial hemorrhage [aHR, 0.65 (95% CI: 0.26-1.59)] and gastrointestinal bleeding [aHR, 0.64 (95% CI: 0.39-1.03)], a decreased risk of major bleeding [aHR, 0.64 (95% CI: 0.42-0.99)], and a reduction in mortality [aHR, 0.73 (95% CI: 0.54-0.99)]. DOAC users exhibited a significant reduction in major bleeding risk in patients with Child-Pugh class A (aHR, 0.48; 95% CI: 0.33-0.70). DOACs showed potential safety advantages over warfarin for patients with nonvalvular AF and LC, particularly in reducing major bleeding risk in those with Child-Pugh class A.

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.

Long-term stroke and major bleeding risk in patients with non-valvular atrial fibrillation: A comparative analysis between non-vitamin K antagonist oral anticoagulants and warfarin using a clinical data warehouse.

Non-vitamin K antagonist oral anticoagulants (NOACs) has been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation (AF) since 2014. Many studies based on claim data revealed that NOACs had comparable effect to warfarin in preventing ischemic stroke with fewer hemorrhagic side effects. We analyzed the difference in clinical outcomes according to the drugs in patients with AF based on the clinical data warehouse (CDW). We extracted data of patients with AF from our hospital's CDW and obtained clinical information including test results. All claim data of the patients were extracted from National Health Insurance Service, and dataset was constructed by combining it with CDW data. Separately, another dataset was constructed with patients who could obtain sufficient clinical information from the CDW. The patients were divided NOAC and warfarin groups. The occurrence of ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, and death were confirmed as clinical outcome. The factors influencing the risk of clinical outcomes were analyzed. The patients who were diagnosed AF between 2009 and 2020 were included in the dataset construction. In the combined dataset, 858 patients were treated with warfarin, 2,343 patients were treated with NOACs. After the diagnosis of AF, the incidence of ischemic stroke during follow-up was 199 (23.2%) in the warfarin group, 209 (8.9%) in the NOAC group. Intracranial hemorrhage occurred in 70 patients (8.2%) among the warfarin group, 61 (2.6%) of the NOAC group. Gastrointestinal bleeding occurred in 69 patients (8.0%) in the warfarin group, 78 patients (3.3%) in the NOAC group. NOAC's hazard ratio (HR) of ischemic stroke was 0.479 (95% CI 0.39-0.589, p < 0.0001), HR of intracranial hemorrhage was 0.453 (95% CI 0.31-0.664, p < 0.0001), and HR of gastrointestinal bleeding was 0.579 (95% CI 0.406-0.824, p = 0.0024). In the dataset constructed using only CDW, the NOAC group also had a lower risk of ischemic stroke and intracranial hemorrhage than warfarin group. In this CDW based study, NOACs are more effective and safer than warfarin in patients with AF even with long-term follow-up. NOACs should be used to prevent ischemic stroke in patients with AF.

Postoperative major bleeding risk in patients using oral antiplatelets and/or anticoagulants after laparoscopic gastric cancer surgery.

The use of antiplatelet and/or anticoagulant therapies has become common. In rare cases, these therapies may increase the risk of dangerous postoperative bleeding. We investigated the association of antiplatelets and/or anticoagulants with postoperative major bleeding risk in laparoscopic gastric cancer surgery. We retrospectively enrolled 3,663 gastric cancer patients (antiplatelet/anticoagulant group, 518; control group, 3,145) who had undergone laparoscopic surgery between January 2012 and December 2017. To minimize selection bias, 508 patients in each group were matched using propensity score matching (PSM) method. The primary outcome was postoperative major bleeding. Secondary outcomes were intraoperative, postoperative transfusion and early complications. After PSM, postoperative major bleeding occurred in 10 (2.0%) and 3 cases (0.6%) in the antiplatelets/anticoagulants and control groups, respectively (P = 0.090). Intraoperative and postoperative transfusions were not significantly different between 2 groups (2.4% vs. 1.4%, P = 0.355 and 5.5% vs. 4.3%, P = 0.469). Early complications developed in 58 (11.4%) and 43 patients (8.5%) in the antiplatelets/anticoagulants and control groups, respectively (P = 0.142). The mean amounts of intraoperative and postoperative transfusions were not significantly different between the groups (366.67 ± 238.68 mL vs. 371.43 ± 138.01 mL, P = 0.962; 728.57 ± 642.25 mL vs. 508.09 ± 468.95 mL, P = 0.185). In multivariable analysis, male (P = 0.008) and advanced stage (III, IV) (P = 0.024) were independent significant risk factors for postoperative major bleeding. Preoperative antiplatelets and/or anticoagulants administration did not significantly increase the risk of postoperative major bleeding after laparoscopic gastric cancer surgery.

