Warfarin In Nonvalvular Atrial Fibrillation Research Articles

NET CLINICAL BENEFIT OF A REDUCED DOSE OF DIRECT ORAL ANTICOAGULANTS IN NON-VALVULAR ATRIAL FIBRILLATION: A META-ANALYSIS OF RANDOMIZED TRIALS

Objective: To evaluate the net clinical benefit of a reduced dose of direct oral anticoagulants (DOACs) compared to warfarin in nonvalvular atrial fibrillation. Design and method: We searched three electronic databases covering the period until end-February 2021. All-cause death, non-fatal stroke/systemic embolism, and major bleeding events, with or without the inclusion of myocardial infarction, were used to define two different net clinical benefit outcomes. In addition, we evaluated different component outcomes of net clinical benefit as secondary outcomes. Finally, each outcome's risk ratios and 95% Confidence Intervals (CI) were calculated (random-effects model). Results: In the four randomized trials included (n = 29,779 patients), the net clinical benefit - with or without the inclusion of myocardial infarction - of low-dose DOACs, compared to warfarin, was a 12% (95% CI, 7%-16%) or a 10% (95% CI, 5%-13%) reduction of events, respectively. Compared to warfarin, the reduced dose of DOACs decreased death outcomes, major bleeding events, and hemorrhagic stroke, whereas all thrombotic outcomes were not different among the groups. Conclusions: DOACs at low doses present a more favorable net clinical benefit profile than warfarin.

Effectiveness and Safety of Rivaroxaban Versus Warfarin among Nonvalvular Atrial Fibrillation Patients with Concomitant Obstructive Sleep Apnea

Background Obstructive sleep apnea (OSA) is associated with an increased incidence of atrial fibrillation (AF), hypertension, diabetes, heart failure, coronary heart disease, stroke, and death. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular AF (NVAF) patients with concomitant OSA. Methods This was an analysis of electronic health record (EHR) data from November 2010 to December 2021. We included adults with NVAF and OSA at baseline, newly initiated on rivaroxaban or warfarin, and with ≥12 months of prior EHR activity. Patients with valvular disease, alternative indications for oral anticoagulation, or who were pregnant were excluded. The incidence rates of developing stroke or systemic embolism (SSE) and bleeding-related hospitalization were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using propensity score-overlap weighted proportional hazards regression. Multiple sensitivity and subgroup analyses were performed. Results We included 21,940 rivaroxaban (20.1% at the 15 mg dose) and 38,213 warfarin (time-in-therapeutic range = 47.3 ± 28.3%) patients. Rivaroxaban was found to have similar hazard of SSE compared to warfarin (HR = 0.92, 95% CI = 0.82-1.03). Rivaroxaban was associated with a reduced rate of bleeding-related hospitalizations (HR = 0.85, 95% CI = 0.78-0.92) versus warfarin, as well as reductions in intracranial (HR = 0.76, 95% CI = 0.62-0.94) and extracranial (HR = 0.89, 95%CI = 0.81-0.97) bleeding. Upon sensitivity analysis restricting the population to men with a CHA 2 DS 2 VASc score ≥2 or women with a score ≥3, rivaroxaban was associated with a significant 33% risk reduction in SSE and 43% reduction in the risk of bleeding-related hospitalization. No significant interaction for the SSE or bleeding-related hospitalization outcomes was observed upon subgroup analyses. Conclusion Among patients with NVAF and OSA, rivaroxaban had similar SSE risk versus warfarin but was associated with reductions in any intracranial and extracranial bleeding-related hospitalizations. Rivaroxaban was associated with significant reductions in SSE and bleeding-related hospitalizations when the study population was restricted to patients with a moderate-to-high risk of SSE. These data should provide prescribers with additional confidence in selecting rivaroxaban in NVAF patients who have OSA at the time of anticoagulation initiation.

