Abelacimab: A leap forward in anticoagulation with FXI and FXIa Inhibition.

Direct Oral Anticoagulants (DOACs) have revolutionized the treatment of thromboembolic disorders, offering targeted, effective, and safer alternatives to traditional anticoagulants like heparins and vitamin K antagonists (VKAs). Despite their benefits, DOACs have drawbacks, including an increased risk of gastrointestinal bleeding and unsuitability for patients with mechanical heart valves. Recent research has highlighted Factor XI (FXI) as a promising anticoagulation target due to its significant role in pathological thrombosis and minor involvement in normal hemostasis. Abelacimab, an antibody that inhibits FXI, has shown potential in transforming anticoagulation therapy by sparing hemostasis. This review provides a comprehensive analysis of abelacimab, examining its clinical pharmacology and its pharmacokinetic and pharmacodynamic properties. It scrutinizes abelacimab's safety profile and key monitoring parameters. The current evidence supporting its use and potential future research strengthening its position in anticoagulant therapy is also discussed. The objective is to enhance understanding and contribute to discussions around developing safer anticoagulants, particularly for patients at risk for thrombosis.

Comparison of Early Versus Late Adjunctive Vasopressin and Corticosteroids in Patients With Septic Shock.

BACKGROUND: Vasopressin (VP) and hydrocortisone (HC) have been shown to improve outcomes in patients with septic shock. However, there is very little literature addressing the impact of the timing of the combination. OBJECTIVE: This study was conducted to evaluate the impact of early versus late initiation of both VP and HC on time to shock reversal in septic shock patients. METHODS: This was a retrospective study conducted at a tertiary academic medical center. Data were collected from system-generated reports, which were used to identify patients with septic shock who were admitted to an intensive care unit (ICU) and received both VP and HC. The primary endpoint was time to shock reversal. Patients were divided into the "early" group if both VP and HC were initiated within 12 hours of vasopressor initiation or into the "late" group if either VP or HC (or both agents) were initiated after 12 hours of vasopressor initiation. RESULTS: A total of 122 patients were included in the analysis. Early initiation was associated with a shorter time to shock reversal (34 hours vs 65 hours; P = 0.012) compared to late initiation. There were no differences in ICU length of stay, mortality, the number patients requiring renal replacement therapy, or the duration of mechanical ventilation in either group. CONCLUSION AND RELEVANCE: Our study addressed a major gap in the literature and suggests that adding the combination of VP and HC within 12 hours of septic shock may be associated with improved patient outcomes.

Comparative Risk of Acute Kidney Injury Following Concurrent Administration of Vancomycin with Piperacillin/Tazobactam or Meropenem: A Systematic Review and Meta-Analysis of Observational Studies.

The study aims to comparatively assess the nephrotoxicity of vancomycin when combined with piperacillin-tazobactam (V + PT) or meropenem (V + M) in adult patients hospitalized in general wards or intensive care units. We searched MEDLINE, Google Scholar, and Web of Science for observational studies evaluating incidences of AKI in adult patients receiving V + PT or V + M for at least 48 h in general wards or intensive care units. The primary outcome was AKI events, while the secondary outcomes were hospital length of stay, need for renal replacement therapy (RRT), and mortality events. The odds ratio (OR), or mean difference for the hospital length of stay, with a corresponding 95% confidence interval (CI) from the inverse variance weighting random-effects model were estimated for the risk of AKI, RRT, and mortality. Of the 112 studies identified, twelve observational studies were included in this meta-analysis with a total of 14,511 patients. The odds of having AKI were significantly higher in patients receiving V + PT compared with V + M (OR = 2.31; 95%CI 1.69-3.15). There were no differences between V + PT and V + M in the hospital length of stay, RRT, or mortality outcomes. Thus, clinicians should be vigilant while using V + PT, especially in patients who are at high risk of AKI.

Real-World Effectiveness and Safety of Apixaban versus Warfarin in Patients with Acute Venous Thromboembolism: Experience of a Large Tertiary Hospital in Saudi Arabia.