Efficacy and safety of direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism: A systematic review and Bayesian network meta-analysis

IntroductionDirect oral anticoagulants (DOACs) could effectively prevent the occurrence of cancer-associated venous thromboembolism (CAVTE), which incidence rate was estimated to be 4–20%. But the efficacy and safety remain controversial between DOACs and low molecular weight heparin (LMWH). Materials and methodsPubMed, Cochrane Library, Embase, ClinicalTrials.gov databases for randomized controlled trials (RCTs) were systematically searched from inception to March 15, 2022. A random-effects model was used to report the odds ratio (OR) and 95% confidence interval (CI) for both direct and network meta-analyses. ResultsSeven studies were included totaling 3242 patients. A lower rate of recurrence VTE was noted in the DOACs compared with LMWH (OR 0.62, 95% CI 0.47–0.82, I2=0.0%). The aspect of major bleeding (MB) was similar (OR 1.30, 95% CI 0.77–2.18, I2=34.9%). When assessing clinically relevant nonmajor bleeding (CRNMB) (OR 1.61, 95% CI 1.17–2.22, I2=20.7%) and clinically relevant bleeding (CRB) (OR 1.39, 95% CI 1.11–1.74, I2=0.0%), a higher risk of events was observed in DOACs. In subgroup analyses, the MB of gastrointestinal and genitourinary malignancies had a higher rate in the DOACs. For ranking, apixaban ranked the first in prevention of VTE and reducing MB events. Edoxaban had the highest risk drug in MB. In terms of CRNMB and CRB, LMWH showed the lowest risk. ConclusionsCompared with LMWH, DOACs seemed to have a decreased risk of recurrence VTE while increasing CRNMB and CRB. DOACs and LMWH were equivalent to the aspect of MB, but DOACs had a higher MB risk in patients with gastrointestinal and genitourinary malignancies. Apixaban may be the lowest risk compared to the other DOACs in precaution of VTE and reducing bleeding events.

Major Bleeding Risk in Patients With Non-valvular Atrial Fibrillation Concurrently Taking Direct Oral Anticoagulants and Antidepressants.

Direct oral anticoagulants (DOACs) are commonly prescribed with antidepressants that may increase bleeding risk. Here we assessed the association between DOACs with and without concurrent antidepressants and major bleeding risk in patients with atrial fibrillation (AF) by a retrospective cohort study included patients with AF who received prescriptions of DOACs in Taiwan’s National Health Insurance database between 2012 and 2017. Adjusted rate ratio (ARR) of major bleeding was calculated by comparing incidence rate adjusted with Poisson regression and inverse probability of treatment weighting using the propensity score between patient-times with and without antidepressants. Among 98863 patients with AF, concurrent use of bupropion with DOACs increased the risks of all major bleeding (ARR: 1.49, 95% CI: 1.02–2.16) and gastrointestinal hemorrhage (ARR: 1.57, 95% CI: 1.04–2.33). An increased risk of intracerebral hemorrhage (ICH) was associated with the combinations of DOACs with selective serotonin reuptake inhibitors (SSRIs, ARR: 1.38, 95% CI: 1.08–1.76), particularly in paroxetine (ARR: 2.11, 95% CI: 1.17–3.81), and tetracyclic antidepressants (TeCAs, ARR: 1.34, 95% CI: 1.01–1.78). In subgroup analyses stratified by individual NOACs, SSRIs increased the risk of ICH in the dabigatran-treated patients (ARR: 1.55, 95% CI: 1.04–2.33). The combinations of apixaban and serotonin-norepinephrine reuptake inhibitors (SNRIs) were associated with a higher risk of all major bleeding (ARR: 1.63, 95% CI: 1.04–2.55). These results clearly indicate the drug–drug interactions between DOACs and antidepressants, which should be carefully considered when prescribing DOACs in adult patients. Careful monitoring for bleeding should be performed while concurrently prescribing DOACs with bupropion, SSRI, SNRI, and TeCA. Concomitant use of DOACs and TCAs may be a relatively safe strategy for patients with AF.

