Search

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Dabigatran etexilate is an oral direct thrombin inhibitor used in preventing thromboembolism in patients with atrial fibrillation and several other conditions. Routine dabigatran concentration monitoring is not recommended in clinical practice; however, measurement of dabigatran concentration may be required in several conditions. This study aims to pool the peak and trough dabigatran concentration from real-world studies. A systematic review was performed to identify studies that measured the peak and trough dabigatran concentrations. Observational studies reporting dabigatran peak or trough concentrations and patients' clinical characteristics of either sex, age or weight were included. Random-effect meta-analyses and metaregression were conducted to pool dabigatran concentrations and to identify the correlation between factors affecting dabigatran concentrations. Fifteen studies with a total of 1226 patients were included. The pooled peak dabigatran concentration was 133 ng/mL (95% CI: 113-154, I 2  = 86%, n = 655), while the pooled dabigatran trough concentration was 80 ng/mL (95% CI: 69-91, I 2  = 93%, n = 1010). Metaregression analyses suggested that age is significantly correlated to trough concentration, while body weight and creatinine clearance significantly correlated to peak concentration. Subgroup results revealed that dabigatran concentration when measured with liquid chromatography-tandem mass spectrometry was higher than haemoclot thrombin inhibitor assay. Several guidelines have proposed dabigatran concentrations target range and the pooled dabigatran concentrations were in line with the suggested range. Further studies to correlate dabigatran concentrations and clinical outcomes is warranted to improve the safety and efficacy monitoring of dabigatran therapy., (© 2022 British Pharmacological Society.)

Background & Aims: Non-vitamin K antagonist oral anticoagulants (NOACs) are convenient and effective in the prevention and treatment of venous thromboembolism and the prevention of stroke in patients with atrial fibrillation. However, these drugs have been associated with an increased risk of gastrointestinal (GI) bleeding. We conducted a systematic review and meta-analysis to determine the risk of GI bleeding in patients receiving these drugs., Methods: We searched the EMBASE, Medline, Cochrane, and ISI Web of knowledge databases through January 2016 for randomized trials that compared NOACs with conventional anticoagulants for approved indications. We conducted a meta-analysis, reporting odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome was major GI bleeding. Secondary outcomes included clinically relevant nonmajor bleeding and upper and lower GI bleeding. We performed a priori subgroup analyses by individual drug., Results: Our analysis included a total of 43 randomized trials, comprising 166,289 patients. There was no difference between NOACs and conventional anticoagulants in the risk of major bleeding (1.5% vs 1.3%, respectively; OR, 0.98; 95% CI, 0.80-1.21), clinically relevant nonmajor bleeding (0.6% vs 0.6%, respectively; OR, 0.93; 95% CI, 0.64-1.36), upper GI bleeding (1.5% vs 1.6%, respectively; OR, 0.96; 95% CI, 0.77-1.20), or lower GI bleeding (1.0% vs 1.0%, respectively; OR, 0.88; 95% CI, 0.67-1.15). Dabigatran (2.0% vs 1.4%, respectively; OR, 1.27; 95% CI, 1.04-1.55) and rivaroxaban (1.7% vs 1.3%, respectively; OR, 1.40; 95% CI, 1.15-1.70) were associated with increased odds of major GI bleeding compared with conventional anticoagulation, whereas no difference was found for apixaban (0.6% vs 0.7%, respectively; OR, 0.81; 95% CI, 0.64-1.02) or edoxaban (1.9% vs 1.6%, respectively; OR, 0.93; 95% CI, 0.78-1.11). These subgroup findings were not observed in other sensitivity analyses., Conclusions: In a systematic review and meta-analysis, we found risk of major GI bleeding to be similar between NOACs and conventional anticoagulation. Dabigatran and rivaroxaban, however, may be associated with increased odds of major GI bleeding. Further high-quality studies are needed to characterize GI bleeding risk among NOACs., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

