UNASSIGNED: With the increasing cases of TBI cases in the elderly population taking anticoagulants for comorbidities, there is a need to better understand the safety of new anticoagulants and how to manage anticoagulated TBI patients.
UNASSIGNED: A meta-analysis using a random-effect model was conducted to compare the effect of preinjury use of DOACs and VKAs on the outcomes following TBI.
UNASSIGNED: From 1951 studies, 49 studies with a total sample size of 15,180 met our inclusion criteria. Our meta-analysis showed no difference between preinjury use of DOACs or VKAs on ICH progression, in-hospital delayed ICH, delayed ICH at follow-up, and in-hospital mortality, but using DOACs was associated with a lower risk of immediate ICH (OR = 0.58; 95% CI = [0.42; 0.79]; p < 0.01) and neurosurgical interventions (OR = 0.59; 95% CI = [0.42; 0.82]; p < 0.01) compared to VKAs. Moreover, patients on DOACs experienced shorter length of stay in the hospital than those on VKAs (OR = -0.42; 95% CI = [-0.78; -0.07]; p = 0.02).
UNASSIGNED: We found a lower risk of immediate ICH and surgical interventions as well as a shorter hospital stay in patients receiving DOACs compared to VKA users before the head injury.

The best management of patients who suffer from traumatic brain injury (TBI) while on oral anticoagulants is one of the most disputed problems of emergency services. Indeed, guidelines, clinical decision rules, and observational studies addressing this topic are scarce and conflicting. Moreover, relevant issues such as the specific treatment (and even definition) of mild TBI, rate of delayed intracranial injury, indications for neurosurgery, and anticoagulant modulation are largely empiric. We reviewed the most recent evidence on these topics and explored other clinically relevant aspects, such as the promising role of dosing brain biomarkers, the strategies to assess the extent of anticoagulation, and the indications of reversals and tranexamic acid administration, in cases of mild TBI or as a bridge to neurosurgery. The appropriate timing of anticoagulant resumption was also discussed. Finally, we obtained an insight into the economic burden of TBI in patients on oral anticoagulants, and future directions on the management of this subpopulation of TBI patients were proposed. In this article, at the end of each section, a \"take home message\" is stated.

UNASSIGNED: To compare the predictive performance of CHA2DS2-VASc and HAS-BLED scores in atrial fibrillation (AF) patients with and without cancer.
UNASSIGNED: Using data from the Clinical Practice Research Datalink in England, we performed a retrospective cohort study of patients with new diagnoses of AF from 2009 to 2019. Cancer was defined as history of breast, prostate, colorectal, lung, or haematological cancer. We calculated the CHA2DS2-VASc and HAS-BLED scores for the 1-year risk of stroke and major bleeding events. Scores performance was estimated by discrimination [area under the receiver operating characteristic curve (AUC)] and calibration plots. Of 141 796 patients with AF, 10.3% had cancer. The CHA2DS2-VASc score had good to modest discrimination in prostate cancer AUC = 0.74 (95% confidence interval: 0.71, 0.77), haematological cancer AUC = 0.71 (0.66, 0.76), colorectal cancer AUC = 0.70 (0.66, 0.75), breast cancer AUC = 0.70 (0.66, 0.74), and lung cancer AUC = 0.69 (0.60, 0.79), compared with no-cancer AUC = 0.73 (0.72, 0.74). HAS-BLED discrimination was poor in prostate cancer AUC = 0.58 (0.55, 0.61), haematological cancer AUC = 0.59 (0.55, 0.64), colorectal cancer AUC = 0.57 (0.53, 0.61), breast cancer AUC = 0.56 (0.52, 0.61), and lung cancer AUC = 0.59 (0.51, 0.67), compared with no-cancer AUC = 0.61 (0.60, 0.62). Both the CHA2DS2-VASc score and HAS-BLED score were well calibrated across all study cohorts.
UNASSIGNED: Amongst certain cancer cohorts in the AF population, CHA2DS2-VASc performs similarly in predicting stroke to AF patients without cancer. Our findings highlight the importance of cancer diagnosis during the development of risk scores and opportunities to optimize the HAS-BLED risk score to better serve cancer patients with AF.