230 Machine Learning Models for Predicting Ischemic Stroke and Major Bleeding Risk in Patients with Atrial Fibrillation

Background Risk scores such as CHA2DS2-VASc and HAS-BLED are used to assess stroke and bleeding risk respectively and choose appropriate antithrombotic therapy in patients with atrial fibrillation (AF). The application of ML models may improve risk prediction and identification of potential risk factors. Objective To investigate the usefulness of ML methods in estimating one-year risk of ischemic stroke and major bleeding in patients after hospitalisation with AF. Methods We identified adults with a history of non-valvular AF or atrial flutter who were admitted to a tertiary or secondary hospital in Perth, Western Australia from 2009 to 2016 using linked clinical and administrative data. Based on all the available risk factors in the data including individual risk factors in the scores, we built ML models and compared their predictive performance [Area under the receiver operating characteristic curve (AUC)] with the standard risk scores. Results There were 9,634 patients in the study cohort with a mean age of 77 years and 46% were female. 2407 patients died (n=1636) or were readmitted for ischemic stroke (n=157) and major bleeding (n=614) within one year after the first admission. All-cause death was treated as a competing risk. Gradient Boosting Machine identified nonconventional risk factors and achieved the best prediction (ischemic stroke: AUC 0.67 vs 0.64 for CHA2DS2-VASc; major bleeding: AUC 0.66 vs 0.53 for HAS-BLED). Conclusion ML models can identify nonconventional risk factors and also outperform commonly used risk scores for predicting ischemic stroke and major bleeding in patients with AF.

GARFIELD-AF model for prediction of stroke and major bleeding in atrial fibrillation: a Danish nationwide validation study

ObjectivesTo externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular...

GW29-e0757 Development and validation of a modified CRUSADE score for predicting in-hospital major bleeding risk in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention

Percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) reduce ischemic events but increase in-hospital bleeding. The prediction of bleeding risk can optimize the choice of antithrombotic therapy after PCI. However, existing models are not well suited

Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED.

To develop and externally validate a prediction model for major bleeding in patients with a TIA or ischemic stroke on antiplatelet agents. We combined individual patient data from 6 randomized clinical trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial were performed to study the association between predictors and major bleeding. A risk prediction model was derived and validated in the PERFORM trial. Performance was assessed with the c statistic and calibration plots. Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI] 4.4%-4.9%). Predictors were male sex, smoking, type of antiplatelet agents (aspirin-clopidogrel), outcome on modified Rankin Scale ≥3, prior stroke, high blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes (S2TOP-BLEED). The S2TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60-0.64) and showed good calibration in the development data. Major bleeding risk ranged from 2% in patients aged 45-54 years without additional risk factors to more than 10% in patients aged 75-84 years with multiple risk factors. In external validation, the model had a c statistic of 0.61 (95% CI 0.59-0.63) and slightly underestimated major bleeding risk. The S2TOP-BLEED score can be used to estimate 3-year major bleeding risk in patients with a TIA or ischemic stroke who use antiplatelet agents, based on readily available characteristics. The discriminatory performance may be improved by identifying stronger predictors of major bleeding.

Do Genetic Contributors to Warfarin Responsiveness or Common Thrombophilias Influence the Risk of Major Bleeding in Patients on Extended Duration Vitamin K Antagonist (VKA) for Venous Thromboembolic Disease?

