Effectiveness Of Dabigatran Research Articles

Comparative Treatment Cost, Effectiveness and Safety of Dabigatran, Rivaroxaban and Warfarin in Atrial Fibrillation (AF) Patients: A Descriptive Study from Penang General Hospital (PGH)

Comparative Treatment Cost, Effectiveness and Safety of Dabigatran, Rivaroxaban and Warfarin in Atrial Fibrillation (AF) Patients: A Descriptive Study from Penang General Hospital (PGH)

Comparative effectiveness of rivaroxaban versus warfarin or dabigatran for the treatment of patients with non-valvular atrial fibrillation

BackgroundRivaroxaban is an oral anticoagulant approved in the US for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). We determined the effectiveness and associated risks of rivaroxaban versus other oral anticoagulants in a large real-world population.MethodsWe selected NVAF patients initiating oral anticoagulant use in 2010–2014 enrolled in MarketScan databases. Rivaroxaban users were matched with warfarin and dabigatran users by age, sex, enrolment date, anticoagulant initiation date, and high-dimensional propensity score. Study endpoints, including ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding, were identified from inpatient diagnostic codes. Multivariable Cox models were used to assess associations between type of anticoagulant and outcomes.ResultsThe analysis included 44,340 rivaroxaban users matched to 89,400 warfarin and 16,957 dabigatran users (38% female, mean age 70) with 12 months of mean follow-up. Anticoagulant-naïve rivaroxaban initiators, but not those switching from warfarin, had lower risk of ischemic stroke [hazard ratio (HR) (95% confidence interval (CI)): 0.75 (0.62, 0.91)] and ICB [HR (95%CI): 0.55, (0.39, 0.78)] than warfarin users. In contrast, anticoagulant-experienced rivaroxaban initiators had higher risk of GI bleeding than warfarin users [HR (95%CI): 1.55 (1.32, 1.83)]. Endpoint rates were similar when comparing anticoagulant-naïve rivaroxaban and dabigatran initiators, with the exception of higher GI bleeding risk in rivaroxaban users [HR (95%CI) 1.28 (1.06, 1.54)]. There were no significant differences in the risk of MI among the comparison groups.ConclusionIn this large real-world sample of NVAF patients, effectiveness and risks of rivaroxaban versus warfarin differed by prior anticoagulant status, while effectiveness of rivaroxaban versus dabigatran differed in GI bleeding risk.

Two-year follow-up of patients treated with dabigatran for stroke prevention in atrial fibrillation: Global Registry on Long-Term Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry

GLORIA-AF is a large, global, prospective registry program of newly diagnosed atrial fibrillation (AF) patients with ≥1 stroke risk factors. We describe the effectiveness and safety of dabigatran etexilate over 2 years from routine clinical practice in nearly 3000 patients from GLORIA-AF who are newly diagnosed with non-valvular AF and at risk of stroke. Consecutive enrollment into phase II of GLORIA-AF was initiated following approval of dabigatran for stroke prevention in non-valvular AF. Within this Phase II, 2937 dabigatran patients completed 2-year follow-up by May 2016 and were eligible for analysis. Patients who took at least 1 dose of dabigatran (n=2932) were used to estimate incidence rates. Overall incidence rates per 100 person-years of 0.63 (95% confidence interval [CI], 0.42-0.92) for stroke, 1.12 (0.83-1.49) for major bleeding, 0.47 (0.29-0.72) for myocardial infarction, and 2.69 (2.22-3.23) for all-cause death were observed. For patients taking 150 mg dabigatran twice daily (BID), corresponding rates (95% CI) were 0.56 (0.30-0.94), 1.00 (0.64-1.47), 0.48 (0.25-0.83), and 2.07 (1.55-2.72), respectively. For patients taking 110 mg dabigatran BID, event rates (95% CI) were 0.67 (0.33-1.20), 1.16 (0.70-1.80), 0.43 (0.17-0.88), and 3.16 (2.36-4.15). These global data confirm the sustained safety and effectiveness of dabigatran over 2 years of follow-up, consistent with the results from clinical trials as well as contemporary real-world studies. • Non-vitamin K antagonist (VKA) anticoagulants (NOACs) are the preferred therapy for prevention of ischemic stroke based on phase 3 trials, but there is insufficient information on their efficacy and safety in daily practice, based on prospectively collected data. • This study shows that in non-valvular AF patient population, with up to 2 years of follow-up, the use of dabigatran led to a low incidence of ischemic stroke, major bleeding, and myocardial infarction in routine clinical care, confirming the sustained safety and effectiveness of dabigatran in clinical practice over 2 years of follow-up.