Effectiveness and safety of oral anticoagulants in non-valvular atrial fibrillation patients with prior bleeding events: a retrospective analysis of administrative claims databases

IntroductionThere are a paucity of real-world data examining effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in nonvalvular atrial fibrillation (NVAF) patients with prior bleeding.MethodsThis retrospective analysis included data from 5 insurance claims databases and included NVAF patients prescribed OACs with prior bleeding. One-to-one propensity score matching was conducted between NOACs and warfarin and between NOACs in each database. Cox proportional hazards models were used to evaluate the risk of stroke/systemic embolism (SE) and MB.ResultsA total of 244,563 patients (mean age 77; 50% female) with prior bleeding included 55,094 (22.5%) treated with apixaban, 12,500 (5.1%) with dabigatran, 38,246 (15.6%) with rivaroxaban, and 138,723 (56.7%) with warfarin. Apixaban (hazard ratio [HR]: 0.76 [95% CI: 0.70, 0.83]) and rivaroxaban (HR: 0.79 [95% CI: 0.71, 0.87]) had a lower risk of stroke/SE vs. warfarin. Apixaban (HR: 0.67 [95% CI: 0.64, 0.70]) and dabigatran (HR: 0.88 [95% CI: 0.81, 0.96]) had a lower risk of MB vs. warfarin. Apixaban patients had a lower risk of stroke/SE vs. dabigatran (HR: 0.70 [95% CI: 0.57, 0.86]) and rivaroxaban (HR: 0.85 [95% CI: 0.76, 0.96]) and a lower risk of MB than dabigatran (HR: 0.73 [95% CI: 0.67, 0.81]) and rivaroxaban (HR: 0.64 [95% CI: 0.61, 0.68]).ConclusionsIn this real-world analysis of a large sample of NVAF patients with prior bleeding, NOACs were associated with similar or lower risk of stroke/SE and MB vs. warfarin and variable risk of stroke/SE and MB against each other.

Direct oral anticoagulants vs warfarin in non-valvular atrial fibrillation. Meta-analysis, includes all published trials

Abstract Introduction Warfarin, despite its limitations, is still used as standard treatment in patients with Atrial Fibrillation, but it has been demonstrated that Direct Oral Anticoagulants (DOAC) offer many advantages over warfarin in the prevention of strokes. Purpose The goal was to determinate the safety and effectiveness in reducing systemic thromboembolism, ischemic stroke, hemorrhagic stroke, cerebral hemorrhage and cardiovascular mortalityof the direct oral anticoagulants (DOACs) over warfarin in patients with non-valvular atrial fibrillation, conducting an analysis of the studies of DOACs, including the ENGAGE study on the use of edoxaban, affirming its safety including the pivotal essays available. Method A systematic search of PubMed's bibliographic database was made for the selection of the articles.Clinical essays from less than 10 years, in phase III and multicentric studies were selected. Results The main objective was the significant reduction in the incidence of stroke/systemic thromboembolism with the use of DOACs vs. Warfarin (2,73% vs. 3,24%), the reduction of hemorrhagic stroke was (0.41% vs. 0.94%), ischemic stroke (3.12% vs. 3.5%), cardiovascular death with DOACs was 6.02% vs. Warfarin 6.84%, (compared with previous studies that demonstrated effectiveness with max doses affirming safety and effectiveness). Conclusion Our meta-analysis is the first to date to evaluate all the pivotal trials published,we include the ENGAGE trial. In non-valvular atrial fibrillation, the use of DOACs, in comparison with Warfarin, significantly reduced the risk of stroke/systemic thromboembolism by 16.3%, ischemic stroke by 11.1%, hemorrhagic stroke by 54.6%, cardiovascular mortality by 12.9%. Funding Acknowledgement Type of funding sources: None.

Anticoagulation Control with Acenocoumarol or Warfarin in Non-Valvular Atrial Fibrillation in Primary Care (Fantas-TIC Study).