OBJECTIVE: Oral anticoagulants (OACs) reduce the risk of ischemic stroke but may increase the risk of major bleeding in patients with non-valvular atrial fibrillation (NVAF). Various risk scores, such as HAS-BLED, ATRIA, ORBIT, and DOAC, have been proposed to assess the risk of major bleeding in patients with NVAF receiving OACs. However, limited data are available regarding bleeding risk stratification in Japanese patients with NVAF.
METHODS: Of the 16,098 NVAF patients from the J-RISK AF study, the combined data of the five major AF registries in Japan (J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry), we analyzed 11,539 patients receiving OACs (median age, 71 years old; women, 29.6%; median CHA2DS2-VASc score, 3).
RESULTS: During the 2-year follow-up period, major bleeding occurred in 274 patients (1.3% per patient-year). In a multivariate Cox proportional hazards analysis, an advanced age, hypertension (systolic blood pressure ≥ 150 mmHg), bleeding history, anemia, thrombocytopenia, and concomitant antiplatelet agents were significantly associated with a higher incidence of major bleeding. We developed a novel risk stratification system, HED-[EPA]2-B3 score, which had a better predictive performance for major bleeding (C-statistics 0.67, [95% confidence interval, 0.63-0.70]) than the HAS-BLED (0.64, [0.60-0.67], P for difference 0.02) and ATRIA (0.63, [0.60-0.66], P for difference ＜0.01) scores. Furthermore, it was non-significantly higher than the ORBIT (0.65, [0.62-0.68], P for difference 0.07) and DOAC (0.65, [0.62-0.68], P for difference 0.17) scores.
CONCLUSIONS: Our novel risk stratification system, the HED-[EPA]2-B3 score, may be useful for identifying Japanese patients receiving OACs at a risk of major bleeding.

暂无摘要。

UNASSIGNED: While treatment interruption of non-vitamin K antagonist oral anticoagulants (NOACs) for elective surgery or procedures among patients with atrial fibrillation (AF) is becoming more prevalent, there remains insufficient evidence regarding the optimal perioperative management of NOACs, particularly procedures with minor bleeding risks.
UNASSIGNED: This study aims to evaluate the safety and effectiveness of a simplified, standardized protocol for perioperative management of direct factor Xa inhibitors in patients, with AF undergoing procedures associated with minor bleeding risk.
UNASSIGNED: This multicenter, prospective single-arm registry study plans to enroll patients undergoing procedures with minor bleeding risk who were prescribed direct factor Xa inhibitors for AF. The procedures with minor bleeding risk will include gastrointestinal endoscopy for diagnostic purposes, selected dental procedures, and ocular surgery for cataracts or glaucoma. For apixaban, patients will withhold the last evening dose and resume either from the evening dose of the procedure day or the following morning, depending on the bleeding risk of the patient. For edoxaban or rivaroxaban, patients will withhold only a single dose on the procedure day. The primary outcome is the occurrence of major bleeding events within 30 days. Secondary outcomes include systemic thromboembolism, all-cause mortality, and a composite of major and clinically relevant non-major bleeding events.
UNASSIGNED: This study has the potential to generate evidence regarding the safety of perioperative management for patients, with AF undergoing procedures associated with minor bleeding risk.
UNASSIGNED: Clinicaltrials.gov: NCT05801068.

OBJECTIVE: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear.
RESULTS: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005).
CONCLUSIONS: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.

