Oral Anticoagulants For Prevention Research Articles

Beyond Anticoagulation: Limitations of Oral Anticoagulants in Preventing Stroke Recurrence in Atrial Fibrillation

Background/Objectives: Despite the widespread use of oral anticoagulants (OACs), acute ischemic stroke (AIS) remains a significant risk for patients with atrial fibrillation (AF). The real-world effectiveness of OACs in preventing recurrent strokes, particularly following an initial stroke of cardioembolic (CE) origin, continues to be a major challenge for clinicians managing AF patients. This study evaluated the efficacy of OACs in secondary stroke prevention and investigated the influence of anticoagulation type and quality on recurrence risk. Methods: We analyzed data from 128 AF patients in the prospective Transzlációs Idegtudományi Nemzeti Laboratórium (TINL) STROKE-registry, admitted with CE stroke between February 2023 and September 2024. Patients were categorized by anticoagulation status at admission (OAC-users, n = 89; anticoagulation-naïve, n = 39). Recurrence rates were assessed using logistic regression models, adjusted for age, sex, hypertension, diabetes, and pre-stroke disability. Subgroup analyses explored the effects of anticoagulation type and quality. Results: Recurrence rates were similar between the OAC-treated and anticoagulation-naïve patients after adjusting for confounders (19.10% vs. 17.95%, p = 0.870). Among the anticoagulated patients, neither anticoagulation type nor quality alone significantly influenced the recurrence risk. However, their interaction was statistically significant (p = 0.049), suggesting that the effectiveness of anticoagulation in preventing strokes is strongly affected by treatment quality. Conclusions: Although OACs are a cornerstone of stroke prevention in patients with AF, their efficacy in reducing recurrence depends on optimal management. These findings highlight that adequate anticoagulation, not just its use, is critical to minimize recurrence risk. To effectively prevent strokes in high-risk AF patients, future strategies must focus on standardized protocols, tailored monitoring, and individualized dosing regimens.

Cost-effectiveness analysis of apixaban compared to other direct oral anticoagulants for prevention of stroke in Austrian atrial fibrillation patients

ABSTRACT Objectives Several direct oral anticoagulants (DOACs) have been approved by the European Medicines Agency since 2008. The aim of the present cost-effectiveness-analysis was to analyze apixaban compared to other DOACs and vitamin K antagonists (warfarin) in Austria. Methods A cost-utility-model was developed to simulate lifetime-costs and quality-adjusted-life-years of DOACs and warfarin, based on a published Markov-Model and 23 randomized trials with 94,656 atrial-fibrillation (AF) patients. Each year, a patient has a probability of suffering a clinically relevant (extracranial) bleed, an intracranial hemorrhage (ICH), an ischemic stroke or a myocardial infarction (MI), remaining healthy, or deceasing. Direct-costs (2018€) were derived from published sources from the payer’s perspective. Results In the base-case, warfarin had the lowest cost of 12,968 € (95%-CI±593 €) followed by apixaban (15,269 €±661 €), edoxaban (15,534 €±641 €), dabigatran (15,687 €±667 €), and rivaroxaban (17,522 €±764 €). Apixaban had the highest quality-adjusted-life-years estimate at 5.45 (SD, 0.06). In a Monte-Carlo probabilistic sensitivity analysis, apixaban was cost-effective vs. edoxaban, dabigatran, warfarin, and rivaroxaban in 85.6%, 79.0%, 76.4%, and 61.2% of the simulations, respectively. Conclusion In patients with AF and an increased risk of stroke, prophylaxis with apixaban was highly cost-effective from the perspective of the Austrian health-care system.

Atrial Fibrillation and Diabetes Mellitus: the Control of Thromboembolic Risk

Atrial fibrillation is one of the most common concomitant diseases in patients with diabetes mellitus (DM). Meta-analyses of multiple studies have shown that the risk of AF is higher for diabetic patients with impaired glucose homeostasis than for patients without DM. Patients with AF and DM were younger, more frequently had arterial hypertension, chronic kidney disease, heart failure, and ischemic heart disease, and stroke and were characterized with a more severe course of AF. The article discusses possible mechanisms of the mutually aggravating effects of DM and AF, scales for evaluating the risk of bleeding (CHADS2, CHA2DS2‑VASc, HAS-BLED), and the role of anticoagulants. A meta-analysis of 16 randomized clinical studies, including 9 874 patients, has demonstrated the efficacy of oral anticoagulants in prevention of stroke with an overall decrease in the relative risk by 62 % compared to placebo (95% confidence interval, from 48 to 72 ). For prevention of complications in patients with AF and DM, current antithrombotic therapies can be used, specifically the oral factor Xa inhibitor, rivaroxaban, which is the best studied in patients with AF and DM and represents a possible alternative to warfarin in such patients.