Introduction: The use of vitamin K antagonists (VKAs) in non-valvular atrial fibrillation (NVAF) is complicated due to the narrow therapeutic margin they present and their unpredictable dose–response relationship. Most studies are based on warfarin, with the results being extrapolated to acenocoumarol. However, studies comparing the two treatments in terms of the degree of anticoagulation control are scarce, justifying the present study. Main factors associated with poor control of time in therapeutic range (TTR) of anticoagulated patients are also studied. Methods: Cross-sectional study, with real-world data from patients treated in primary care (PC). Data were obtained from the System for the Improvement of Research in PC (SIDIAP) database, covering 60,978 NVAF-anticoagulated patients from 287 PC centres in 2018. Descriptive statistics were derived, and odds ratios were estimated by multivariate logistic regression. Results: 41,430 patients were considered: 93% were being treated with acenocoumarol and 7% with warfarin. There was no difference in poor control of TTR between the two types of VKA treatment, acenocoumarol and warfarin (38.9 vs. 38.4; p = 0.610). Poor anticoagulation control was mainly associated with advanced alcoholism (OR = 1.38), liver failure (OR = 1.37) and intracranial haemorrhage (OR = 1.35) as well as female sex, age < 60 years, cardiovascular history, diabetes mellitus and other variables. Conclusions: There is no association between poor anticoagulation control and the type of VKA treatment administered. Factors associated with poor control of TTR must be considered in clinical practice to improve control and decision-making.

DIRECT ORAL ANTICOAGULANTS VS. WARFARIN FOR NEW ONSET POST-CARDIAC SURGERY NON-VALVULAR ATRIAL FIBRILLATION

Randomized clinical trials of direct oral anticoagulants (DOAC) vs. warfarin in non-valvular atrial fibrillation (NVAF) excluded individuals with post-cardiac surgery atrial fibrillation. We sought to compare short-term outcomes with DOACs vs. warfarin for new onset post-cardiac surgery NVAF.

P3470Comparative effectiveness and safety of non-vitamin K oral anticoagulants and warfarin in non-valvular atrial fibrillation - a cohort study in 3 Nordic countries

Abstract Background Non-vitamin K oral anticoagulants (NOACs) are an alternative to warfarin in the prevention of stroke in non-valvular atrial fibrillation (NVAF). Nordic countries have high quality of warfarin treatment, making them an especially suitable setting for assessing effectiveness and safety of NOACs against warfarin. Purpose The BEYOND Pooled (BEnefit of NOACs studY of nOn-valvular AF patieNts in NorDic countries) study compared risks of ischaemic or haemorrhagic stroke/systemic embolism (S/SE), and risk of bleeding with acute hospitalisation with an overnight stay (bleeding) in NVAF patients treated with apixaban, dabigatran or rivaroxaban, each compared with warfarin treatment. Methods A cohort study of treatment-naïve adult NVAF patients dispensed apixaban, dabigatran, rivaroxaban or warfarin was identified from 01 Jan 2013 to 31 Dec 2016. The population and study variables were identified from national registries in Denmark, Norway and Sweden. After 1:1 propensity score (PS) matching for each NOAC-warfarin comparison, individual-level data were pooled across the countries. Cox proportional-hazards regression was used to estimate adjusted hazard ratios (aHRs) of the endpoints. Results PS matched NOAC cohort sizes were: apixaban (55,696) dabigatran (28,526) and rivaroxaban (30,701), and the total follow-up in the PS-matched population was 291,171 years (mean 1.3 years). During the follow-up, 35,450 oral anticoagulation (OAC) patients had a S/SE and 38,620 OAC patients had bleeding. Adjusted HRs for the two endpoints are presented in the table. PH assumption has not been formally tested but cum incidence curves did not indicate substantial differences in the effects over time. Table 1. Adjusted hazard ratios (aHR) of stroke/systemic embolism and bleeding for non-vitamin K oral anticoagulants versus warfarin Endpoint Apixaban vs Warfarin: aHR (95% CI) Dabigatran vs Warfarin: aHR (95% CI) Rivaroxaban vs Warfarin: aHR (95% CI) Stroke/SE 0.93 (0.85–1.03) 0.89 (0.80–1.00) 0.97 (0.88–1.08) Bleeding 0.72 (0.67–0.77) 0.87 (0.80–0.95) 1.12 (1.04–1.20) Conclusions Relative to warfarin, apixaban and dabigatran were associated with lower rates of bleeding whereas rivaroxaban was associated with a higher rate. The three NOACs had comparable rates of stroke and systemic embolism relative to warfarin. Acknowledgement/Funding This study was funded by the Pfizer/Bristol-Myers Squibb Alliance.