Comparison of the Effectiveness and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Newly Diagnosed Atrial Fibrillation

No studies have performed direct pairwise comparisons of the effectiveness and safety of warfarin and the new oral anticoagulants (NOACs) apixaban, dabigatran, and rivaroxaban. Using 2013 to 2014 claims from a 5% random sample of Medicare beneficiaries, we identified patients newly diagnosed with atrial fibrillation who initiated apixaban, dabigatran, rivaroxaban, warfarin, or no oral anticoagulation therapy in 2013 to 2014. Outcomes included the composite of ischemic stroke, systemic embolism (SE) and death, any bleeding event, gastrointestinal bleeding, intracranial bleeding, and treatment persistence. We constructed Cox proportional hazard models to compare outcomes between each pair of treatment groups. The composite risk of ischemic stroke, SE, and death was lower for NOACs than for warfarin: hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.76 to 0.98 for apixaban; 0.73, 95% CI 0.63 to 0.86 for dabigatran; and 0.82, 95% CI 0.75 to 0.89 for rivaroxaban, all compared with warfarin. There were no differences in effectiveness across NOACs. The risk of any bleeding was lower with apixaban than with warfarin, but higher with rivaroxaban than with warfarin. Apixaban (HR 0.69, 95% CI 0.60 to 0.79) and dabigatran (HR 0.79, 95% CI 0.69 to 0.92) were associated with lower bleeding risk than rivaroxaban. Treatment persistence was highest for apixaban (82%), and lowest for dabigatran and warfarin (64%) (p value <0.001). Compared with warfarin, NOACs are more effective in preventing stroke but their risk of bleeding varies, with rivaroxaban having higher risk than warfarin. Altogether, apixaban had the most favorable effectiveness, safety, and persistence profile.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

What Influences the Cost Effectiveness of Dabigatran versus Warfarin for Stroke Prevention in Atrial Fibrillation: A Systematic Review.

The introduction of new oral anticoagulants for the prevention of stroke in atrial fibrillation (AF) has changed the clinical management of AF. To inform decision making around dabigatran by identifying factors influencing cost-effectiveness results, we undertook a systematic review of economic evaluations of dabigatran versus warfarin for the prevention of stroke in AF patients. A systematic literature search of Ovid Medline and Embase, Wiley's Cochrane Library, HEED, PubMed databases and grey literature was carried out for primary economic evaluations comparing dabigatran versus warfarin in patients with AF. Data on study characteristics, model inputs and results, and sensitivity analyses were abstracted and synthesized qualitatively. Twenty-three economic evaluations were identified and RE-LY was cited in 52% of studies as the source of the efficacy data. Twenty evaluations used Markov modelling, 2 performed discrete event simulation, and 1 was a trial-based evaluation. Eighty-two percent reported base case incremental cost-effectiveness ratios (ICERs) of less than $50,000 USD/QALY. Key variables, including international normalized ratio (INR) control, the cost of monitoring, risk of stroke and bleeding, and age were found to alter the conclusions in only a few studies. Less commonly explored factors included time horizon and cost of long-term care follow-up. Several factors should be considered when interpreting the results of economic analyses which are based on randomized clinical trial evidence. Real-world data are needed to further assess the clinical and economic consequences of dabigatran relative to warfarin for the prevention of stroke in AF.

