Treatment Of Non-valvular Atrial Fibrillation Research Articles

Quality of vitamin K antagonist oral anticoagulation in 322 patients with atrial fibrillation - real-life data from a survey in Eastern Switzerland.

To better appreciate the role of the non-vitamin K oral anticoagulants (NOACs) for patients with non-valvular atrial fibrillation in Switzerland we aimed to assess the quality of vitamin K antagonist (VKA) anticoagulation in daily practice. In a cross-sectional study, clinically stable patients on VKA treatment for non-valvular atrial fibrillation for at least 6 months, documentation of international normalised ratio (INR) values for at least 3 months and with at least two INR values were included. The percentage of INR values within the therapeutic range of 2.0 to 3.0 and the time in therapeutic range (TTR; Rosendaal method) and predictors for these measures of VKA anticoagulation quality were assessed. We studied 332 patients (62% male, mean age 74 ± 9 years) with median (interquartile range) CHA2DS2Vasc and HAS-BLED scores of 4 (3-5) and 3 (2-4) points. The median number of INR values per patient was 8 (5-14), and the average interval between INR measurements was 20 (13-27) days. The percentage of INR values between 2.0 and 3.0 was 67% (50-83%). The median TTR was 69% (51-89%), and TTR ≥65% was found in 202 (61%) patients. Independent predictors of ≥80% INR values between 2.0 and 3.0 included a longer interval between INR measurements and the non-use of spironolactone. The non-use of amiodarone and spironolactone and a longer interval between INR measurements were the only independent predictors of a TTR ≥65%. The quality of VKA anticoagulation in Switzerland is highly variable. Importantly, only 60% of patients achieve a TTR ≥65%, which is currently considered to be the minimal acceptable TTR required for VKA therapy. There are few clinical predictors of a good VKA anticoagulation quality. These data may represent a novel basis for decision making regarding the choice of anticoagulation for atrial fibrillation in Switzerland.

Dosing issues with non-vitamin K antagonist oral anticoagulants for the treatment of non-valvular atrial fibrillation: Why we should not underdose our patients

Non-vitaminK antagonist oral anticoagulants (NOACs) -dabigatran, rivaroxaban, apixaban and edoxaban- are well established in terms of preventing stroke or systemic embolism in patients with non-valvular atrial fibrillation and high thromboembolism risk. When prescribed incorrectly, NOACs are associated with an increased risk of ischaemic events and bleeding. Current NOAC labels explicitly address dose adjustments according to age, body weight, renal function and concomitant treatment with P-glycoprotein inhibitors. The required dose adjustments vary significantly from molecule to molecule, thereby creating a complex dose adjustment environment. Furthermore, recommendations support assessment of individual risk using thromboembolic and bleeding risk scores. Evidence-based medicine also provides data about specific patient profiles. In particular, some patients who are at higher risk of bleeding, such as patients on polymedication, are often at higher risk of stroke. More and more patients are being treated with NOACs. The question of appropriate dosing has become important, as studies are starting to show that reduced doses are being prescribed at very high rates. Although these data have not been evaluated in light of individual risk assessments, in everyday practice, physicians are often more concerned about drug-related bleeding than about the spontaneous evolution of the disease (stroke/systemic embolism), leading to high rates of prescription of inadequately low doses. Recent results have shown that only certain risk criteria justify dose reduction. Thus, the right dose needs to be prescribed for the right patient in order to obtain, in real-life practice, the benefits of NOACs that have been demonstrated in randomized clinical trials.

Is rivaroxaban a cost-effective anticoagulation therapy compared with warfarin?

Bottom line Yes. For the treatment of atrial fibrillation, patients given rivaroxaban have similar or lower total costs than patients given warfarin (including medications, laboratory costs, hospitalizations, outpatient/emergency visits, and transportation) over the short term (SOR: B, consistent cohort studies). Rivaroxaban is also likely cost effective after 16 years compared with warfarin for treatment of nonvalvular atrial fibrillation (NVAF) (SOR: B, cost-effectiveness simulation). For treatment of venous thromboembolism (VTE), there is a 98% likelihood that rivaroxaban is cost saving compared with warfarin (SOR: B, cost-effectiveness simulation).

