Apixaban For Stroke Prevention Research Articles

Milvexian vs apixaban for stroke prevention in atrial fibrillation: The LIBREXIA atrial fibrillation trial rationale and design

Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk. LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years. The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter. ClinicalTrials.gov NCT05757869.

Exploring the therapeutic utility of the factor XIa inhibitor asundexian.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Factor XIa inhibitors are a promising novel class of anticoagulants that attenuate pathological thrombosis with minimal interference with hemostasis. These effects contrast with those of conventional anticoagulants, which may exhibit adverse events of untoward bleeding precluding treatment in some patients. A variety of investigational pharmacological modalities have been developed and studied to target factor XIa. Asundexian is a small molecule inhibitor of factor XIa that has been evaluated in several clinical studies. It has been studied as an oral, once-daily medication and found to inhibit approximately 90% of factor XIa activity at doses of 20 to 50mg. Phase 2 trials have demonstrated the potential for improved safety compared to standard of care in certain treatment settings, such as in atrial fibrillation. For other indications, such as noncardioembolic stroke and acute myocardial infarction, asundexian has been used in addition to background antiplatelet therapy. In these instances, asundexian did not show a difference in the incidence of bleeding events compared to placebo. Phase 3 trials have recently been launched; however, the OCEANIC-AF trial was prematurely discontinued due to inefficacy of asundexian vs apixaban for stroke prevention in atrial fibrillation. Another phase 3 trial, OCEANIC-AFINA, is planned to compare asundexian to placebo in patients with atrial fibrillation at high risk for stroke who are deemed ineligible for anticoagulation.

Apixaban for stroke prevention in hemodialysis patients with nonvalvular atrial fibrillation

Apixaban for stroke prevention in hemodialysis patients with nonvalvular atrial fibrillation

Reduced dose, but not reduced risk: rates of inappropriate apixaban dose reduction and stroke and bleeding incidence

Abstract Introduction Patients with atrial fibrillation (AF) should be prescribed standard-dose (5mg twice daily) apixaban for stroke prevention unless they meet 2 or more criteria: age ≥80, weight ≤60kg, and/or creatinine ≤1.5mg/dL, in which case a reduced-dose (2.5mg twice daily) is indicated. Despite this, some clinicians may also prescribe reduced-dose apixaban to patients who do not meet criteria for dose reduction, in an effort to reduce bleeding risk. Purpose To assess apixaban prescribing patterns in patients with AF based on dose reduction criteria and to characterize baseline demographics and incidence of ischemic stroke, major bleeding, and intracranial hemorrhage (ICH) for patients stratified by standard-dose, appropriately reduced-dose, and inappropriately reduced-dose apixaban. Methods Using pooled data from 8 large hospitals in PCORnet, a multicenter national healthcare research network, we assessed the standard and reduced-dose apixaban prescribing patterns for patients with AF, with additional stratification of patients prescribed 2.5mg based on presence or absence of 2+ criteria for dose reduction. We then assessed baseline characteristics and 5-year event rate of ischemic stroke, major bleeding, ICH and death. Results Of 45,947 patients with AF on apixaban and available dosing information, 38,861 (85%) were prescribed apixaban 5mg and 7086 (15%) were prescribed 2.5mg. Of patients prescribed apixaban 2.5mg, 4321 (61%) did not meet criteria for dose reduction. Patients on reduced dose apixaban were more likely to be female and have comorbidities such as heart failure, hypertension, and prior ischemic stroke. These trends were more pronounced for patients meeting dose adjustment criteria than those not meeting criteria (Table 1). Unadjusted analyses found patients on 2.5mg of apixaban were significantly more likely to experience ischemic stroke, major bleeding, and all-cause death. Patients with 2+ dose reduction criteria on 2.5mg of apixaban had the highest rates of each event, but patients who were prescribed reduced dose without meeting criteria were also at elevated risk (Table 2). Conclusion Many patients prescribed reduced-dose apixaban do not meet criteria for dose reduction. Because patients prescribed reduced dose apixaban are older and have more cardiovascular risk factors, their incidence of stroke, major bleeding, and death exceeds that of full dose treated patients. These risks exist both for patients who do and do not meet criteria for dose reduction, suggesting potential under-treatment for the majority of dose-reduced patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer

EP News: Allied Professionals

Ray et al (JAMA 2021;326:2395–2404, PMID 34932078) sought to assess the rates of ischemic and hemorrhagic events in patients with atrial fibrillation (AF) who were newly prescribed either rivaroxaban or apixaban for stroke prevention. Using an established Medicare database with de-identified data, patients were included if they had Medicare A or B plus prescription plan D and were >65 years old, had a complete set of data, and had a new prescription for rivaroxaban or apixaban prescribed for AF between January 1, 2013, and November 30, 2018.

Apixaban for Stroke Prevention in Atrial Fibrillation: Why are Event Rates Higher in Clinical Practice than in Randomized Trials?-A Systematic Review.

Recent reports suggest an important contribution from frequent off-label use of apixaban 2.5 mg twice daily to the higher rates of thromboembolic events observed in observational studies (OSs) relative to in randomized controlled trials (RCTs), and consequently, advocate against such use in all patients. To examine factors contributing to the higher thromboembolic event rates, we estimated the prevalence of off-label use in contemporary practice, and compared patient characteristics and rates of stroke/systemic embolism, major bleeding, and mortality by apixaban dose and by study design in a systematic review and meta-analysis. We identified 18 OSs and 2 RCTs that included 155,228 and 11,928 patients, respectively. Patients in OSs more often received apixaban 2.5 mg twice daily (31.3% vs. 5.1%), were older (mean age 73.8 vs. 69.8 years), and had higher CHA2DS2-VASc scores (mean 3.6 vs. 2.9) versus those in RCTs. We observed a consistent pattern of higher rates of thromboembolic events, bleeding, and mortality in patients treated with 2.5 versus 5 mg twice daily apixaban in both OSs and RCTs. The higher risk profiles of patients in OSs versus RCTs, and higher rates of both bleeding and mortality not attributable to thromboembolism in patients treated with apixaban 2.5 versus 5 mg twice daily suggest that differences in patient characteristics are additional important contributors to the higher than expected thromboembolic event rates in clinical practice.

Apixaban: An Update of the Evidence for Its Place in the Prevention of Stroke in Patients with Atrial Fibrillation.

Oral anticoagulant therapy for stroke prevention in atrial fibrillation patients has been remarkably changed by the introduction of non-vitamin k oral anticoagulants (NOAC). Apixaban was the third NOAC introduced to clinical practice. Aim was to outline the current evidence for Apixaban in stroke prevention in atrial fibrillation patients in the randomized trials and real-world data. Apixaban has been shown to be superior to warfarin in preventing stroke and systemic embolism and causes significantly less major bleeding based on large randomized trials. These data are confirmed in real-world studies. Apixaban has been shown to be safe and effective in atrial fibrillation patients in acute coronary syndrome or undergoing PCI in combination with a P2Y12 inhibitor. Regarding expanded use of apixaban also in valvular heart disease patients, there is still missing knowledge in relation to the safety and efficacy of apixaban which is being addressed by ongoing randomized clinical trials.

Apixaban for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation in France: The PAROS cross-sectional study of routine clinical practice