Efficacy of Dabigatran Etexilate in a Murine Model of Cancer Associated Thrombosis

Venous thromboembolism (VTE) is a common condition leading to significant patient morbidity and mortality. Thrombosis is a leading direct cause of death in cancer patients with fatal pulmonary embolism being three times more common in cancer patients than in non-cancer patients. In the presence of cancer, recurrent VTE is common and bleeding is particularly problematic due to the use of anticoagulants and the frequent need for surgical interventions. However the therapeutic options for the management of VTE in patients with cancer are limited. The treatment of cancer associated thrombosis (CAT) consists primarily of low molecular weight heparin (LMWH). However, LMWH can only be given parentally and an orally administered medication can have great benefits in improving the quality of life and compliance of patients with malignancies who suffer from VTE. Recently, New Oral Anticoagulants (NOACs) have become available. The advantages of NOACs are that they require less dose adjustment and are given orally. Particularly, during VTE treatment with dabigatran, the incidence of bleeding during VTE treatment is reduced without compromising efficacy. A recent metaanalysis of cancer patients treated with NOACs for VTE demonstrate that NOACs were as effective and safe as warfarin. However, no studies have directly studied NOACs in cancer patients nor compared NOACs with LMWH with selective inclusion of cancer patients only. Dabigatran etexilate (DE), a direct thrombin inhibitor, is one of the NOACs, which has a rapid onset of action and is characterized by its low potential for drug-drug interactions. Treatment with DE can have a significant impact on the burden of care in patients with CAT as it is orally administered and is associated with a lower incidence of bleeding during treatment for VTE. METHODSWe have developed an in vivo murine model of VTE as well as CAT. Thrombus formation is induced in the inferior vena cava (IVC) using the recently described partial flow restriction model and monitored via real time ultrasound using the Vevo770® microimaging system. The importance of our VTE murine model is the non-invasive real-time imaging technique, similar to what is used in clinical practice, making this model an ideal tool for in vivo drug testing. For the CAT model, lymphoma is induced in vivo using murine B lymphoma cells (Eµ-Myc cells) administered intravenously via the tail vein (1 x 106 cells/mouse). ); lymphoma development is attained after six days and inguinal lymph node size is measured via the Vevo770®. Thrombosis is then induced as described above. Anticoagulation is started 24 hours after thrombosis induction, with either dalteparin (LMWH) at a dose of 200 U/kg/day subcutaneously (or vehicle control) or with Dabigatran at a dose of 45 mg/kg/day by oral gavage (or vehicle control). Thrombosis size is then remeasured after 3 days of anticoagulation. RESULTSBoth dalteparin and dabigatran etexilate are effective in reducing the size of the thrombus in our VTE and CAT murine models, although the efficiency differs between cancer and non-cancer associated thrombosis. In our VTE model, daltiparin reduces thrombus size by 32% as compared to 18% for dabigatran, whereas, in our CAT model, dalteparin reduces thrombus size only 11% as compared to 24.9% with dabigatran. CONCLUSIONUsing in vivo murine models, dalteparin is more effective as compared to dabigatran in VTE not associated with cancer whereas the effectiveness of dabigatran is superior in CAT. As a proof of principle, the above described models can be further employed to study the pathophysiology of VTE and CAT and can provide biologic plausibility for pursuing further studies for using NOACs, specifically Dabigatran, in CAT. DisclosuresVanryn:boehringer-Ingelheim: Employment. Blostein:boehringer-ingelheim: Research Funding.