Aneurysmal subarachnoid hemorrhage in patients taking direct oral anticoagulants: A case series and discussion of management

Abstract Direct oral anticoagulants are becoming more commonplace for the treatment of nonvalvular atrial fibrillation and deep vein thrombosis. Unfortunately, effective reversal agents are not widely available limiting options for neurosurgical intervention during active anticoagulation. We report a case series of 3 patients treated for aneurysmal subarachnoid hemorrhage while taking direct oral anticoagulants. All three underwent open surgical clipping after adequate time was allowed for drug metabolism. Decision-making must take into account timing of intervention, drug half-life, and currently available reversal agents.

Comparative effectiveness of rivaroxaban in the treatment of nonvalvular atrial fibrillation.

Rivaroxaban is a direct oral anticoagulant (DOAC) approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, a common arrhythmia. In this review, we summarize the effectiveness of rivaroxaban versus warfarin and the DOACs dabigatran, apixaban and edoxaban. The primary focus is on primary evidence from clinical trials, indirect comparison studies and real-world studies. While there are gaps in the literature, the evidence thus far indicates that rivaroxaban is superior to warfarin and similar to dabigatran, apixaban and edoxaban for the prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation, although rivaroxaban may be associated with an elevated bleeding risk compared with other DOACs.

Evaluation of Apixaban for the Treatment of Nonvalvular Atrial Fibrillation With Regard to Dosing and Safety in a Community Hospital.

Background: Apixaban, a direct factor Xa inhibitor, is approved by the US Food and Drug Administration (FDA) for prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Apixaban's compelling safety and efficacy data, combined with minimal laboratory monitoring, make it an attractive anticoagulant. Objectives: To characterize and evaluate the dosing and safety of apixaban for the treatment of nonvalvular atrial fibrillation at a community hospital. Design/Patients: A retrospective chart review evaluated patients ≥18 years of age who received at least 2 consecutive doses of apixaban from January 1, 2013 to June 30, 2016. Patients with multiple admissions were evaluated for each hospitalization. Patients were excluded if height, weight, or serum creatinine was not documented during hospital admission. Patients who received apixaban for the treatment or prophylaxis of venous thromboembolism were excluded. Prescribing patterns were characterized based on FDA-approved dosing regimens and patient demographics. Safety outcomes included incidences of major, clinically relevant nonmajor, and minor bleeding. Results: Of the 707 patients evaluated, 82% received an FDA-approved apixaban regimen. Of the 127 patients (18%) who received an unapproved regimen, 5.5% (7 patients) received an unapproved frequency and 94.5% (120 patients) received an unapproved dose. The majority (98 patients, 81.7%) were underdosed. Composite bleeding rates were 2.7%, with 1.8% major bleeds, 0.7% clinically relevant nonmajor bleeds, and 0.1% minor bleeds. Conclusions: The use of apixaban must be monitored in order to ensure FDA-approved dosing regimens are being prescribed and patients are not being underdosed.

Dabigatran etexilate: appropriate use in patients with chronic kidney disease and in the elderly patients.

Dabigatran etexilate (DE) is a direct thrombin inhibitor, which has been approved for the treatment of non-valvular atrial fibrillation (AF), and for the prevention and treatment of venous thromboembolism (VTE). Despite large randomized clinical trials and independent observational studies providing robust data concerning DE safety and efficacy, some physicians still perceive mild-to-moderate renal impairment and old age as a relative contraindication to its use. In this article, we review the available scientific evidence supporting the use of DE in these clinical situations. Patients with AF and chronic kidney disease (CKD) are per se at high risk of stroke, bleeding and mortality. Although there is evidence of clinical benefit of anticoagulation in these patients, anticoagulant therapy requires caution and demands careful clinical monitoring, regardless of the drug used. In patients with no contraindication to its use, the clinical benefit of DE versus warfarin is independent of renal function. The elderly with AF are frequently undertreated because of the perception of high bleeding risk and limited clinical benefit. However, the clinical benefit of anticoagulation is independent of patient age, and age per se should not represent a contraindication to anticoagulation. DE has been extensively studied in the elderly, both in randomized clinical trials and in observational studies: DE 150mg BID should not be used in patients 80years of age or older, while DE 110mg BID is as safe as warfarin. Intracranial haemorrhages reduction by DE compared with warfarin is preserved in the elderly. Therefore, mild and moderate CKD and being elderly should not deter physicians from prescribing DE. Furthermore, the availability of a specific antidote is expected to improve the safety of the use of DE in clinical practice.