A best evidence topic was written according to a structured protocol. The question addressed was 'In patients requiring an implanted cardiac rhythm device, do novel oral anticoagulant agents lead to increased rates of peri-procedural complications?' Altogether 1228 papers were found using the reported search, of which 5 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The novel oral anticoagulant agents (NOACs) assessed in the included studies were dabigatran (a direct thrombin inhibitor) and rivaroxaban (a Factor Xa inhibitor). Dabigatran was included in all five studies and showed bleeding complication rates of 0-4%. Rivaroxaban was included in one study and had bleeding complication rates of 4%. Warfarin was a comparator agent in three studies and had bleeding complication rates of 4.6-8%. The incidence rate of thromboembolic complications was 0-1% with dabigatran and 0% with rivaroxaban and warfarin in all studies. Based on the available studies, there is no evidence of significantly increased risk of bleeding or thromboembolic events with NOACs compared with warfarin when used at the time of cardiac rhythm device implantation. However, not all patients in the studies were actually receiving the specified NOAC at the time of device implantation, thereby limiting the available evidence., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The Asian population with atrial fibrillation (AF) have a higher risk of stroke than the caucasian population and a higher risk of intracranial bleeding when anticoagulated with warfarin. There are few real-world studies comparing the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin among Asian patients to assess its outcomes of ischemic stroke and hemorrhagic stroke., Methods: A retrospective cohort study of 1000 patients on dabigatran and warfarin from 2009 to 2013., Results: Data were available for 500 patients on dabigatran and 500 patients on warfarin. The average follow-up duration was 315 ± 280 days in the dabigatran group and 355 ± 232 in the warfarin group. The time in therapeutic range (TTR) was 53.2% in the warfarin-treated group, with 32.8% of patients in the subtherapeutic international normalized ratio range of <2. None of the patients in the dabigatran group had ischemic cerebrovascular accident (CVA) compared to 4 (0.8%) patients in the warfarin group, hazard ratio (HR) 0.13, P = .3. There was 1 (0.2%) patient in both dabigatran and warfarin groups with hemorrhagic CVA (HR 1.16, P = .92). There were 3 (0.6%) patients with major bleeding in the dabigatran group compared to 2 (0.4%) patients in the warfarin group (HR 1.57, P = .59)., Conclusion: There were similar rates of efficacy for outcomes of ischemic CVA, hemorrhagic CVA, and bleeding when comparing dabigatran with warfarin. Our study shows that despite similar efficacy, suboptimal TTR rates and inconveniences with warfarin demonstrate that NOACs are preferred for stroke prevention in AF., (© The Author(s) 2015.)