Comparative effectiveness of dabigatran and rivaroxaban versus warfarin for the treatment of non-valvular atrial fibrillation

BackgroundEffectiveness data on novel oral anticoagulants (NOACs) versus warfarin for stroke prevention in non-valvular atrial fibrillation (NVAF) by prior warfarin use are limited. MethodsWe used data from the US MarketScan databases from 2009 to 2012. NVAF patients initiating dabigatran or rivaroxaban were matched with up to 5 warfarin users. Propensity score-adjusted Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for relevant endpoints in NOACs versus warfarin users. Separate analyses were conducted to compare anticoagulant-naïve users of NOACs and those switching from warfarin. ResultsAmong 32,918 dabigatran, 3301 rivaroxaban, and 109,447 warfarin users with NVAF, 225 intracranial bleeds, 1035 ischemic strokes, 958 myocardial infarctions, and 1842 gastrointestinal bleeds were identified. Compared to warfarin users, patients initiating NOACs had similar ischemic stroke rates and lower intracranial bleeding rates, while the gastrointestinal bleeding rate was higher in dabigatran users than warfarin users. Associations of dabigatran with ischemic stroke risk differed between anticoagulant-naïve initiators and patients switching from warfarin; dabigatran was associated with lower ischemic stroke rates in naïve users (HR 0.65, 95% CI 0.52–0.82) but not in switchers (HR 1.20, 95% CI 0.95–1.51), compared to warfarin. Risk of stroke and bleeding was not different between rivaroxaban and warfarin users. ConclusionsReal-world effectiveness of NOACs (compared to warfarin) for diverse outcomes was comparable to efficacy reported in published clinical trials. However, harms and benefits of switching from warfarin to dabigatran need to be evaluated.

Direct Comparison of Dabigatran, Rivaroxaban, and Apixaban for Effectiveness and Safety in Nonvalvular Atrial Fibrillation

The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) has been a major advance for stroke prevention in atrial fibrillation (AF). Patients and clinicians now have a choice between different NOACs, but there is no direct comparative effectiveness evidence to guide decision-making. We aimed to compare the effectiveness and safety of dabigatran, rivaroxaban, and apixaban in clinical practice. Using a large US administrative claims database, we created three one-to-one propensity-score-matched cohorts of patients with nonvalvular AF who were users of dabigatran, rivaroxaban, or apixaban between October 1, 2010 and February 28, 2015 (rivaroxaban vsdabigatran, n= 31,574; apixaban vsdabigatran, n= 13,084; and apixaban vsrivaroxaban, n= 13,130). The primary outcomes were stroke and systemic embolism (effectiveness) and major bleeding (safety) that occurred during treatment. Cox proportional hazards models were used to compare outcomes in propensity-score-matched cohorts. We found no differences between the three NOACs in the risk of stroke or systemic embolism (hazard ratio [HR], 1.00; 95%CI, 0.75-1.32 for rivaroxaban vsdabigatran; HR, 0.82; 95%CI, 0.51-1.31 for apixaban vsdabigatran; and HR, 1.05; 95%CI, 0.64-1.72 for apixaban vsrivaroxaban). Apixaban was associated with a lower risk of major bleeding (HR, 0.50; 95%CI, 0.36-0.70; P< .001 vsdabigatran and HR, 0.39; 95%CI, 0.28-0.54; P< .001 vsrivaroxaban). Rivaroxaban was associated with an increased risk of major bleeding (HR, 1.30; 95%CI, 1.10-1.53; P< .01) and intracranial bleeding (HR, 1.79; 95%CI, 1.12-2.86; P<.05) compared with dabigatran. Dabigatran, rivaroxaban, and apixaban appear to have similar effectiveness, although apixaban may be associated with a lower bleeding risk and rivaroxaban may be associated with an elevated bleeding risk.

Effectiveness and safety of dabigatran versus warfarin in “real-world” Japanese patients with atrial fibrillation: A single-center observational study

BackgroundIn “real-world” practice, anticoagulant therapy is indicated for patients whose clinical profiles are not addressed in randomized clinical trials. We assessed the effectiveness and safety of dabigatran versus warfarin in “real-world” Japanese patients with non-valvular atrial fibrillation (NVAF). MethodsAmong 613 NVAF patients who initiated dabigatran or warfarin therapy during the period between 2011 and 2013, 362 patients were included in the study after propensity score adjustment. The median follow-up period was 1.3 years. The effectiveness and safety outcomes were thromboembolism and major bleeding, respectively. ResultsThe propensity-matched hazard ratios of thromboembolism and major bleeding with dabigatran were 1.03 (95% CI: 0.12-8.04, p=0.971) and 0.15 (95% CI: 0.01–0.90, p=0.037), respectively. ConclusionsThe ability of dabigatran to prevent thromboembolism is comparable to that of warfarin; however, the major bleeding rate is lower with dabigatran in “real-world” NVAF patients.