Abstract WP51: Neurological Severity and Infarct Size in Patients With Acute Ischemic Stroke During DOAC Treatment for Nonvalvular Atrial Fibrillation

Background and purpose: Less severe and smaller infarct are features in acute stroke patients treated with warfarin within a therapeutic range of PT-INR than in those without. But it remains unclear the severity and size of infarct in acute stroke patients treated with direct oral anticoagulants [DOAC]. We investigated the features of acute stroke in patients treated with DOAC, warfarin or without. Methods: We enrolled consecutive 190 non-valvular atrial fibrillation patients (mean age 78; 63% male) who developed acute ischemic stroke and classified them into 4 groups, 109 patients with no anticoagulant therapy [Control group], 25 patients with DOAC therapy [DOAC group], 19 patients treated with warfarin within a therapeutic range of PT-INR [>= 1.6 in patients aged 70 years old or older, >= 2.0 in those aged younger than 70 years old, Warfarin well controlled group], and 37 patients treated with warfarin with subtherapeutic PT-INR values [Warfarin not controlled group]. Infarcts sizes were defined as the maximum diameter of infarct, using the brain MRI diffusion-weighted image. Stroke severity on admission were assessed by the National Institutes of Health Stroke Scale[NIHSS].We compared them among the groups. Results: There were no significant differences in preadmission CHADS2 score among the 4 groups. The median infarct size were 31mm (interquartile (IQR) 13-59) in the control group, 10mm (IQR 7.4-38) in the DOAC group, 12mm (IQR 8.0-45) in the warfarin well controlled group, and 24mm (IQR 13-67) in the warfarin not controlled group. The size of infarct was significantly smaller in the DOAC group than the control group (P=0.01). The NIHSS on admission was 4 ([IQR] 2-15) in the control group, 2 (1-6) in the DOAC group, 4 (1-17) in the warfarin well controlled group and 5 (3-17) in e warfarin not controlled group. Stroke severity on admission was also more favorable in the DOAC group when compared with the control group (P=0.03) Conclusions: Smaller and less severe infarct may be feature of acute ischemic stroke during DOAC therapy when compared to that without any anticoagulant therapy.

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.

Preclinical assessment of a modified Occlutech left atrial appendage closure device in a canine model

BackgroundLAA occlusion has a similar stroke prevention efficacy compared to anticoagulation treatment for non-valvular atrial fibrillation. ObjectiveThe objective of this study was to assess the feasibility and safety of a modified Occlutech® left atrial appendage (LAA) closure device in a canine model. MethodsThe device was implanted in 10 dogs (33±1kg) using fluoroscopy and transesophageal echocardiography (TEE) guidance. The modified Occlutech® LAA occlusion device was compared with the current version, the Watchman device, and the Amplazter cardiac plug (ACP). LAA occlusion and anchoring to the LAA were evaluated. All dogs were assessed using angiography, TEE, and a gross anatomy examination. ResultsThe 10 LAA occlusion devices were to be implanted into 10 dogs (5 modified Occlutech devices, 3 current version of Occlutech devices, 1 Watchman, and 1 ACP). LAA implantation was not performed in one dog due to transeptal puncture failure. The three current version of Occlutech devices were embolized immediately after implantation, so three modified devices of the same size were implanted securely without embolization. The mean implant size was 20.1±2.0mm. The devices chosen were a mean of 23.3±10.6% larger than the measured landing zone diameters. Post-implant angiography and TEE revealed well-positioned devices without pericardial effusion or impingement on surrounding structures. ConclusionsThe results of this acute animal study suggested that a modified Occlutech® LAA occlusion device was feasible and had greater anchoring performance in canines. Additional large clinical studies are needed to evaluate safety and efficacy.

DIRECT COMPARISON OF DABIGATRAN, RIVAROXABAN, AND APIXABAN FOR EFFECTIVENESS AND SAFETY IN NONVALVULAR ATRIAL FIBRILLATION

Clinical trials have demonstrated efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in comparison to warfarin for the treatment of non-valvular atrial fibrillation (AF). However, there have been no head-to-head trials comparing the NOACs, and indirect comparison

Management of Major Bleeding with the Non-Vitamin K Oral Anticoagulants: the Role of Antidotes

Over the recent years, new oral anticoagulant agents have been developed and entered the clinical arena, the direct or non-vitamin K oral anticoagulants (NOACs). Although more expensive, these agents have been proven as equivalent or superior to vitamin K antagonists in the treatment of non-valvular atrial fibrillation (AF) and venous thrombo-embolism with a lower incidence of intracerebral hemorrhage. Nevertheless, occurrence of major or life-threatening bleeding events is still quite possible. Thus, there is a major concern regarding the lack of a specific antidote and rapid reversal agent in such disastrous situations. Fortunately, the development of effective specific NOAC antidotes has recently made great advances, which are herein briefly reviewed.