Background: Toxicity or treatment failure related to drug-drug interactions (DDIs) are known to significantly affect morbidity and hospitalization rates. Despite the availability of numerous databases for DDIs identification and management, their information often differs. Oral anticoagulants are deemed at risk of DDIs and a leading cause of adverse drug events, most of which being preventable. Although many databases include DDIs involving anticoagulants, none are specialized in them. Aim and method: This study aims to compare the DDIs information content of four direct oral anticoagulants and two vitamin K antagonists in three major DDI databases used in Switzerland: Lexi-Interact, Pharmavista, and MediQ. It evaluates the consistency of DDIs information in terms of differences in severity rating systems, mechanism of interaction, extraction and documentation processes and transparency. Results: This study revealed 2\'496 DDIs for the six anticoagulants, with discrepant risk classifications. Only 13.2% of DDIs were common to all three databases. Overall concordance in risk classification (high, moderate, and low risk) was slight (Fleiss\' kappa = 0.131), while high-risk DDIs demonstrated a fair agreement (Fleiss\' kappa = 0.398). The nature and the mechanism of the DDIs were more consistent across databases. Qualitative assessments highlighted differences in the documentation process and transparency, and similarities for availability of risk classification and references. Discussion: This study highlights the discrepancies between three commonly used DDI databases and the inconsistency in how terminology is standardised and incorporated when classifying these DDIs. It also highlights the need for the creation of specialised tools for anticoagulant-related interactions.

BACKGROUND: Metabolism of oral anticoagulants (OAC) is affected by P-glycoprotein (P-gp)/ CYP3A4 enzyme. However, the P-gp/CYP3A4 inhibitors are unavoidably used with OACs.
METHODS: Medline, Cochrane, and Embase were systematically searched for randomized controlled trials and cohort studies from inception till 23rd November, 2022 to assess the safety and effectiveness of OACs when concomitantly used with P-gp/CYP3A4 inhibitors. The primary outcomes were major bleeding and gastrointestinal (GI) bleeding. Secondary outcomes were stroke/systemic embolism (SE), all-cause mortality, any bleeding as well as intracranial hemorrhage (ICH). We estimated summary odds ratios (OR) with 95% credible intervals (CI) using pairwise and network meta-analysis with random effects.
RESULTS: A total of 11 studies involving 37,973 patients were included. When concomitantly used with P-pg/ CYP3A4 inhibitors, network meta-analysis indicated that dabigatran, apixaban, and edoxaban were associated with significantly lower risk of major bleeding compared to rivaroxaban, with ORs of 0.56, 0.51 and 0.48, respectively. Rivaroxaban and dabigatran were associated with a significantly increased risk of GI bleeding than warfarin, apixaban and edoxaban. Dabigatran and apixaban were linked with significantly lower risk of any bleeding compared with warfarin (ORs were 0.75 and 0.68, respectively) or rivaroxaban (ORs were 0.67 and 0.60, respectively). Apixaban (OR 0.32) and edoxaban (OR 0.35) were associated with a lower risk of ICH compared with warfarin. There was no difference between any OACs in terms of stroke/SE or all-cause mortality.
CONCLUSIONS: When concomitantly used with P-gp/CYP3A4 inhibitors, apixaban and edoxaban were associated with a lower risk of bleeding, though no significant difference in effectiveness was observed among all OACs.

Tissue plasminogen activator (TPA) is indicated as an empiric therapy for refractory out-of-the-hospital cardiac arrest for suspected pulmonary embolism and myocardial infarction. Intracranial hemorrhage following TPA administration is a rare complication resulting in increased morbidity and mortality. A history of intracranial bleed, oral anticoagulant use prior to hospital admission, low body weight, and unstable hypertension with blood pressure above 180/110 mmHg at the time of presentation are associated with intracranial bleeding following tPA administration. Dedicated imaging including a Computed Tomography of the head without contrast, while feasible for patients presenting with acute stroke, is impractical in the setting of cardiac arrest. Here we report a case of 66 years old patient who presented in context of refractory cardiac arrest with recurrent PEAs with interval return of spontaneous circulation (ROSC) and was given tPA with eventual ROSC. He was subsequently found to have both a subarachnoid and intraventricular hemorrhage.