PURPOSE: The main objective of this study was to evaluate the effectiveness and safety of apixaban versus warfarin in patients with venous thromboembolism (VTE) in a "real-world" setting. PATIENTS AND METHODS: A retrospective cohort study was conducted using data from a large tertiary hospital in Saudi Arabia. Patients were included if they were adults (≥18 years), diagnosed with VTE, and treated with either apixaban or warfarin between January 2016 and September 2018. Patients who had received anticoagulation therapy within three months of the date of the index event were excluded. The effectiveness outcomes were incidence of VTE recurrence (ie, deep vein thrombosis DVT or pulmonary embolism [PE]), while the safety outcome was incidence of any major bleeding (MB) event within 90 days of follow-up. RESULTS: Among the 492 patients included for study, 212 (43.1%) received apixaban and 280 (56.1%) received warfarin. The mean age of patients was 53.6±19.1 years and 62% of the cohort was female. Comparable rates of VTE recurrence were observed for apixaban and warfarin treatment groups during follow-up (adjusted odds ratio (AOR) =0.95; 95% CI 0.53-1.68), including DVT (AOR=1.06; 95% CI 0.52-2.17) and PE (AOR=0.78; 95% CI 0.31-1.96). However, apixaban was associated with significantly fewer MB events than warfarin (AOR=0.18; 95% CI 0.04-0.83). CONCLUSION: The use of apixaban for the treatment of Saudi patients with acute VTE is associated with a VTE recurrence rate comparable to that of warfarin, with significantly fewer MB events.

Safety and efficacy of dual versus triple antithrombotic therapy (DAT vs TAT) in patients with atrial fibrillation following a PCI: a systematic review and network meta-analysis.

OBJECTIVE: Creating an appropriate antithrombotic therapy for patients with atrial fibrillation (AF) who have undergone percutaneous coronary intervention (PCI) remains a dilemma. Several clinical trials compared the use of a dual antithrombotic therapy (DAT) regimen with a direct oral anticoagulants including (apixaban, dabigatran, edoxaban or rivaroxaban) and a P2Y12 inhibitor versus a triple antithrombotic therapy (TAT) that includes a vitamin K antagonist plus aspirin and a P2Y12 inhibitor in patients with AF who have undergone PCI. However, there are no head-to-head trials comparing the DAT regimens to each other. We aimed to compare the efficacy and safety of DAT regimens using a network meta-analysis (NMA) approach. DESIGN: A systematic review and NMA of randomised clinical trials. METHODS: We conducted a systematic literature review to identify relevant randomised clinical trials and performed a Bayesian NMA for International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant non-major (CRNM) bleeding, all-cause mortality, stroke, myocardial infarction (MI) and stent thrombosis outcomes. We used NetMetaXL V.1.6.1 and WinBUGS V.1.4.3 for the NMA and estimated the probability of ranking the treatments based on the surface under the cumulative ranking curve. RESULTS: The comparison between DAT regimens showed no significant difference in the safety or efficacy outcomes. Apixaban regimen was ranked first as the preferred therapy in terms of ISTH major or CRNM bleeding and stroke, with a probability of 52% and 54%, respectively. Rivaroxaban regimen was the preferred therapy in terms of MI and stent thrombosis, with a probability of 34% and 27%, respectively. Dabigatran regimen was ranked first in terms of all-cause mortality, with a probability of 28%. CONCLUSION: The DAT regimens are as safe and effective as TAT regimens. However, ranking probabilities for the best option in the selected outcomes can be used to guide the selection among these agents based on different patients' conditions.

Direct oral anticoagulants for the treatment of venous thromboembolism in patients with active malignancy: a systematic review and meta-analysis.

Low molecular weight heparins (LMWHs) are considered the standard of care for the treatment of venous thromboembolism (VTE) associated with cancer. We conducted a meta-analysis to evaluate the safety and efficacy of direct oral anticoagulants (DOACs) in patients with cancer. We systematically searched Medline for potential randomized-control clinical trials (RCTs) and post-hoc analyses. For each study, data on recurrent VTE, major or clinically relevant non-major bleeding (CRNMB), and major bleeding (MB) were extracted. Initially, a total of 1395 citations were identified. Eight studies met our eligibility criteria. The utilization of DOACs in patients with cancer showed a statistically significant reduction in the risk of VTE recurrence compared to LMWH or warfarin (RR = 0.64; 95% CI 0.46-0.88). Similar rates of major or CRNMB were observed between DOACs and LMWH or warfarin (RR = 1.00; 95% CI 0.75-1.33). There was no significant difference in the rate of MB between DOACs and LMWH or warfarin (RR = 1.31; 95% CI 0.71-2.44). Our results suggest that DOACs might reduce the incidence of VTE recurrence in patients with cancer without putting them at high risk for MB/CRNMB or MB. Our findings were mainly driven by the results of the Hokusai VTE Cancer trial. Given the level of investigated evidence, our findings should be interpreted with caution since the majority of the data were originated from sub-group analyses of large (RCTs). Future studies that are adequately powered are warranted to assess efficacy and safety data of DOACs for the treatment of VTE in patients with different types of cancer.