Dabigatran Versus Warfarin for Atrial Fibrillation in Real-World Clinical Practice: A Systematic Review and Meta-Analysis.

Trial data for the benefits and risks of dabigatran versus warfarin in the treatment of nonvalvular atrial fibrillation are lacking. We sought to review real-world observational evidence for the comparative effectiveness and safety of these agents. A systematic search of multiple databases was conducted from first available date to March 10, 2015 for longitudinal, observational studies comparing dabigatran with warfarin. Two reviewers evaluated studies for eligibility and extracted hazard ratios for ischemic stroke and gastrointestinal and intracranial bleeding. hazard ratios were pooled using random-effects meta-analysis. Metaregression was performed to assess treatment-effect heterogeneity. We identified 232 unique citations. Seven retrospective cohort studies met study eligibility criteria, with 348 750 patients and a mean follow-up of 2.2 years. In pooled analyses, dabigatran-150 mg was not superior to warfarin in preventing stroke (hazard ratio, 0.92; 95% confidence interval, 0.84-1.01; P=0.066), but had a significantly lower hazard of intracranial bleeding (0.44; 0.34-0.59; P<0.001). Dabigatran-150 mg had a significantly greater hazard of gastrointestinal bleeding than warfarin (1.23; 1.01-1.50; P=0.041), which was potentiated in studies of older (elderly) versus younger populations (median/mean age, ≥75 versus <75 years; β=1.53; 95% confidence interval, 1.10-2.14; P=0.020). In real-world clinical practice, dabigatran is comparable with warfarin in preventing ischemic stroke among patients with nonvalvular atrial fibrillation. However, dabigatran is associated with a lower risk for intracranial bleeding relative to warfarin, but-particularly among the elderly-a greater risk for gastrointestinal bleeding. Bleeding outcomes from observational studies are consistent with those from the pivotal Randomized Evaluation of Long-Term Anticoagulation Therapy trial.

Thrombelastography detects dabigatran at therapeutic concentrations in vitro to the same extent as gold-standard tests

Background/objectivesDabigatran is an oral anticoagulant approved for treatment of non-valvular atrial fibrillation, deep venous thrombosis (DVT), pulmonary embolism and prevention of DVT following orthopedic surgery.Monitoring of the dabigatran level is essential in trauma and bleeding patients but the available plasma-based assays may not sufficiently display its hemostatic effect.This study investigated the in vitro effect of different concentrations of dabigatran on whole blood thrombelastography (TEG) and its correlation to the specific but time-consuming plasma-based tests Hemoclot and Ecarin Clotting Time (ECT). MethodBlood was collected from 8 healthy donors (two females, six males) with a median age of 46years and it was spiked with dabigatran to a range of plasma concentrations (0, 50, 100, 200 and 400ng/ml) covering the therapeutic level. ResultsMean TEG R at 0ng/ml=5.963min, 50ng/ml=7.425min, 100ng/ml=8.425min, 200ng/ml=9.775min, 400ng/ml=11.813min. A significant overall increase (p=0.001) in TEG reaction time (R) was found across increasing dabigatran concentrations i.e. 0 vs 50 vs 100 vs 200 vs 400ng/ml (p<0.000 p=0.027 p=0.026, p=0.005, respectively). TEG R correlated strongly with Hemoclot (R2=0.891, p<0000) and ECT (R2=0.914, p<0.000) and Hemoclot and ECT were strongly inter-correlated (R2=0.978, p<0.000). ConclusionThe whole blood viscoelastic assay TEG R displayed linearity towards fixed concentrations of dabigatran and correlated strongly to the current gold-standard tests Hemoclot and ECT, for assessing dabigatran. TEG R is applicable as a rapid and precise whole blood monitoring test for dabigatran treated patients in the emergency setting.

Adherence to a Novel Oral Anticoagulant Among Patients with Atrial Fibrillation.