Interest of direct oral anticoagulants in prevention of stroke in young subject with atrial vulnerability

Despite the recently described new syndromes, about a third of ischemic stroke (aic) in young adults remains unexplained. The role of atrial vulnerability (va), was suggested as substratum of paroxysmal atrial fibrillation (paf); we studied prospectively in 121 young patients with ischemic stroke. The aims of this study is to search recurrence of stroke for patients with atrial vulnerabilities requiring direct oral anticoagulant therapy for prevention vs patients without atrial vulnerabilities. Patients 17 to 55 victims admitted for ischemic stroke. An electrophysiological study was performed in case of unknown etiology, within 90 days after ischemic stroke. In addition to the usual parameters were measured conduction time intra atrial refractory periods, latent vulnerability index, prior to the completion of atrial stimulation Programmed. A total of 53 patients with VA+ and, two groups of patients were formed: the first group (27 patients) VA+ was treated with DOA (rivaroxaban), and (26 patients) VA+ were not treated and followed for 06 months. A total of 121 patients, mean age 40.89 years, sex ratio 1.63: 53 (43.8%) had a positive atrial vulnerability. There is no evidence of significant difference in the type and location of the AIC, with a significant difference against tobacco (risk = 2.4), birth control pills (risk = 3.6), the presence > 70 esa on holter ECG (risk = 3.7) and septal defects (pfo and/or asia with a risk = 2.89). On a mean follow up of 06 months, 04 (17%) patients presented with cerebral embolic recurrence in the group without DOA, and 00 patients in the VA+ group with DOA. With a sensitivity of 83% and a specificity of 61% and a negative predictive value of 97%; The presence of atrial vulnerability with a pathological ECG Holter (esa) exposed to a high risk of recurrence and embolic requiring antiarrhythmic therapy and discussion of anticoagulant treatment, specially with DOA.

Atrial Fibrillation, Type 2 Diabetes, and Non–Vitamin K Antagonist Oral Anticoagulants

ImportanceAtrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a 5-fold increase in the risk for stroke. Type 2 diabetes is an independent risk factor for both stroke and atrial fibrillation, and in the setting of AF, type 2 diabetes is independently associated with a 2% to 3.5% increase in absolute stroke rate per year. The overlap in the pathophysiologies of AF and type 2 diabetes are not well understood, and current practice guidelines provide few recommendations regarding patients with both conditions.ObservationsIn this article, we review the epidemiology and pathophysiology of the nexus of AF and type 2 diabetes. Furthermore, we analyze the subgroup of patients with type 2 diabetes enrolled in phase 3 clinical trials of non–vitamin K antagonist oral anticoagulants in prevention of arterial thromboembolism in AF, highlighting the greater absolute benefit of non–vitamin K oral anticoagulants in patients with type 2 diabetes. Finally, we offer recommendations on risk stratification and therapy for patients with concomitant AF and type 2 diabetes.Conclusions and RelevanceWe highlight the increased thromboembolic risk with coexisting AF and type 2 diabetes. We recommend that further studies be done to evaluate the potential benefits of anticoagulation for all patients who have both and the potential for non–vitamin K oral anticoagulants to have greater benefits than risks over vitamin K antagonists.

Meta-analysis and adjusted indirect comparison of direct oral anticoagulants in prevention of acute limb ischemia in patients with atrial fibrillation