Re-evaluating Safety and Effectiveness of Dabigatran Versus Warfarin in a Nationwide Data Environment: A Prevalent New-User Design Study.

IntroductionThe new user cohort design is widely used to assess the effects of a new drug, such as dabigatran, but inherently excludes some users due to prior use of the comparator drug, for example warfarin. The prevalent new-user design offers a solution that includes all eligible users of the new drug.ObjectiveTo evaluate the safety and effectiveness of dabigatran versus warfarin in non-valvular atrial fibrillation (NVAF) patients with prevalent new-user design.MethodsTaiwan National Health Insurance and mortality data from 2011 through 2015 were utilized. From an incident NVAF cohort, we identified dabigatran initiators as either incident or prevalent (switchers from warfarin) new users. Time- and prescription-based exposure sets were formed for dabigatran initiators to account for prior warfarin prescriptions. A comparable warfarin user was matched on the time-conditional propensity score to the dabigatran initiator in each set. The matched patients were followed for clinical outcomes, with Cox proportional hazards model used to estimate hazard ratios (HRs).ResultsThere were 10,811 dabigatran initiators, including 22% prevalent new users (switchers), who formed the exposure sets and were matched 1:1 to warfarin users. Dabigatran use was associated with lower risks of intracranial hemorrhage (HR 0.51; 95% confidence interval [CI] 0.39, 0.66) and gastrointestinal bleeding (HR 0.81; 95% CI 0.70, 0.92), compared with warfarin use. These effects were similar between the incident and prevalent new users.ConclusionUsing a design that includes both incident and prevalent new users of dabigatran, the use of dabigatran is associated with lower major bleeding risk than warfarin use among patients with incident NVAF.Electronic supplementary materialThe online version of this article (10.1007/s40801-019-0156-2) contains supplementary material, which is available to authorized users.

PO357 Effectiveness and Safety of Dabigatran Versus Warfarin in Non-Valvular Atrial Fibrillation: A Serbian Cohort Study

We sought to compare VeraCept (VC175), a novel nitinol intrauterine contraceptive (IUC) with 175 square-mm of copper surface area, to a copper T380S IUC.We enrolled parous women into a randomized subject-blinded comparison of VC175 and a copper T380S in a 2:1 fashion at a single clinic. The primary outcomes were total adverse events and continuation at 12 months. We also examined pain on insertion, ease of placement, expulsion, tolerability and pregnancy. Subjective ratings were on a 5-point Likert scale (0, no pain to 5, worst pain). We followed subjects through 24-month follow-up.We enrolled 300 women with 199 randomized to VC175 and 101 to the T380S. Insertion was successful in 198 subjects for VC175 and 100 for the T380S. Mean age was 25 years (range 18, 41), and median parity was 2 (range 1, 8), with 39% having only had Cesarean deliveries. No subjects developed clinical infection or reported serious adverse events. In the VC175 and T380S groups, mean pain at insertion was 1.4 and 2.4, respectively (p<.01). At the 12-month primary endpoint for VC175 and T380S, respectively, continuation was 84% and 68% (p<.002) with expulsions in 5.0% and 12.0% (p<.05) and removal for pain/bleeding in 3.5% and 17.0% (p<.01). At the 24-month visit for VC175 and T380S, respectively, continuation was 77% and 62% (p<.02 by log-rank). One ectopic pregnancy was identified at the 12-month follow-up in a VC175 user. No other pregnancies were diagnosed. With 297.3 and 132.4 woman-years, pregnancy rates were 0.3 and 0.0 per 100 woman-years for VC175 and T380S, respectively.VC175 resulted in less pain at insertion, fewer expulsions and higher total continuation than the T380S, with similar contraceptive efficacy.VC175 is a promising new intrauterine copper contraceptive on a nitinol frame that warrants further clinical trials.

Periprocedural Outcomes of Direct Oral Anticoagulants Versus Warfarin in Nonvalvular Atrial Fibrillation.