Non-vitamin K antagonist oral anticoagulants (NOACs), including apixaban, are recommended for prevention of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF). To describe the characteristics of patients starting anticoagulant treatment, identify the characteristics associated with apixaban prescription, and describe apixaban use in France. This was a non-interventional multicentre French study. Patients with NVAF (aged≥18 years) with anticoagulant treatment started in the preceding 3 months were evaluated in four groups (NOAC [apixaban, dabigatran or rivaroxaban] or vitamin K antagonist [VKA]). Data from 2027 patients were eligible for analysis. Mean age was 73.0±11.2 years, 56.6% were men and 80.2% were anticoagulant naïve. Stage≥4 chronic kidney disease was present in 2.2% of patients prescribed apixaban, none of those prescribed dabigatran or rivaroxaban, and 16.8% of those prescribed VKAs. The median CHA2DS2-VASc score was 3 for all three NOACs and 4 for VKAs; the median HAS-BLED score was≥3 for 2.5-5.9% of patients prescribed NOACs and 12.0% of those prescribed VKAs. Apixaban was more likely to be prescribed than other NOACs in older patients with higher bleeding risk and decreased renal function, and VKAs in patients with lower bleeding risk and better renal function. Patients received a reduced dose (5mg/day; 30.4% patients) or a full dose (10mg/day; 69.6% patients) of apixaban. Only 79.3% of patients prescribed apixaban had doses consistent with the summary of product characteristics; underdosing was more frequent than overdosing. Off-label use of apixaban was observed, mainly in elderly patients, despite normal renal function and weight. Initiation of apixaban versus NOACs was more common among patients with increased age, higher bleeding risk and decreased renal function, whereas initiation of apixaban versus VKAs was more common among patients with lower bleeding risk and better renal function.

Cost-Effectiveness of Apixaban For Stroke Prevention In Atrial Fibrillation: An Kazakhstan Perspective

Cost-Effectiveness of Apixaban For Stroke Prevention In Atrial Fibrillation: An Kazakhstan Perspective

Standard and reduced doses of dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation: a nationwide cohort study.

Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF). We compared effectiveness and safety of standard and reduced dose NOAC in AF patients. Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula). Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%). Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban.

2049Standard and reduced doses of dabigatran, rivaroxaban, and apixaban for stroke prevention in atrial fibrillation: a nationwide cohort study

2049Standard and reduced doses of dabigatran, rivaroxaban, and apixaban for stroke prevention in atrial fibrillation: a nationwide cohort study

Adherence to Rivaroxaban, Dabigatran, and Apixaban for Stroke Prevention in Incident, Treatment-Naïve Nonvalvular Atrial Fibrillation

Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used for prevention of stroke secondary to nonvalvular atrial fibrillation (NVAF). Increased use of NOACs is partially a result of simplified regimens compared with warfarin, which has been associated with poor adherence and persistence to therapy. Few studies have assessed adherence to NOACs, especially using contemporary data now that multiple NOACs are available. To evaluate adherence to NOACs in a cohort of newly diagnosed NVAF patients who are commercially insured. Incident, treatment-naïve NVAF patients were identified in 2013 from a large claims database. Patients were included who initiated rivaroxaban, dabigatran, or apixaban within 30 days after diagnosis. Subjects were required to have 12 months of pre-index information to assess demographic and clinical characteristics (comorbidities, CHA2 DS2-VASc, and HAS-BLED scores). Adherence to the index medication and adherence to any oral anticoagulant was assessed using proportion of days covered (PDC) at 3, 6, and 9 months. The number of switches and gaps in therapy were also evaluated. Analyses were stratified by stroke risk scores, and a logistic regression model was used to control for factors that may predict high adherence (PDC ≥ 0.80). A total of 3,455 rivaroxaban, 1,264 dabigatran, and 504 apixaban users were included with no major clinical or demographic differences between groups. At 3, 6, and 9 months of follow-up, dabigatran had lower adherence (PDC = 0.77, 0.67, and 0.62) compared with rivaroxaban (PDC = 0.84, 0.75, and 0.70; P < 0.001) and apixaban (PDC = 0.82, 0.75, and 0.71; P < 0.001), as well as nearly twice the number of switches to either other anticoagulants or antiplatelet therapy. At 9 months, 55.0% of rivaroxaban initiators had PDC ≥ 0.80, which was comparable with 56.8% for apixaban and significantly greater than 46.7% for dabigatran (P < 0.001). Adherence was higher overall as stroke risk increased and showed dabigatran had consistently lower adherence compared with the other NOACs. Overall adherence to any oral anticoagulants, allowing for switches to another NOAC or warfarin, was not dependent on the index medication (9-month PDC = 0.74, 0.71, and 0.74 for rivaroxaban, dabigatran, and apixaban initiators). Adjusted analyses showed that increasing age and comorbid hypertension and diabetes were associated with higher adherence. Compared with rivaroxaban, dabigatran initiators had nearly 30% lower odds of being adherent to their index medication, and no differences were observed between apixaban and rivaroxaban. At 9 months, there were no differences between NOACs for overall adherence to oral anticoagulants. In this real-world analysis of adherence to NOACs, rivaroxaban and apixaban had favorable profiles compared with dabigatran, and rivaroxaban appeared to have higher overall adherence among the NOACs. Clinicians and managed care organizations should consider the implications of lower adherence on clinical outcomes as well as quality assessment. The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant number UL1TR000117. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Brown reports receiving a training fellowship from Human and Pfizer. Study concept and design were contributed by Brown and Shewale. Talbert took the lead in data collection, along with Brown, and data interpretation was primarily performed by Brown, along with Shewale. The manuscript was written primarily by Brown, along with Shewale, and revised by all the authors.