Background: Recent studies have indicated that genetic factors such as polymorphisms in the CYP2C9 and the VKORC1 genes play an important role in vitamin K antagonist (VKA) response and perhaps bleeding. There are also data to suggest, especially for factor V Leiden, that thrombophilia may confer a decreased risk of bleeding (which could explain its persistence and high prevalence in the population). The influence of major genetic factors on risk of bleeding have not previously been evaluated in large prospective cohort studies of patients with VTE on extended (treatment after the first 3 to 6 months) VKA therapy.Aims: We sought to determine the effect of genetic variants that influence warfarin metabolism and thrombophilias on the rates of major bleeding during extended VKA therapy in patients with VTE disease.Methods: The Bleeding Risk study is a multicentre, multinational prospective cohort study of patients on extended VKA for unprovoked VTE, or provoked VTE with prior VTE. Patients were enrolled after at least 3 months of VKA. All major bleeding events during long term VKA were captured and adjudicated. A blood sample was taken from each patient at their first study visit and analysed in a central lab to identify the following genetic variant types: CYP2C9*2 (C/T), CYP2C9*3 (T/G), 1639G-A (G/A), Factor V Leiden (G/A: FVL), CYP4F2 (G/A), and Prothrombin gene 20210 variant (PGV). Rates of major bleeding were then evaluated for patients with each genetic variant in isolation and in combination.Results: 2290 of the 2514 patients enrolled at 12 sites have contributed over 7000 years of observation and were included in this analysis. The mean patient age was 60.2±14.7 years, 64% were male, 92% Caucasian, average BMI was 31.3, and 9% of patients were on antiplatelet agents. Patients were followed for a mean of 2.8 years (range, 0.1 to 6.8 years. 121 patients (4.8%) experienced at least one episode of major bleeding. The annual rate of bleeding was 1.7 per 100 patient-years of observation. The CYP2C9*2 variant heterozygous/homozygous versus wildtype (476 patients vs 1584) was protective against bleeding (Incidence risk ratio 0.5, p =0.01), CYP2C9*3 variant heterozygous/homozygous versus wildtype (215 patients vs 1845) was associated with major bleeding (Incidence risk ratio 2.0, p =0.01), VKORC1 and CYP4F2 had no association with major bleeding, and CYP2C9*3 variant heterozygous/homozygous in combination with wildtype CYP2C9*2 (186 patients) was associated with major bleeding (Incidence risk ratio 3.24, p =0.02). Both FVL (19% of patients) and PGV (8% of patients) had no effect on major bleeding, with p values > 0.35 for comparison of the wildtype to heterozygous/homozygous.Conclusion: This is the largest study we are aware of to determine if warfarin metabolic genotype variants and common thrombophilias influence major bleeding risk in patients followed long-term with extended duration VKA therapy for VTE. The thrombophilias do not influence bleeding risk but those with CYP2C9*3 hetero/homozygous inheritance had double the risk and CYP2C9*2 hetero/homozygous inheritance half the risk. There appears to be an interaction between the CYP2C9*2 and *3 genotypes. DisclosuresWells:BMS/Pfizer: Research Funding; Bayer Healthcare: Other: Speaker Fees and Advisory Board; Janssen Pharmaceuticals: Consultancy; Itreas: Other: Served on a Writing Committee. Kovacs:LEO Pharma: Honoraria; Bayer: Honoraria, Research Funding; Daiichi Sankyo Pharma: Research Funding; Pfizer: Honoraria, Research Funding. Anderson:Bayer Healthcare: Research Funding. Rodger:Canadian Agency for Drugs and Technologies in Health: Consultancy; Boehringer Ingelheim: Research Funding.

Combined Use of Bivalirudin and Radial Access in Acute Coronary Syndromes IsNot Superior to the Use of Either OneSeparately: Meta-Analysis of Randomized Controlled Trials.