Direct oral anticoagulants (DOACs) are surpassing warfarin as the anticoagulant of choice for stroke prevention in nonvalvular atrial fibrillation. DOAC outcomes in elective periprocedural settings have not been well elucidated and remain a source of concern for clinicians. The aim of this meta-analysis was to evaluate the periprocedural safety and efficacy of DOACs versus warfarin in patients with nonvalvular atrial fibrillation. We reviewed the literature for data from phase III randomized controlled trials comparing DOACs with warfarin in the periprocedural period among patients with nonvalvular atrial fibrillation. Substudies from 4 trials (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation], and ENGAGE-AF [Effective Anticoagulation With Factor xA Next Generation in Atrial Fibrillation]) were included in the meta-analysis. DOACs as a group and warfarin were compared in terms of the 30-day pooled risk for stroke/systemic embolism, major bleeding, and death, according to whether the study drug was interrupted or not periprocedurally. The overall relative risk (RR) was estimated with a random-effects model. The I2 test was used to assess heterogeneity in RR among the studies. In the uninterrupted anticoagulant strategy, there were no differences in the rates of stroke/systemic embolism (pooled risk, 0.6% [29 events/4519 procedures] versus 1.1% [31/2971]; RR, 0.70; 95% confidence interval [CI], 0.41-1.18) and death (1.4% versus 1.8%; RR, 0.77; 95% CI, 0.53-1.12) between DOACs and warfarin and significantly fewer major bleeding events (2.0% versus 3.3%; RR, 0.62; 95% CI, 0.47-0.82) with DOACs compared to warfarin. Under an interrupted strategy, there was no significant difference between DOACs versus warfarin for stroke/systemic embolism (0.4% [41/9260] versus 0.5% [31/7168]; RR, 0.95; 95% CI, 0.59-1.55), major bleeding (2.1% versus 2.0%; RR, 1.05; 95% CI, 0.85-1.30), and death (0.7% versus 0.6%; RR, 1.24; 95% CI, 0.76-2.04). The studies were homogeneous ( I2=0.0%) for all calculated pooled associations except for the RR of death in the interrupted strategy ( I2=26.3%). The short-term safety and efficacy of DOACs and warfarin are not different in patients with nonvalvular atrial fibrillation periprocedurally. Under an uninterrupted anticoagulation strategy, DOACs are associated with a 38% lower risk of major bleeding compared with warfarin.

Oral anticoagulants and atrial fibrillation: A South African perspective.

This review evaluates the current literature on available oral anticoagulants and atrial fibrillation with specific relevance to the South African (SA) public healthcare sector, focusing on the pharmacology and monitoring of anticoagulants, current guidelines, initiation of treatment and risk stratification, effectiveness of treatment, cost-effectiveness and specific costing implications. The direct-acting oral anticoagulants (DOACs) are superior to warfarin, with dabigatran being the preferred treatment option in patients with non-valvular atrial fibrillation (NVAF). Warfarin is still the preferred anticoagulant in patients with renal failure and prosthetic heart valves and is still the most cost-effective anticoagulant in the SA public sector setting. There is a growing body of evidence that demonstrates the advantages of DOACs over warfarin in NVAF. Warfarin will remain the anticoagulant of choice until cheaper generic DOACs become available.

Non-vitamin K oral anticoagulants are non-inferior for stroke prevention but cause fewer major bleedings than well-managed warfarin: A retrospective register study.

BackgroundFor patients with atrial fibrillation, non-vitamin K oral anticoagulants, or NOACs (dabigatran, rivaroxaban, edoxaban, and apixaban) have been proven non-inferior or superior to warfarin in preventing stroke and systemic embolism, and in risk of haemorrhage. In the pivotal NOAC studies, quality of warfarin treatment was poor with mean time in therapeutic range (TTR) 55–65%, compared with ≥70% in Swedish clinical practice.MethodsWe compared NOACs (as a group) to warfarin in non-valvular atrial fibrillation, studying all 12,694 patients starting NOAC treatment within the Swedish clinical register and dosing system Auricula, from July 1, 2011 to December 31, 2014, and matching them to 36,317 patients starting warfarin using propensity scoring. Endpoints were thromboembolic events and major bleedings that were fatal or required hospital care. Outcome data were collected from validated Swedish hospital administrative and clinical registers.ResultsMean age was 72.2 vs 72.3 years, proportion of males 58.2% vs 57.0%, and mean follow-up time 299 vs 283 days for NOACs and warfarin. Distribution of NOACs was: dabigatran 40.3%, rivaroxaban 31.2%, and apixaban 28.5%. Mean TTR was 70%. There were no significant differences in rates of thromboembolic/thrombotic events or gastrointestinal bleeding. NOAC treated patients had lower rates of major bleeding overall, hazard ratio 0.78 (95% confidence interval 0.67–0.92), intracranial bleeding 0.59 (0.40–0.87), haemorrhagic stroke 0.49 (0.28–0.86), and other major bleeding 0.71 (0.57–0.89).ConclusionFor patients with atrial fibrillation, NOACs are as effective for stroke prevention as well-managed warfarin but cause fewer major bleedings.