Abstract 17137: Safety and Effectiveness of Dabigatran Relative to Warfarin in Routine Clinical Practice - New Interim Results of Long-term Study Program

Background: Dabigatran etexilate is a newer oral anticoagulant developed as an alternative to warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Although the efficacy and safety of dabigatran were established in a randomized trial, evaluation of its effects in routine clinical practice is ongoing. Objectives: Quantification of the comparative safety and effectiveness of dabigatran in routine care within two large US commercial health insurance databases (Truven MarketScan and Optum Clinformatics) Methods: Cohort design with propensity score (PS) matching to compare new initiators of dabigatran with warfarin between October 2010 and June 2013. Primary outcomes were stroke and major bleeding. Proportional hazards regression of time to outcome was conducted separately within each data source and results were pooled. Results: There were 22,736 PS matched dabigatran and warfarin initiators with NVAF pooled across data sources (MarketScan 18,726; Optum 4,010). The matching resulted in well balanced cohorts with no individual characteristic (including stroke and bleeding risk factors) having a standardized difference of greater than 0.1. The average follow-up for the as-treated analyses was 5 months for dabigatran and 4 months for warfarin. There were 69 strokes amongst dabigatran initiators and 84 strokes amongst warfarin initiators for a pooled HR of 0.71 (95% CI 0.51 – 0.98) (MarketScan HR = 0.65, 95% CI=0.45-0.93, Clinformatics HR = 1.05, 95% CI = 0.50-2.19). For the outcome of major hemorrhage, there were 429 events amongst dabigatran initiators and 480 events amongst warfarin initiators for a pooled HR of 0.77, 95% CI = 0.68 – 0.88) (MarketScan HR = 0.80, 95% CI = 0.70 - 0.92, Clinformatics HR = 0.55, 95% CI = 0.37 - 0.82). Pooled results in the full cohort were fairly consistent across numerous subgroup and sensitivity analyses, however, comparative conclusions within some subgroups are limited by small numbers and limited follow-up time. Conclusions: Analyses from this ongoing sequential long-term study program suggest a reduced risk of both stroke and major hemorrhage for dabigatran relative to warfarin. Continued follow-up will increase the sample size, permitting greater precision in effect estimates.

Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry.

The effectiveness and safety of dabigatran for stroke prevention in atrial fibrillation (SPAF) demonstrated in RE-LY needs to be confirmed in daily care. To evaluate treatment persistence, effectiveness and safety of dabigatran therapy in SPAF patients in daily care, we used data from an ongoing, prospective, non-interventional registry of more than 2,500 patients on novel oral anticoagulants in daily care. Between October 1, 2011 and February 28, 2013, a total of 341 SPAF patients receiving dabigatran were enrolled. The combined endpoint of stroke/transient ischaemic attack/systemic embolism occurred at a rate of 2.93/100 patient-years in the intention-to-treat analysis (95%-CI 1.6-4.9) and at 1.9/100 patient-years in the on treatment analysis (events within three days after last intake). On-treatment rates were higher in patients selected for 110 mg dabigatran (n=183) BID compared to the 158 patients selected for 150 mg BID (2.88 [95% CI 1.16- 5.93] vs 0.86/100 patient-years [95% CI 0.10, 3.12]). On treatment, major bleeding occurred at a rate of 2.3/100 patient-years and numerically more often in patients receiving the 110 mg BID dose compared to the 150 mg BID dose (2.9 vs 1.7/100 patient-years). Dabigatran treatment discontinuation occurred in a total of 124 patients during follow-up (25.8 per 100 patient-years in Kaplan Meier analysis). Main reasons for treatment discontinuation were non-bleeding side effects. Our data contribute to the confirmation of effectiveness and relative safety of dabigatran in unselected patients in daily care. However, discontinuation rates are not lower than those reported for patients treated with vitamin K antagonists.