The practice of outpatient general internal medicine requires a diverse and evolving knowledge base. General internists must identify practice-changing shifts in the literature and reflect on their impact. Accordingly, we conducted a review of practice-changing articles published in outpatient general internal medicine in 2014. To identify high-quality, clinically relevant publications, we reviewed all titles and abstracts published in the following primary data sources in 2014: New England Journal of Medicine, Journal of the American Medical Association (JAMA), Annals of Internal Medicine, JAMA Internal Medicine, and the Cochrane Database of Systematic Reviews. All 2014 primary data summaries from Journal Watch-General Internal Medicine and ACP JournalWise also were reviewed. The authors used a modified Delphi method to reach consensus on inclusion of 8 articles using the following criteria: clinical relevance to outpatient internal medicine, potential for practice change, and strength of evidence. Clusters of important articles around one clinical question were considered as a single-candidate series. The article merits were debated until consensus was reached on the final 8, spanning a variety of topics commonly encountered in outpatient general internal medicine., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Dabigatran, rivaroxaban, and apixaban have been approved for use in patients with atrial fibrillation based upon randomized trials demonstrating their comparable or superior efficacy and safety relative to warfarin. Little is known about their adoption into clinical practice, whether utilization is consistent with the controlled trials on which their approval was based, and how their use has affected health spending for patients and insurers., Methods: We used medical and prescription claims data from a large insurer to identify patients with nonvalvular atrial fibrillation who were prescribed an oral anticoagulant in 2010-2013. We plotted trends in medication initiation over time, assessed corresponding insurer and patient out-of-pocket spending, and evaluated the cumulative number and cost of anticoagulants. We identified predictors of novel anticoagulant initiation using multivariable logistic models. Finally, we estimated the difference in total drug expenditures over 6 months for patients initiating warfarin versus a novel anticoagulant., Results: There were 6893 patients with atrial fibrillation that initiated an oral anticoagulant during the study period. By the end of the study period, novel anticoagulants accounted for 62% of new prescriptions and 98% of anticoagulant-related drug costs. Female sex, lower household income, and higher CHADS2, CHA2DS2-VASC, and HAS-BLED scores were significantly associated with lower odds of receiving a novel anticoagulant (P <.001 for each). Average combined patient and insurer anticoagulant spending in the first 6 months after initiation was more than $900 greater for patients initiating a novel anticoagulant., Conclusions: This study demonstrates rapid adoption of novel anticoagulants into clinical practice, particularly among patients with lower CHADS2 and HAS-BLED scores, and high health care cost consequences. These findings provide important directions for future comparative and cost-effectiveness research., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The safety of recombinant tissue plasminogen activator (rt-PA) and/or endovascular therapy for patients using the novel oral anticoagulant (NOAC) for atrial fibrillation remains unclear., Methods: We report a patient who was treated by both rt-PA and endovascular thrombectomy who suffered from acute ischemic stroke under treatment with NOAC., Results: An 83-year-old woman had a medical history with ischemic stroke due to paroxysmal atrial fibrillation and was then administered 10 mg of rivaroxaban daily. Although she took rivaroxaban in the morning, ischemic stroke recurred at midnight of that day. Soon after transferring to our hospital, we confirmed right middle cerebral artery (MCA) occlusion in the patient and then initiated treatment with intravenous rt-PA. Although no hemorrhagic complication occurred, recovery of her symptoms was not seen, and endovascular thrombectomy was performed. Although the inferior branch of the MCA was recanalized, an infarct was seen in her left frontal lobe. Hemorrhagic transformation was not observed during or after these combined treatments., Conclusions: Thrombolysis and/or endovascular thrombectomy might be safe for patients treated with the new anticoagulant rivaroxaban., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Rivaroxaban is a novel anticoagulant approved for use in patients with atrial fibrillation for stroke prevention. It is a factor Xa inhibitor, and its activity cannot be monitored with use of the international normalized ratio. A 5.6% chance of major bleeding is associated with rivaroxaban use, including intracranial and gastrointestinal bleeds. We report the first case, to our knowledge, of isolated hemopericardium related to rivaroxaban use, which could potentially lead to death from cardiac tamponade. A 76-year-old man who was receiving rivaroxaban for atrial fibrillation presented to the emergency department with pleuritic chest pain and was found to have a hemopericardium. No signs of tamponade were evident, and his bleed remained stable after discontinuing rivaroxaban. The patient had also been taking saw palmetto, which may have contributed to the bleed by increasing rivaroxaban activity. A work-up for other causes of hemopericardium, including pacemaker lead misplacement and autoimmune disease-related pericarditis, was negative. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's development of hemopericardium and rivaroxaban use. This case highlights the potential for bleeding complications associated with novel anticoagulants. Herbal products and various drugs may increase rivaroxaban levels by inhibiting P-glycoprotein and cytochrome P450 3A4 activity. Clinicians should be aware of these potential interactions with rivaroxaban and perform a review of not only the patient's drug therapy but also any herbal and food products that could alter the levels of anticoagulants. The lack of an antidote and the inability to dialyze rivaroxaban is a significant concern in situations of life-threatening bleeds. A laboratory test for monitoring rivaroxaban levels may be required for its safe use., (© 2014 Pharmacotherapy Publications, Inc.)

Until lately warfarin was the only valuable oral anticoagulant in stroke reduction in high risk cases with non valvular atrial fibrillation (NVAF). Although with warfarin the rate of stroke reduced notably, the major concern is the risk of serious bleeding and difficulty of establishing and maintaining the international normalised ratio (INR) within the therapeutic range. With the development of the novel anticoagulants we now have for the first time since the innovation of Warfarin feasible alternatives to it to decrease stroke rates in high risk patients with NVAF. To diminish adverse bleeding events with the novel anticoagulant proper selection of patients prior starting treatment is essential., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)