The aim of this meta-analysis was to study the relation between access site and bivalirudin use on outcomes in patients with acute coronary syndrome (ACS). Bivalirudin and radial access use are 2 strategies that are increasingly used to lower major bleeding in patients with ACS undergoing invasive approaches. The interaction between these 2 strategies and the benefit of using them in combination are unclear. This analysis included randomized controlled trials that compared bivalirudin to heparin with or without glycoprotein IIb/IIIa inhibitors in patients with ACS and reported outcomes stratified by arterial access site. Meta-analyses of outcome data were performed on the basis of access site and anticoagulation regimen. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from event rates using random-effects models. Eight trials with a total of 27,491 patients were included. Bivalirudin reduced major bleeding risk in patients with femoral access (OR: 0.51; 95% CI: 0.46 to 0.6; p< 0.001) but not in patients with radial access (OR: 0.75; 95% CI: 0.45 to 1.26; p= 0.28). Moreover, radial access reduced major bleeding risk in patients treated with heparin (OR: 0.57; 95% CI: 0.43 to 0.77; p< 0.001) but not in patients treated with bivalirudin (OR: 0.96; 95% CI: 0.65 to 1.41; p= 0.83). There were no differences in major adverse cardiovascular events or all-cause mortality between bivalirudin and heparin, regardless of access site. Bivalirudin reduces bleeding risk only with femoral access, and radial access reduces bleeding risk only with heparin anticoagulation. Therefore, there is no additional benefit to the combined use of bivalirudin and radial access strategies in patients with ACS.

Major Bleeding and Hemorrhagic Stroke With Direct Oral Anticoagulants in Patients With Renal Failure: Systematic Review and Meta-Analysis of Randomized Trials

Direct oral anticoagulants (DOACs) are used as an alternative for traditional antithrombotic therapy. However, the safety profile of DOACs in patients with renal failure (RF) has not been determined. A systematic review was performed assessing the reported safety of DOACs compared with vitamin K antagonists (VKAs) in patients with RF and estimated creatinine clearance (eCrCL)< 50mL/min and eCrCL 50 to 80mL/min. MEDLINE, EMBASE, Cochrane, and the Clinical Trials Registry (ClinicalTrials.gov) were searched for randomized clinical trials up to November 2015. The data were pooled by using both traditional frequentist and Bayesian random effects models. Nine trials met the inclusion criteria. Among 94,897 participants, 54,667 (58%) had RF. Compared with VKAs, DOACs were associated with a significantly decreased risk formajor bleeding in patients with eCrCL 50 to 80mL/min (risk ratio, 0.87 [95%CI, 0.81-0.93]) and a nonsignificant decrease in the risk for major bleeding in patients with eCrCL< 50mL/min (risk ratio, 0.83 [95%CI, 0.68-1.02]); there was evidence of significant heterogeneity. Indirect comparisons, using Bayesian network analysis, indicated that apixaban was associated with a decreased rate of major bleeding compared with other DOACs inpatients with eCrCL <50mL/min. DOACs were associated with a significant decrease in the risk for hemorrhagic stroke compared with VKAs in patients with eCrCL< 50mL/min and 50 to 80mL/min. As a class, DOACs are associated with a reduced risk for hemorrhagic stroke compared with VKAs in patients with RF. However, DOACs may differ from each other in their relative risk for major bleeding in patients with eCrCL< 50mL/min. PROSPERO registry; No.: CRD42014013730; URL: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014013730.

Alcohol misuse, genetics, and major bleeding among warfarin therapy patients in a community setting.