A Mixed Treatment Comparison (Mtc) to Compare the Efficacy of Anti-Thrombotic Agents in the Acute Treatment of Venous Thromboembolism (Vte) in Patients with Active Cancer

New oral anticoagulants (NOACs) are available for the treatment and prevention of VTE but evidence on their clinical effectiveness compared with existing treatments is limited. This research compared the clinical effectiveness of dabigatran, rivaroxaban, adjusted standard dose warfarin (warfarin), and low molecular weight heparin (LMWH) in people with active cancer following VTE. This research was conducted during a review of the company’s submission (CS) to the National Institute for Health and Care Excellence (NICE) Single Technology Appraisal programme for the oral direct thrombin inhibitor, dabigatran. Randomised controlled trials (RCTs) for inclusion were identified using the CS for dabigatran (as part of Technology Appraisal [TA]327), and two similar submissions for rivaroxaban (TA261 and TA287). RCTs were assessed for comparability based on patient population, disease severity, and treatments received. A Bayesian MTC was conducted, and fixed and random effects models were explored. Odds ratio (OR) was chosen as the summary statistic for VTE recurrence and major bleed. The network of 9 RCTs formed a “radiating star”. The fixed effects model had the lowest deviance information criterion (DIC) for VTE recurrence and major bleed and so was chosen as the best-fitting model. There was reasonable agreement between the number of unconstrained data points and the residual deviance for both outcomes. Results compared to dabigatran were (OR>1 favours dabigatran): VTE recurrence LMWH OR 0.96 (95% Credible Interval [95%CrI]: 0.15–3.37), rivaroxaban OR 1.29 (95%CrI: 0.12–5.42), warfarin OR 1.87 (95%CrI: 0.31–6.45); major bleed LMWH OR 0.85 (95%CrI: 0.15–2.67), warfarin OR 0.74 (95%CrI: 0.15–2.15). No data were available on major bleed for rivaroxaban in people with active cancer. There were no significant differences in the outcomes evaluated. However, the available evidence suggests that LMWH may have the lowest risk of VTE recurrence in the treatments assessed.

Matching on the disease risk score in comparative effectiveness research of new treatments.

We use simulations and an empirical example to evaluate the performance of disease risk score (DRS) matching compared with propensity score (PS) matching when controlling large numbers of covariates in settings involving newly introduced treatments. We simulated a dichotomous treatment, a dichotomous outcome, and 100 baseline covariates that included both continuous and dichotomous random variables. For the empirical example, we evaluated the comparative effectiveness of dabigatran versus warfarin in preventing combined ischemic stroke and all-cause mortality. We matched treatment groups on a historically estimated DRS and again on the PS. We controlled for a high-dimensional set of covariates using 20% and 1% samples of Medicare claims data from October 2010 through December 2012. In simulations, matching on the DRS versus the PS generally yielded matches for more treated individuals and improved precision of the effect estimate. For the empirical example, PS and DRS matching in the 20% sample resulted in similar hazard ratios (0.88 and 0.87) and standard errors (0.04 for both methods). In the 1% sample, PS matching resulted in matches for only 92.0% of the treated population and a hazard ratio and standard error of 0.89 and 0.19, respectively, while DRS matching resulted in matches for 98.5% and a hazard ratio and standard error of 0.85 and 0.16, respectively. When PS distributions are separated, DRS matching can improve the precision of effect estimates and allow researchers to evaluate the treatment effect in a larger proportion of the treated population. However, accurately modeling the DRS can be challenging compared with the PS.