Factors driving the use of warfarin and non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

In the past, warfarin was the drug of choice for stroke prevention in patients with atrial fibrillation (AF). Recently, non-vitamin K antagonist oral anticoagulants (NOACs) have been approved as an alternative to warfarin in nonvalvular AF. However, there is a limited amount of real-world data on how NOACs are currently being used in Taiwan. This study was conducted to investigate the factors driving the initiation of anticoagulants and the selection of different anticoagulants in patients with AF. We used National Taiwan University Hospital's electronic database to identify all nonvalvular AF patients from January 1, 2007 to December 31, 2013. Multivariate logistic regression models were used to examine the factors driving the initiation of anticoagulants and the selection of different anticoagulants. Among AF patients, 66.4% of anticoagulants users used NOACs instead of warfarin after the era of NOACs. Patients with female sex, hypertension, ischemic heart disease, cancer, hepatic disease, renal disease, bleeding history, and aspirin use were less likely to be anticoagulant users but are more likely to be anticoagulant users with a history of stroke (odds ratio=2.64; 95% confidence interval, 2.02-3.45). Older age, ischemic heart disease, and aspirin use were the factors associated with NOACs usage, whereas hepatic disease showed the opposite results (odds ratio=0.09; 95% confidence interval, 0.02-0.42). Stroke history was associated with anticoagulant use, whereas comorbidities associated with increased risk of bleeding showed the opposite result. Patients with hepatic disease were less likely to use NOACs.

Efficacy and Safety of Edoxaban in Nonvalvular Atrial Fibrillation: A Meta-analysis of Randomized Controlled Trials

Edoxaban is a potential alternative to warfarin for preventing thromboembolism in atrial fibrillation. However, the efficacy and safety, and the optimal regimen of edoxaban are still controversial. This study compared the efficacy and safety of edoxaban and warfarin in nonvalvular atrial fibrillation, and the effects of different edoxaban dosages. A systematic search for randomized controlled trials comparing edoxaban with warfarin in nonvalvular atrial fibrillation was conducted using PubMed, EMBASE, and the Cochrane Library databases. The main measures and outcomes included efficacy end points (thromboembolic events and all-cause mortality) and safety end points (all bleeding events, major bleeding events, clinically relevant nonmajor bleeding, and minor bleeding). Four studies including 23,001 patients were included in the meta-analysis. Edoxaban was noninferior to warfarin for preventing stroke and systemic embolism (risk ratio [RR] = 1.00; 95% confidence interval [CI], .88-1.13; Z = .01; P = .99). In safety analyses, edoxaban was superior to warfarin in terms of major bleeding, clinically relevant nonmajor bleeding, and minor bleeding (all P <.00001). In terms of optimal dosing, 30 mg/day edoxaban had a significantly lower risk of all bleeding (RR = .79; 95% CI, .75-.83; Z = 9.07; P <.00001) than 60 mg/day, but was inferior at preventing stroke and systemic embolism (RR = 1.31; 95% CI, 1.13-1.51; Z = 3.56; P = .0004). Edoxaban was noninferior to warfarin in terms of efficacy and superior to warfarin in terms of safety. The benefits of edoxaban were related to the dose; efficacy was better at 60 mg/day, but there was lower risk of bleeding at 30 mg/day.

Estimation of the cost-effectiveness of apixaban versus vitamin K antagonists in the management of atrial fibrillation in Argentina.