Dabigatran is a direct thrombin inhibitor approved by the FDA in October 2010 for the treatment of nonvalvular atrial fibrillation. Little is known regarding patient adherence to this therapy. To examine adherence and persistence to dabigatran among adults with atrial fibrillation. We used IMS Health's LifeLink Health Plan Claims Database from 2010 to 2012 to identify patients with atrial fibrillation who were new users of dabigatran. We derived adherence and persistence for continuously enrolled patients at 6 months, 9 months, and 12 months of follow-up. We measured adherence using the medication possession ratio (MPR), defined as individuals with MPRs of 0.80 or greater as adherent, and examined persistence by identifying individuals with gaps in drug possession of 60 days or greater. Of 5,951 adults with atrial fibrillation who were new users of dabigatran, 49% had prevalent atrial fibrillation and at least 6 months of continuous follow-up. Of these, 89% used dabigatran as the only oral anticoagulant, whereas the remainder filled prescriptions for at least 1 other oral anticoagulant during the follow-up period. Among those using dabigatran alone (n = 2,713), the mean MPR was 0.73 (standard error = 0.30), 41% were nonadherent with therapy, and 32% had gaps of 60 days or greater. Among those observed for 9 (or 12) months who used dabigatran alone, rates of nonadherence were 47% (49%), whereas 48% (49%) discontinued therapy during follow-up. Rates of adherence and persistence were similar for patients with incident atrial fibrillation. Nonadherence to dabigatran was common among patients with atrial fibrillation. Future studies are needed to understand the reasons for nonadherence.

Meta-Analysis of Renal Function on the Safety and Efficacy of Novel Oral Anticoagulants for Atrial Fibrillation

Novel oral anticoagulants (NOACs) are safe and effective for the prevention of stroke or systemic embolism (S/SE) in atrial fibrillation. The efficacy and safety of NOACs compared with warfarin has not been systematically assessed in subjects with mild or moderate renal dysfunction. We performed a meta-analysis of the randomized clinical trials that compared efficacy and safety (major bleeding) outcomes of NOACs compared to warfarin for the treatment of nonvalvular atrial fibrillation and had available data on renal function. We estimated the pooled relative risk (RR) of S/SE and major bleeding in relation to renal function (assessed by baseline estimated glomerular filtration rate divided in 3 groups: normal [estimated glomerular filtration rate >80 ml/min], mildly impaired [50 to 80 ml/min], and moderate impairment [<50 ml/min]). We included 4 randomized clinical trials enrolling a total of 58,338 subjects. The RRs of S/SE and major bleeding were higher in subjects with renal impairment compared to normal renal function, independent of type of anticoagulant therapy. In subjects with normal renal function, no difference in the risk of S/SE was observed, whereas the risk of major bleeding was slightly lower for subjects taking NOACs (RR 0.87, 95% confidence interval [CI] 0.76 to 0.99). In subjects with mild or moderate renal impairment, NOACs were associated with a reduced risk of S/SE (RR 0.75, 95% CI 0.66 to 0.85 and RR 0.80, 95% CI 0.68 to 0.94, respectively) and major bleeding (RR 0.87, 95% CI 0.79 to 0.95 and RR 0.80, 95% CI 0.71 to 0.91, respectively) compared to warfarin. The pooled analysis for major bleeding demonstrated significant heterogeneity. In conclusion, the use of NOACs was associated with a reduced risk of S/SE and reduced risk of major bleeding compared to warfarin in subjects with mild or moderate renal impairment suggesting a favorable risk profile of these agents in patients with renal disease.

Novel oral anticoagulants vs warfarin for the management of postoperative atrial fibrillation: clinical outcomes and cost analysis

BackgroundThe novel oral anticoagulants (NOACs) apixaban, rivaroxaban, and dabigatran are indicated for the treatment of nonvalvular atrial fibrillation, but their use in patients with postoperative atrial fibrillation (POAF) is less well defined. MethodsAll patients undergoing isolated coronary artery bypass grafting from 2013 to 2015 (n = 598) were studied. Patients with POAF anticoagulated with either warfarin or NOACs were evaluated for differences in length of stay, blood product use, bleeding, and cost of therapy. ResultsThere was no significant difference between the NOAC and warfarin group for any of the clinical outcomes evaluated. Time to therapeutic anticoagulation was significantly longer with warfarin. Neither group had a major bleeding event during the initial hospitalization, but 2 patients in the warfarin group had delayed major bleeding complications. Total costs were significantly reduced in patients treated with NOACs. ConclusionsBoth NOACs and warfarin are safe and effective means of anticoagulation for POAF after coronary artery bypass grafting. Patients were therapeutic more rapidly and with less cost of treatment when NOACs were used.

Factor Xa inhibitors: a novel therapeutic class for the treatment of nonvalvular atrial fibrillation.