Effectiveness and Safety of Dabigatran and Warfarin in Real‐World US Patients With Non‐Valvular Atrial Fibrillation: A Retrospective Cohort Study

BackgroundThe recent availability of dabigatran, a novel oral anticoagulant, provided a new treatment option for stroke prevention in atrial fibrillation beyond warfarin, the main therapy for years. Little is known about their real‐world comparative effectiveness and safety, even less among patient demographic and clinical subgroups.Methods and ResultsUsing a cohort of non‐valvular AF patients initiating anticoagulation from October 2010 to December 2012 drawn from a large US database of commercial and Medicare supplement claims, we applied propensity score weights to Cox proportional hazards regression to assess the comparative effectiveness and safety of dabigatran versus warfarin. Analyses were repeated among clinical and demographic subgroups using stratum‐specific propensity scores as an exploratory analysis. Of the 64 935 patients initiating anticoagulation, 32.5% used dabigatran. Compared with warfarin, dabigatran was associated with a lower risk of ischemic stroke or systemic embolism (composite adjusted Hazard Ratio [aHR], 95% CI: 0.86, 95% CI: 0.79 to 0.93), hemorrhagic stroke (aHR: 0.51, 0.40 to 0.65), and acute myocardial infarction (aHR: 0.88, 95% CI: 0.77 to 0.99), and no relation was seen between dabigatran and the composite harm outcome (aHR: 0.94, 95% CI: 0.87 to 1.01). However, dabigatran was associated with a higher risk of gastrointestinal bleeding (aHR: 1.11, 95% CI: 1.02 to 1.22). Estimates of effectiveness and safety appeared to be mostly similar across subgroups.ConclusionsDabigatran could be a safe and potentially more effective alternative to warfarin in patients with atrial fibrillation managed in routine practice settings.

Effectiveness and Safety of Dabigatran and Warfarin in Real-World US Patients With Non-Valvular Atrial Fibrillation: A Retrospective Cohort Study

Effectiveness and Safety of Dabigatran and Warfarin in Real-World US Patients With Non-Valvular Atrial Fibrillation: A Retrospective Cohort Study

Abstract 20218: Comparative Effectiveness of Dabigatran and Rivaroxaban versus Warfarin in Patients With Non-Valvular Atrial Fibrillation

Background: In randomized trials, the new oral anticoagulants (NOAC) dabigatran and rivaroxaban have been at least as efficacious as warfarin in the prevention of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Information on the effectiveness of NOACs versus warfarin in real-world populations in the US is more limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases in the period 2010-12. We selected patients initiating oral anticoagulants after NVAF diagnosis, and with at least 6 months of enrollment before first anticoagulant use. Patients initiating dabigatran or rivaroxaban were matched with up to 5 warfarin users by age, sex, and time in the database. Outcomes of interest (ischemic stroke, intracranial bleeding, and gastrointestinal [GI] bleeding) were defined according to validated algorithms. Information on other comorbidities and medication use was obtained from inpatient, outpatient, and pharmacy claims. High-dimensional propensity score-adjusted Cox proportional hazards regression was used to estimate the association of NOACs vs warfarin with each outcome of interest. Results: The analysis included 32,918 dabigatran, 3,301 rivaroxaban and 92,633 warfarin users with NVAF. During an average 13-month follow-up (6 for rivaroxaban, 15 for dabigatran), 1035 ischemic strokes, 225 intracranial bleeds, and 1842 GI bleeds were identified. Rate of ischemic stroke was similar in patients initiating NOACs compared to those on warfarin. However, rate of intracranial bleeding was lower in patients using NOACs compared to warfarin users, while GI bleeding rate was higher in dabigatran users than warfarin users (Table). Conclusion: In this large real-world patient population, effectiveness of NOACs (compared to warfarin) for diverse outcomes was comparable to efficacy reported in the RE-LY and ROCKET-AF trials.