Apixaban, a novel oral anticoagulant which has been approved for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation, reduces both ischemic and haemorrhagic stroke and produces fewer bleedings than vitamin K antagonist warfarin. These clinical results lead to a decrease in health care resource utilization and, therefore, have a positive impact on health economics of atrial fibrillation. The cost-effectiveness of apixaban has been assessed in a variety of clinical settings and countries. However, data from emergent markets, as is the case of Argentina, are still scarce.We performed a cost-effectiveness analysis of apixaban versus warfarin in non-valvular atrial fibrillation (NVAF) in patients suitable for oral anticoagulation in Argentina. A Markov-based model including both costs and effects were used to simulate a cohort of patients with NVAF. Local epidemiological, resource utilization and cost data were used and all inputs were validated by a Delphi Panel of local experts. We adopted the payer’s perspective with costs expressed in 2012 US Dollars.The study revealed that apixaban is cost-effective compared with warfarin using a willingness to pay threshold ranging from 1 to 3 per capita Gross Domestic Product (11558 – 34664 USD) with an incremental cost-effectiveness ratio of 786.08 USD per QALY gained. The benefit is primarily a result of the reduction in stroke and bleeding events.The study demonstrates that apixaban is a cost-effective alternative to warfarin in Argentina.

OC-026 Novel oral anticoagulants and gastrointestinal bleeding in the real world setting: incidence, endoscopic findings, intervention and use of blood products

<h3>Introduction</h3> Rivaroxaban, apixaban and dabigatran compile the novel oral anticoagulants (NOAC). Since 2012, NOACs are used as first line treatment for atrial fibrillation, pulmonary embolism and deep venous thrombosis at Russells Hall Hospital (RHH). The trial data regarding the risk of gastrointestinal (GI) bleeding has been conflicting, although a meta-analysis found an increased risk of GI bleeding with NOACs as opposed to warfarin (2.3% vs. 1.3%).¹However, little is known about its incidence in the real world setting. We aimed to demonstrate the incidence of GI bleeding, endoscopic findings, time of onset of bleeding and the need for intervention in patients taking NOACs. <h3>Method</h3> We performed a retrospective review of all patients at RHH who received NOACs. These patients were identified from the anticoagulation database and cross-referenced with the GI database and patient notes. Basic demographic, clinical and laboratory data and endoscopic findings were collated. <h3>Results</h3> A total of 2487 patients were identified to be on NOACs of which 61 were found to have an episode of GI bleeding, giving an incidence rate of 2.45%. 54 of 2334 patients were on rivaroxaban, 3 of 77 on apixaban and 4 of 76 on dabigatran with an incidence of GI bleeding of 2.3%, 3.9% and 5.3% respectively. There was a greater incidence found with females than males (55% vs. 45%) with the median age 80 years (range 53–95). The 30-day mortality rate was 11.5% (n = 11). The cause of death were not directly due to GI bleeding. Of these 61 patients, 30 (49.2%) had an upper GI bleed (UGIB) and 31 (50.8%) had a lower GI bleed (LGIB). The median time from starting NOAC to having a GI bleed was 6.7 months (range 2 days-19.7 months). Endoscopy results were varied with the most common findings being haemorrhoids (15.7%), diverticular disease (14.6%), normal findings (12.4%), gastritis (7.9%) and peptic ulcer disease (7.9%). 7 patients (11.5%) required endoscopic intervention and 21 patients (34.4%) required the use of blood products. Although 12.9% of patients with LGIB required endoscopic intervention versus 10% of UGIB, patients with UGIB were more likely to be inpatients (97% vs. 35%), with a greater drop in haemoglobin (median Hb: 87 g/L versus 105 g/L) and the increased use of blood products (53% vs. 16%). <h3>Conclusion</h3> The risk of GI bleeding with NOACs is greater than warfarin, with rivaroxaban being the safest of the three drugs in our cohort and is similar to the published data. Further studies are required to confirm these findings. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Capodanno D, Capranzano P, Giacchi G, Calvi V, Tamburino C. Novel oral anticoagulants versus warfarin in non-valvular atrial fibrillation: a meta-analysis of 50,578 patients. Int J Cardiol. 2013;167(4):1237–41

Outcomes of Temporary Interruption of Rivaroxaban Compared With Warfarin in Patients With Nonvalvular Atrial Fibrillation

Background— During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. Methods and Results— In the 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), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non–central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3–30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36–1.50]; P =0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80–2.00]; P =0.32). Conclusions— TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00403767.