Little is known about the impact of alcohol consumption on warfarin safety, or whether demographic, clinical, or genetic factors modify risk of adverse events. We conducted a case-control study to assess the association between screening positive for moderate/severe alcohol misuse and the risk of major bleeding in a community sample of patients using warfarin. The study sample consisted of 570 adult patients continuously enrolled in Group Heath for at least 2 years and receiving warfarin. The main outcome was major bleeding validated through medical record review. Cases experienced major bleeding, and controls did not experience major bleeding. Exposures were Alcohol Use Disorders Identification Test Consumption Questionnaire (AUDIT-C) scores and report of heavy episodic drinking (≥5 drinks on an occasion). The odds of major bleeding were estimated with multivariate logistic regression models. The overall sample was 55% male, 94% Caucasian, and had a mean age of 70 years. Among 265 cases and 305 controls, AUDIT-C scores indicative of moderate/severe alcohol misuse and heavy episodic drinking were associated with increased risk of major bleeding (OR = 2.10, 95% CI = 1.08-4.07; and OR = 2.36, 95% CI = 1.24-4.50, respectively). Stratified analyses demonstrated increased alcohol-related major bleeding risk in patients on warfarin for ≥1 year and in those with a low-dose genotype (CYP2C9*2/*3, VKORC1(1173G>A), CYP4F2*1), but not in other sub-groups evaluated. Alcohol screening questionnaires, potentially coupled with genetic testing, could have clinical utility in selecting patients for warfarin therapy, as well as refining dosing and monitoring practices.

(862) - CHA2DS2-Vasc and HAS-BLED Scores as Predictors of Ischemic and Hemorrhagic Stroke Risk After Left Ventricular Assist Device Implantation

CHA2DS2-VASc score predicts thromboembolic event risk and HAS-BLED score predicts major bleeding risk in patients on anticoagulation with atrial fibrillation. We aimed to evaluate if these scoring systems would be predictive of ischemic stroke and intracranial bleeding complications following continuous-flow left ventricular assist device (CF-LVAD) implantation.

Genetic Risk Factors for Major Bleeding in Patients Treated With Warfarin in a Community Setting

The influence of warfarin pharmacogenomics on major bleeding risk has been little studied in long-term users and non-specialist care settings. We conducted a case-control study to evaluate associations between CYP2C9*2/*3, VKORC1(1173), and CYP4F2*3 variants and major bleeding among patients treated with warfarin in a community setting. We calculated major bleeding odds ratios, adjusting for race, duration of warfarin use, age, gender, and body mass index. In 265 cases and 305 controls with 3.4 and 3.7 mean years of warfarin use, respectively, CYP4F2*3 was associated with decreased major bleeding risk (odds ratio: 0.62; 95% confidence interval: 0.43-0.91). CYP2C9*2/*3 and VKORC1(1173) had null associations overall, but there was a nonsignificant increase in major bleeding risk in patients with duration <6 months (odds ratio: 1.30; 95% confidence interval: 0.60-2.83; odds ratio: 1.23; 95% confidence interval: 0.57-2.64, respectively). In summary, in the largest study of warfarin pharmacogenomics and major bleeding to date, we found a 38% lower risk in patients with CYP4F2*3, potentially reflecting interaction with warfarin and dietary vitamin K intake and warranting additional evaluation.

Comparison of Medical Costs of Patients With Atrial Fibrillation Unsuitable for Warfarin Treatment With Apixaban or Aspirin Based on AVERROES Trial

The AVERROES trial name is the following: The Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial demonstrated that apixaban reduced the risk of stroke relative to aspirin, without significantly increasing major bleeding risk in patients with atrial fibrillation (AF) considered unsuitable for warfarin therapy. Based on AVERROES trial results, this study compared the medical costs for clinical end points among patients with AF treated with either apixaban or aspirin. Medical costs per patient-year for clinical events were determined. Based on clinical event rates for patients in the AVERROES trial, medical costs excluding drug costs were estimated for apixaban- and aspirin-treated patient groups. Based on AVERROES trial results, among patients with AF unsuitable for warfarin therapy, apixaban use was estimated to be associated with a mean medical cost avoidance of US$735 in a patient-year relative to aspirin. The primary driver was the significant reduction in ischemic stroke rate. The medical cost reduction associated with apixaban use was consistent in sensitivity analyses.