Abstract 18353: The Comparative Safety and Effectiveness of the Oral Anticoagulant (OAC) Dabigatran versus Warfarin Utilized in a Large Healthcare System in Non-valvular Atrial Fibrillation (NVAF) Patients

Objectives: This study evaluated the safety and effectiveness of dabigatran versus warfarin for stroke risk reduction in NVAF patients in routine clinical care using the Department of Defense Military Health System database. Methods: In this retrospective cohort study, patients were included if they had an AF diagnosis within 12 months prior to first OAC treatment, were 18-89 years, and had a first prescription claim for either dabigatran or warfarin between 01-Oct-2010 and 31-Jul-2012 (index date). Patients were excluded if they had heart valve disorders or prosthetic heart valves, transient causes of AF, or any OAC use during the baseline period. Patients were censored when their prescriptions exceeded a 30 day allowable gap, at OAC switch, at disenrollment, at death, or at study end. A total of 14,813 dabigatran and 24,500 warfarin patients were available for propensity score matching (PSM). PSM based on baseline demographics and clinical characteristics was achieved 1:1 with 12,793 matched subjects per group (within a 0.20 caliper of standard deviation). Comparisons of safety and effectiveness outcomes were made based on Cox-proportional hazards models of PSM groups. All FDA-approved dosages were included in this analysis. Results: Results are summarized in Table 1. Conclusions: Hazard ratios in the post-PSM dabigatran cohort suggest that there is a lower likelihood for stroke, hemorrhagic stroke, major intracranial bleeding, major urogenital and other bleeding, MI, and death than in the warfarin cohort. The hazard ratio in the post-PSM dabigatran cohort suggests a higher likelihood for major lower GI bleeding, but a lower likelihood for intracranial, urogenital, and other bleeding than seen with warfarin. These results are generally consistent with findings of the randomized controlled clinical trial, RE-LY, and support that the benefits of dabigatran demonstrated in clinical trials also may be achieved in a broad population receiving routine clinical care.

PCV77 - Cost Effectiveness Of Apixaban, Dabigatran Rivaroxaban And Warfarin For Atrial Fibrillation In Guatemala

Atrial Fibrillation (AF) affects 1–2% of the population, and this figure is likely to increase in the next 50 years. AF is associated with increased rates of death, stroke and other thromboembolic events, heart failure and hospitalizations, degraded quality of life and reduced exercise capacity. It is suggested that patients with AF should be stratified for the risk of stroke and bleedings and that most should receive antithrombotic therapy. The aim of this study was to assess the cost-effectiveness (CE) of Apixaban against other anticoagulation therapies for prevention on non-valvular atrial fibrillation (NVAF), from the private health care perspective. A simulated cohort of 1000 patients with NVAF entered a decision-tree model to compare costs and effectiveness of Warfarin (5 mg/24 hours), Apixaban (5 mg/12 hours), Dabigatran (110 mg/12 hours and 150 mg/12 hours), and Rivaroxaban (20 mg/24 hours). Effectiveness measures were: stroke, bleeding, myocardial infarction (MI) rates and deaths. Local costs were gathered from Guatemala’s official databases (US$, 2013) and only direct medical costs were considered. The model used a lifetime horizon with a 5% discount. Apixaban was the only treatment that consistently prevented all four considered diseases: 3 MIs, 4 strokes, 85 bleedings and 1 SE avoided when compared to Warfarin. Overall costs were US$33708.34 for warfarin, US$24538.68 for Apixaban, US$24757.57 for Dabigatran 110 mg, US$24198.23 for Dabigatran 150 mg, and US$24252.46 for Rivaroxaban. In terms of QALY’s, Apixaban earned the highest amount with 5.740, followed by Rivaroxaban, Dabigatran 150 mg, Dabigatran 110 mg and Warfarin. In the CE incremental analysis, Apixaban was a cost-effective option. Apixaban obtained the highest probability of being cost-effective (45%) with a 3 GPB per capita in Guatemala. Apixaban is a Cost-Effective option for the Guatemala’s Private Health System.

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.