Real-world comparative effectiveness and safety of rivaroxaban and warfarin in nonvalvular atrial fibrillation patients

Background:Rivaroxaban was shown to be effective in reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) in a randomized controlled trial setting.Objective:To assess real-world safety, effectiveness, and persistence associated with rivaroxaban and warfarin in nonvalvular AF patients.Methods:Healthcare claims from Symphony Health Solutions’ Patient Transactional Datasets from May 2011 to July 2012 were analyzed. Adult patients newly initiated on rivaroxaban or warfarin, with ≥2 AF diagnoses (ICD-9-CM: 427.31) and a CHADS2 score ≥1 during the 180 day baseline period were included. Cohorts were matched 1:4 using propensity score methods. Study outcomes were major bleeding, intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, composite stroke and systemic embolism, and venous thromboembolism (VTE) events. Cox proportional hazard models were used to compare event and persistence rates.Results:The matched sample included 3654 rivaroxaban and 14,616 warfarin patients. Matching was adequate, with all standardized differences in patient characteristics <10%. No significant differences were observed for bleeding and composite stroke and systemic embolism outcomes, although rivaroxaban users were associated with significantly fewer VTE events (hazard ratio [HR] = 0.36, 95% confidence interval [CI]: 0.24–0.54, p < 0.0001) compared to warfarin users. Rivaroxaban was also associated with a significantly lower risk of treatment non-persistence (HR = 0.66; 95% CI: 0.60–0.72, p < 0.0001).Limitations:Claims data may have contained inaccuracies, and mortality and laboratory data were not available. Confounding may still have been possible even after propensity score matching. Early use pattern of medications may have changed over time.Conclusion:This analysis suggests that rivaroxaban and warfarin do not differ significantly in real-world rates of composite stroke and systemic embolism and major, intracranial, or GI bleeding. Rivaroxaban, however, was associated with significantly fewer VTE events and significantly better treatment persistence compared with warfarin.

LOW APTT AND BMI PREDICTS THE OCCURRENCE OF ISCHEMIC STROKE IN PATIENTS WITH ATRIAL FIBRILLATION RECEIVING DABIGATRAN

Dabigatran etexilate, oral direct inhibitors of thrombin, was demonstrated to be as efficacious and safe as warfarin in non-valvular atrial fibrillation (AF). However, it remains to be elucidated the usefulness of coagulation test to determine the proper dose of dabigatran to prevent cardiogenic

Dabigatran, Rivaroxaban, or Apixaban versus Warfarin in Patients with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Subgroups

Background. New oral anticoagulants (NOAC; rivaroxaban, dabigatran, apixaban) have become available as an alternative to warfarin anticoagulation in non-valvular atrial fibrillation (NVAF). Methods. MEDLINE and CENTRAL, regulatory agencies websites, clinical trials registers and conference proceedings were searched to identify randomised controlled trials of NOAC versus warfarin in NVAF. Two investigators reviewed all studies and extracted data on patient and study characteristics along with cardiovascular outcomes. Relative risks (RR) and 95% confidence intervals (CI) were estimated using a random effect meta-analysis. Results. Three clinical trials in 50,578 patients were included. The risk of non-hemorrhagic stroke and systemic embolic events (SEE) was similar with the NOAC and warfarin (RR = 0.93; 95% CI = 0.83–1.04), while the risk of intracranial bleeding (ICB) with the NOAC was lower than with warfarin (RR = 0.46; 95% CI = 0.33–0.65). We found differences in the effect size on all strokes and SEE depending on geographic region as well as on non-hemorrhagic stroke, SEE, bleeding and mortality depending on time in therapeutic range. Conclusion. The NOAC seem no more effective than warfarin for prevention of nonhemorrhagic stroke and SEE in the overall NVAF population, but are generally associated with a lower risk of ICB than warfarin.