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Relation of the HAS-BLED Bleeding Risk Score to Major Bleeding, Cardiovascular Events, and Mortality in Anticoagulated Patients With Atrial Fibrillation

Stroke risk in atrial fibrillation (AF) using oral vitamin K antagonists is closely related to bleeding risk. The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR [international normalized ratio], elderly, drugs/alcohol concomitantly) bleeding score has demonstrated usefulness in assessing major bleeding risk in patients with AF. However, risk factors for warfarin-associated bleeding also predict stroke risk in patients with AF. We tested the usefulness of the HAS-BLED score for predicting both major bleeding and cardiovascular events in a cohort of anticoagulated patients with AF. We recruited 965 consecutive anticoagulated outpatients with permanent or paroxysmal AF who were stabilized for at least 6 months on oral anticoagulation (international normalized ratio, 2.0-3.0). Medical history and HAS-BLED score were assessed. Cox regression models were used to determine the association between clinical risk factors and bleeding episodes, adverse cardiovascular events, and mortality. The median HAS-BLED score was 2 (range, 0-6; 29% with a score ≥3 [ie, high risk]). Median follow-up was 861 days (range, 718-1016 days). Independent predictors for major bleeding were age ≥75 years (hazard ratio [HR], 1.74; 95% CI, 1.05-2.87; P=0.030), male sex (HR, 1.70; 95% CI, 1.03-2.80; P=0.036), renal impairment (HR, 2.12; 95% CI, 1.20-3.73; P=0.010), previous bleeding episode (HR, 6.00; 95% CI, 3.73-9.67; P<0.001), current alcohol consumption (HR, 2.28; 95% CI, 1.03-5.06; P=0.043), and concomitant malignant disease (HR, 2.17; 95% CI, 1.13-4.18; P=0.020). Independent predictors for adverse cardiovascular events were age >75 years (HR, 2.20; 95% CI, 1.40-3.46; P=0.001), heart failure (HR, 1.78; 95% CI, 1.20-2.86; P=0.001), and previous stroke (HR, 1.85; 95% CI, 1.20-2.86; P<0.001). The HAS-BLED score was highly predictive for major bleeding events (HR, 2.04; 95% CI, 1.68-2.49; P<0.001) and adverse cardiovascular events (HR, 1.51; 95% CI, 1.27-1.81; P<0.001). The incidence of both bleeding and adverse cardiovascular events was higher as HAS-BLED score increased, and crude bleeding rates only exceeded thrombotic events at a HAS-BLED score >3. The HAS-BLED score also predicted all-cause mortality (HR, 1.68; 95% CI, 1.40-2.01; P<0.001). The HAS-BLED score not only is useful in the assessment of bleeding risk, but also shows some predictive value for cardiovascular events and mortality in anticoagulated patients with AF, consistent with the relationship between thrombosis and bleeding. Nonetheless, the HAS-BLED score has been designed for predicting bleeding risk rather than thrombotic events per se, and specific risk scores for cardiovascular events and mortality should be applied for these events.

Increased major bleeding risk in patients with kidney dysfunction receiving enoxaparin: a meta-analysis

The elimination half-life and consequently the accumulation of enoxaparin increase as glomerular filtration rate (GFR) decreases. A dose adjustment for patients with a GFR <30 ml/min is recommended and considered relatively safe. Our intention was to identify whether the use of enoxaparin is safe and to determine what impact an enoxaparin dose adjustment has on patients with a GFR <60 ml/min. A PubMed search and meta-analysis of literature were performed. Studies were analyzed to compare enoxaparin versus other heparins/heparinoids and investigate enoxaparin at different stages of kidney dysfunction. Only controlled trials were considered, and the enoxaparin dose had to be specified. The clinical endpoint was defined as apparent major bleeding. Out of 1,027 publications, 20 studies met the criteria and were analyzed. Our meta-analysis shows that enoxaparin major bleeding complications at a GFR < 60 ml/min increase significantly, with a relative risk (RR) of 1.67 [95% confidence interval (CI) 1.12-2.50) compared with other anticoagulants (p = 0.01). RR for patients on enoxaparin therapy increases exponentially with each stage of chronic kidney disease (CKD stage 1-5) [RR = 0.585 x exp(0.524 x CKD)]. Despite dose adjustment, the major bleeding risk is still significantly increased in patients with a GFR < 60 ml/min versus those with a GFR > 60 ml/min. Only patients with a GFR > 60 ml/min can be safely treated with enoxaparin.