Atrial fibrillation is the most common cause of stroke. Treatment with anticoagulants in patients with atrial fibrillation reduces embolic complications of the disease including stroke. However, the commonly used anticoagulant has a narrow therapeutic index, requires routine monitoring, and has numerous drug and food interactions leading to less than optimal rates of adherence. Inhibition of clotting factor Xa has been evaluated as a potential target for anticoagulation therapy with the hypothesis that using target-specific therapy will alleviate some of the dosing variability observed with the vitamin K antagonist. Three factor Xa inhibitors are currently indicated for use in nonvalvular atrial fibrillation. Similar to the vitamin K antagonist, warfarin, all of the factor Xa inhibitors are administered orally. Rivaroxaban and edoxaban are dosed once daily while apixaban is dosed twice daily. All three agents have demonstrated noninferiority when compared with current standard treatment with warfarin for efficacy and safety outcomes. The therapeutic dose of factor Xa inhibitors vary based on renal function. Unlike warfarin, there are no currently available antidotes for the factor Xa inhibitors although this is an area of interest for current and future studies. In the event of a life-threatening bleed there are established management strategies to reverse the bleeding effects of the factor Xa inhibitors.

National Trends in Ambulatory Oral Anticoagulant Use

BackgroundFour direct oral anticoagulants (DOACs) have been brought to market for the treatment of nonvalvular atrial fibrillation and venous thromboembolism. Many forces, including numerous positive trial results, emerging safety concerns, marketing, and promotion, may shape DOAC adoption by providers. However, relatively little is known regarding their ambulatory utilization compared with warfarin, as well as the degree to which they have decreased under-treatment of atrial fibrillation. MethodsWe used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of outpatient office visits, to estimate the use of warfarin and DOACs between 2009 and 2014. ResultsOverall, visits with anticoagulation use increased from 2.05 (95% confidence interval [CI], 1.82-2.27) to 2.83 (95% CI, 2.49-3.17) million (M) quarterly visits (P < .001). Of these, DOAC use has grown to 4.21M (95% CI, 3.63M-4.79M; 38.2% of total) treatment visits in 2014 since their introduction in 2010. Use of all oral anticoagulants in treatment visits for atrial fibrillation has increased from 0.88M (95% CI, 0.74M-1.02M) to 1.72M (95% CI, 1.47M-1.97M; P < .001), with similar DOAC and warfarin use in 2014. Atrial fibrillation visits with anticoagulant use increased from 51.9% (95% CI, 50.4%-53.8%) to 66.9% (95% CI, 65.0%-69.3%) between 2009 and 2014 (P < .001). In 2014, rivaroxaban was the most commonly prescribed DOAC for atrial fibrillation (47.9% of office visits), followed by apixaban (26.5%) and dabigatran (25.5%). ConclusionsDirect oral anticoagulants have been adopted rapidly, matching the use of warfarin, and are associated with increased use of oral anticoagulation for patients with atrial fibrillation.

Net clinical benefit of oral anticoagulants: a multiple criteria decision analysis.

BackgroundThis study quantitatively evaluated the comparative efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, and apizaban) and warfarin for treatment of nonvalvular atrial fibrillation. We also compared these agents under different scenarios, including population with high risk of stroke and for primary vs. secondary stroke prevention.MethodsWe used multiple criteria decision analysis (MCDA) to assess the benefit-risk of these medications. Our MCDA models contained criteria for benefits (prevention of ischemic stroke and systemic embolism) and risks (intracranial and extracranial bleeding). We calculated a performance score for each drug accounting for benefits and risks in comparison to treatment alternatives.ResultsOverall, new agents had higher performance scores than warfarin; in order of performance scores: dabigatran 150 mg (0.529), rivaroxaban (0.462), apixaban (0.426), and warfarin (0.191). For patients at a higher risk of stroke (CHADS2 score≥3), apixaban had the highest performance score (0.686); performance scores for other drugs were 0.462 for dabigatran 150 mg, 0.392 for dabigatran 110 mg, 0.271 for rivaroxaban, and 0.116 for warfarin. Dabigatran 150 mg had the highest performance score for primary stroke prevention, while dabigatran 110 mg had the highest performance score for secondary prevention.ConclusionsOur results suggest that new oral anticoagulants might be preferred over warfarin. Selecting appropriate medicines according to the patient’s condition based on information from an integrated benefit-risk assessment of treatment options is crucial to achieve optimal clinical outcomes.