PCV15 - Adherence to Rivaroxaban, Dabigatran, and Apixaban for Stroke Prevention in Incident, Treatment-Naïve Non-Valvular Atrial Fibrillation

PCV15 - Adherence to Rivaroxaban, Dabigatran, and Apixaban for Stroke Prevention in Incident, Treatment-Naïve Non-Valvular Atrial Fibrillation

Economic Evaluation of Warfarin, Dabigatran, Rivaroxaban, and Apixaban for Stroke Prevention in Atrial Fibrillation

BackgroundAtrial fibrillation is a major risk factor for stroke, which causes thousands of deaths and sequelae. It is recommended that atrial fibrillation patients at medium or high risk of stroke use an oral anticoagulant to reduce the risk of stroke. In the past few years, three new oral anticoagulants (NOACs), dabigatran, rivaroxaban, and apixaban, have been introduced in competition to the older oral anticoagulant warfarin.ObjectiveThe objective of this study was to evaluate the relative cost effectiveness of warfarin, dabigatran, rivaroxaban, and apixaban in a Norwegian setting.MethodsWe created a probabilistic decision–analytic Markov model to simulate the life of patients with atrial fibrillation. We performed several scenario analyses, including changing the switching age for dabigatran from 80 to 75 years old.ResultsAssuming the European Society of Cardiology guidance, sequential dabigatran (2 × 150 mg daily until 80 years old, 2 × 110 mg thereafter) seems to be the most cost-effective alternative for high-risk AF patients. For medium-risk patients, apixaban (2 × 5 mg daily) seems to be somewhat more effective than dabigatran, but dabigatran is still marginally the most cost-effective alternative. In scenario analyses reducing dabigatran from 2 × 150 mg to 2 × 110 mg at the age of 75 years (instead of at age 80), apixaban (2 × 5 mg daily) becomes the most cost-effective alternative for both risk groups.ConclusionWe have found apixaban or sequential dabigatran to be the alternatives most likely to be considered cost effective, depending on the switching age for dabigatran. These conclusions are highly sensitive to assumptions made in the analysis.Electronic supplementary materialThe online version of this article (doi:10.1007/s40273-014-0152-z) contains supplementary material, which is available to authorized users.

Efficacy and safety of edoxaban in comparison with dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation

Large Phase 3 clinical trials for stroke prevention in atrial fibrillation (AF) have compared non-vitamin K antagonist oral anticoagulants (NOACs) against warfarin, with the edoxaban trial only recently reported. In the absence of head to head trials directly comparing these NOACs against each other, we compared the efficacy and safety of edoxaban to other agents by an indirect comparison analysis. We performed an indirect comparison analysis of edoxaban (2 dose strategies) against apixaban (1 dose), dabigatran etexilate (2 doses) and rivaroxaban (1 dose), for their relative efficacy and safety against each other. For high-dose edoxaban vs apixaban, there were no significant differences in efficacy endpoints, mortality, myocardial infarction and major bleeding. Apixaban was associated with less major or clinically relevant non-major bleeding (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.70-0.90) and gastrointestinal bleeding (HR 0.72; 95% CI 0.53-0.99). For dabigatran 110 mg twice daily, there were no significant differences in the main efficacy or safety endpoints. Dabigatran 150 mg bid was associated with lower stroke/systemic embolism (SE) (HR 0.75; 95% CI 0.56-0.99), stroke (HR 0.73; 95% CI 0.55-0.96) and haemorrhagic stroke (HR 0.48; 95% CI 0.23-0.99). There were no significant differences between high-dose edoxaban vs rivaroxaban for efficacy endpoints or mortality, but rivaroxaban had more major and/or clinically relevant non-major bleeding. When compared to low-dose edoxaban, apixaban was associated with lower stroke/SE (HR 0.70; 95% CI 0.55-0.89), stroke (HR 0.70; 95% CI 0.55-0.92) and ischaemic stroke (HR 0.65; 95% CI 0.50-0.89), but more major bleeding (HR 1.47; 95% CI 1.20-1.80). For dabigatran 110 mg bid, there were no significant differences in the efficacy endpoints, but dabigatran 110 mg bid had higher major (and gastrointestinal) bleeding. Dabigatran 150 mg bid and rivaroxaban were associated with lower stroke/SE and ischaemic stroke, but higher bleeding rates. In the present analysis, we have provided for the first time, comparisons of efficacy and safety of edoxaban against other NOACs. Notwithstanding the significant limitations of an indirect comparison analysis, some differential effects are evident with the NOACs for stroke prevention, allowing us to allow the prescriber a 'choice' to be able to fit the drug to the patient clinical profile (and vice versa).

Abstract 18820: Bayesian Meta-Analysis of the Novel Oral Anticoagulants versus Warfarin in Patients With Renal Failure

The novel oral anticoagulants (NOACS) dabigatran, rivaroxaban and apixaban for prevention of stroke and systemic embolization in atrial fibrillation are attractive alternatives to warfarin. Controversy exists regarding the use of these medication in renal failure. To compare differential benefit, we performed a Bayesian meta-analysis examining the efficacy and safety of the NOACS versus warfarin in patients with renal failure Methods: Using data from the 3 major trials investigating the novel oral anticoagulants, we conducted a Bayesian meta-analysis of patients stratified by creatinine clearance of 80 ml/min. The primary endpoints of stroke and systemic embolization were assessed, along with safety endpoints of major bleeding, if available. A Bayesian analysis was performed on each group, defining probabilities of benefit for the posterior probability. From this data, sequential Bayesian meta-analysis was performed and posterior probabilities were obtained. Results: Posterior probabilities for stroke and systemic embolization indicate that NOACS in patients with CrCl &gt;80 ml/min have an 74.8% probability of benefit over warfarin. In patients with CrCl 50-80 ml/min there is 95.5% probability of benefit. Patients with CrCl &lt;50 ml/min there is a 93.7% probability of benefit of NOACS over warfarin. Analysis of bleeding events using available data showed a trend towards benefit of NOACS versus warfarin in incidence of major bleeding events. Conclusions: The use of novel oral anticoagulants in patients with renal failure confers a high probability of benefit over warfarin in prevention of stroke and systemic embolization. The NOACS appear to have potentially improved bleeding outcomes in this subgroup, though data is limited. This analysis suggests that the novel oral anticoagulants are more effective and are at least as safe in patients with renal failure when compared with warfarin.

A review of apixaban for stroke prevention in atrial fibrillation: insights from ARISTOTLE

Atrial fibrillation (AF) is associated with significant mortality and morbidity, and stroke represents the most-feared complication. Consequently, AF treatment has focused on thromboprophylaxis, with warfarin as the mainstay of therapy. However, concerns over ease of use and safety have limited its use. Three novel oral anticoagulants have been approved for use in stroke prevention in AF based on randomized data: 1) dabigatran, studied in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY); 2) rivaroxaban, studied in Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF); and 3) apixaban, studied inApixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE). In this review, we focus on apixaban and discuss subgroup analyses that have been performed in the three trials comparing novel oral anticoagulants with warfarin. We conclude with recommendations regarding further investigations.