Background: Direct oral anticoagulants are being presented as alternatives to warfarin for preventing stroke in patients with atrial fibrillation. Yet direct comparative trials between these agents in prevention of acute limb ischemia (ALI) are unavailable so far. Objective: To conduct an adjusted indirect comparison meta-analysis between direct oral agents for prevention of acute limb ischemia in atrial fibrillation. Methods: We conducted a systematic literature review searching electronic databases (MEDLINE and Embase) and the Cochrane Library from January 1990 through November 2014. Two blinded investigators reviewed all potentially relevant articles in a parallel manner by using a priori defined criteria. To assess the long-term efficacy and safety of these agents, only randomized clinical trials (RCTs) with follow-up durations of >1 year were included. The primary efficacy outcome was the end point of acute limb ischemia and/or extremity embolism. Results: A total of 44,563 patients from three RCTs met criteria for inclusion. Patients randomized to direct oral anticoagulants had a non-significant decreased risk for acute limb ischemia (risk ratio [RR]: 0.57, 95% confidence interval [CI]: 0.26–1.2). In the analysis between agents, however, rivaroxaban significantly lowered the risk of ALI compared to warfarin (RR: 0.23, 95% CI: 0.064–0.82), apixaban (RR: 0.26, 95% CI: 0.081–0.83), and dabigatran (RR: 0.24, 95% CI: 0.077–0.83). Conclusions: Significant differences in prevention of acute limb ischemia may exist between oral anticoagulant agents in patients with atrial fibrillation. Rivaroxaban lowers the risk of limb embolism versus warfarin, apixaban and dabigatran.

Positioning the New oral Anticoagulants for prevention of stroke in patients with non-valvular atrial fibrilation

Positioning the New oral Anticoagulants for prevention of stroke in patients with non-valvular atrial fibrilation

Orale Antikoagulation bei Vorhofflimmern

The correct oral anticoagulation for prevention of thromboembolic events in patients with atrial fibrillation and a corresponding risk profile is essential. However, anticoagulation is not carried out according to the guidelines in all patients. The direct oral anticoagulants (DOACs) are a new treatment alternative to vitamin K antagonists. The new guidelines of the European Society of Cardiology (ESC), recent study results and the practice guidelines of the European Heart Rhythm Association (EHRA) can help to use DOACs appropriately, to optimize the prevention of thromboembolic events in patients with atrial fibrillation and to reduce complications.

Dabigatran - A New Chapter in Anticoagulation

For the last 60 years warfarin has been the cornerstone for chronic anticoagulation in prevention of ischemic strokes and systemic embolization. Warfarin therapy has several limitations including frequent monitoring and various food and significant drug interactions, which make it a less than ideal chronic oral anticoagulant. The continued search for safe, effective, medications with predictable pharmacokinetic profiles has led to newer alternatives. Dabigatran is a potent reversible, competitive direct thrombin inhibitor which is available as the prodrug, Dabigatran etexilate. It was first approved in Europe and recently in October 2010, the US food and drug administration (FDA) has approved the use of this novel oral anticoagulation for prevention of stroke in those with non valvular atrial fibrillation. This review will cover the chemical structure, mechanism of action, pharmacokinetic profile, clinical trials, dosage, clinical implication and adverse effects of dabigatran.

Welcome to Clinical Investigation

The clinical development of a new therapeutic agent is a long and complex process that begins with the translation of basic science and preclinical data to potential applications in humans, followed by the design and conduct of clinical trials, the evaluation and publication of results, and continuing through the regulatory approval process and postmarketing surveillance. Those who are involved at any level of drug development are familiar with the immense opportunities and the many challenges of such an undertaking. The total cost of bringing a new drug to market can be as high as US$1.3 billion, with much of this incurred during clinical evaluation; only one of every 10,000 potential medicines survives the development and approval process. To optimize the probability of success in this increasingly globalized endeavor, it is essential that stakeholders in many disciplines have an easily accessible platform for rapid and effective communication. This is an introduction to the first issue of a journal intended fill this need. It is my great pleasure to welcome you to Clinical Investigation. This is an international forum for communicating and evaluating the vast amount of information associated with the clinical development of new therapeutic agents. Journal coverage will include all areas of therapy with drugs ranging from conventional small molecules to biotech-derived compounds such as vaccines, monoclonal antibodies, recombinant proteins, antisense, cell and gene therapies. We publish original research, review articles, perspectives, commentaries, debates of controversial issues and more. In order to assure high-quality content, manuscripts submitted to Clinical Investigation are rigorously vetted through a systematic peer-review process. The intended audience for Clinical Investigation includes clinical investigators, clinicians, healthcare policy makers, drug formulary managers, healthcare statisticians, healthcare economists, regulatory affairs personnel and others involved in the design and conduct of clinical trials. Specific types of manuscripts that will be considered for publication are overviews of the clinical progress of new drugs, drug classes and therapeutic areas; reports of Phase I to IV clinical trials; healthcare outcomes and pharmacoeconomics; clinical trial design and methodology; commentary on trials in progress; practical aspects of clinical research; drug safety issues and adverse event monitoring; the use of biomarkers in clinical trials; regulatory issues; and clinical trial data management and ana lysis. If you have clinical research information that you would like to share with colleagues worldwide, consider submitting your manuscript to Clinical Investigation. If you wish to stay informed on new developments in clinical research, become a regular reader. The globalization of clinical trials is addressed in this inaugural issue through viewpoints on developing an international network for clinical research with community-acquired pneumonia [1]. Novel new and emerging oral anticoagulants for prevention of stroke in patients with atrial fibrillation are reviewed by Weitz and Eikelboom [2]. Perspectives on new drug development are addressed in the pitfalls and progress of early-phase oncology clinical trial design [3] and the potential impact of neoadjuvant trials on clinical practice [4]. Clinical trial outcomes include data on pazopanib for renal cell carcinoma [5], and lacosamide for partial-onset seizures [6] “... it is essential that stakeholders in many disciplines have an easily accessible platform for rapid and effective communication.”