Potential impact of new oral anticoagulants on the management of atrial fibrillation‐related stroke in primary care

AimAnticoagulant prophylaxis with vitamin K antagonists (such as warfarin) is effective in reducing the risk of stroke in patients with atrial fibrillation (AF). New oral anticoagulants have emerged as potential alternatives to traditional oral agents. The purpose of this review was to summarise the effectiveness and safety of rivaroxaban, dabigatran and apixaban in stroke prevention in patients with AF in phase III trials, evaluate their cost-effectiveness and consider the implications for primary care.MethodologyA literature search was performed between 2007 and 2012, selecting all phase III trials (ROCKET AF, RE-LY and ARISTOTLE) of new oral anticoagulants and relevant cost–benefit studies.ResultsEvidence shows that all three agents are at least as effective as warfarin in the prevention of stroke and systemic emboli, with similar safety profiles. Cost–benefit studies of rivaroxaban and dabigatran further confirm their potential use as alternatives to warfarin in clinical practice. These observations may allow stratification of the general practice AF population, to help prioritise which patients may benefit from receiving a new oral anticoagulant.ConclusionThe clinical and economic benefits of the new oral anticoagulants, along with appropriate risk stratification, may enable a higher number of patients with AF to receive effective and convenient prophylaxis for stroke prevention.

Recent Advances in Antithrombotic Therapy for Stroke Prevention in Patients With Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia and patients with AF have a higher risk for stroke than the general population. The prevalence of AF is increasing, which underscores the importance of understanding the therapeutic options available for stroke prevention in the primary care setting. This article examines evidence for the use of novel oral anticoagulant (OAC) therapy, including the direct thrombin inhibitor dabigatran and the activated factor X inhibitors rivaroxaban and apixaban for stroke prevention in patients with AF. Although warfarin therapy is the gold standard for prevention of stroke, its use is associated with significant challenges related to drug–drug and food–drug interactions. Warfarin use also requires frequent blood monitoring to maintain anticoagulation within a narrow therapeutic window. Overall, the novel OACs are as good as, or better than, warfarin therapy for stroke prevention in patients with AF, and they have a comparable or reduced risk of associated major bleeding. In addition, the novel OACs have fewer drug–drug and food–drug interactions and do not require continuous blood monitoring. Integration of the novel OACs into clinical practice offers patients with AF new treatment options, and as therapeutic use of the novel OACs increases, real-world experience will add to our understanding of the value of these agents.

Abstract 18743: Bayesian Comparative Analysis for Prevention of Stroke and Net Clinical Benefit of Novel Oral Anticoagulants in Non-Valvular Atrial Fibrillation

Background: The recent emergence of novel oral anticoagulants dabigatran, rivaroxaban and apixaban for prevention of stroke and systemic embolization in atrial fibrillation are attractive alternatives to warfarin. Despite this, the differences in efficacy and bleeding events between these medications remains unclear. To compare differential benefit, we performed a Bayesian analysis comparing the efficacy and safety parameters of the 3 novel agents. Methods: Using data from the 3 major trials investigating the novel oral anticoagulants, we conducted a Bayesian analysis using null prior probabilities, which is particularly suited to indirect comparisons. The primary endpoints of stroke and systemic embolization were assessed, along with safety endpoints of major bleeding. A Bayesian analysis was performed on each group, defining probabilities of benefit for the posterior probability. From this data, net clinical benefit calculations were performed and posterior probabilities were obtained. Results: Posterior probabilities for stroke and systemic embolization indicate the apixaban, rivaroxaban and dabigatran have an 87.3%, 88.7%, and 66.3% probability of benefit over warfarin, respectively. Major bleeding events were found to have a 98.6%, 88.0% and 55.0% probability of benefit over warfarin. Net clinical benefit analysis indicates benefit with apixaban and rivaroxaban that was greater than dabigatran. Conclusions: Using Bayesian analytic techniques, all of the novel oral anticoagulants were found to be non-inferior to warfarin. However, the effectiveness in prevention of stroke suggests that both apixaban and rivaroxaban significantly outperform dabigatran. Net clinic benefit and safety endpoints support the use of apixaban as opposed to rivaroxaban and dabigatran. While more data emerges investigating the differential benefit of these new medications, Bayesian techniques offer novel comparative statistics which can guide clinical decision making.