Novel antithrombotic agents: indirect synthetic inhibitors of factor Xa and direct thrombin inhibitors. Evidences from clinical studies.

The optimal drugs employed in the antithrombotic treatment and prophylaxis have ideally been suggested to have high efficacy and safety and to be easy to use as regards the administration route and the fashion of monitoring the anticoagulant effect. A number of agents are under development in order to improve such requirements. Among them, the present review is focussed on a selective factor Xa inhibitor (pentasaccharide fondaparinux) and the direct thrombin inhibitors now available on a clinical ground. Fondaparinux is the first of a new class of selective antithrombin-dependent factor Xa inhibitors; it does not interact with plasma proteins other than antithrombin, leading to a predictable pharmacokinetics, which renders monitoring and dose adjustment unnecessary. The efficacy and safety of fondaparinux has been assessed in a number of clinical trials. In patients undergoing major orthopaedic surgery, a 2.5 mg s.c administration once daily induced a 50% average relative risk reduction for overall venous thromboembolism in comparison with enoxaparin but also an increased rate of major bleeding. Parenteral direct thrombin inhibitors include hirudin, bivalirudin and argatroban. these inhibitors have been studied in patients with coronary heart disease. In particular, in patients undergoing percutaneous coronary interventions, bivalirudin showed equivalent or higher efficacy but lower bleeding in comparison with unfractionated heparin. Another series of molecules capable of inhibiting thrombin is derived from the site of fibrinogen to which thrombin binds. Inogatran and melagatran have a low bioavailability when given orally, whereas the chemically modified prodrug ximelagatran has a higher bioavailability. Ximelagatran is safe and effective at least as low molecular weight heparin in patients undergoing major orthopaedic surgery and is safe and effective also in prevention of recurrence in patients with venous thromboembolism or myocardial infarction; ximelagatran is more effective than oral anticoagulants in prevention of arterial embolism due to atrial fibrillation, with comparable safety.

Trial finds that enoxaparin may be the preferred drug for initiating anticoagulation in atrial fibrillation*1Abstracted from: Stellbrink C, Nixdorff U, Hofmann T, et al. Safety and efficacy of enoxaparin compared with unfractionated heparin and oral anticoagulants for prevention of thromboembolic complications in cardioversion of nonvalvular atrial fibrillation: The Anticoagulation in Cardioversion using Enoxaparin (ACE) Trial. Circulation 2004; 109: 997-1003.

Trial finds that enoxaparin may be the preferred drug for initiating anticoagulation in atrial fibrillation*1Abstracted from: Stellbrink C, Nixdorff U, Hofmann T, et al. Safety and efficacy of enoxaparin compared with unfractionated heparin and oral anticoagulants for prevention of thromboembolic complications in cardioversion of nonvalvular atrial fibrillation: The Anticoagulation in Cardioversion using Enoxaparin (ACE) Trial. Circulation 2004; 109: 997-1003.

Safety and efficacy of enoxaparin compared with unfractionated heparin and oral anticoagulants for prevention of thromboembolic complications in cardioversion of nonvalvular atrial fibrillation: the Anticoagulation in Cardioversion using Enoxaparin (ACE) Trial

Safety and efficacy of enoxaparin compared with unfractionated heparin and oral anticoagulants for prevention of thromboembolic complications in cardioversion of nonvalvular atrial fibrillation: the Anticoagulation in Cardioversion using Enoxaparin (ACE) Trial