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It remains unknown whether the comparative effectiveness of direct oral anticoagulants (DOACs) and warfarin differs between atrial fibrillation patients with and without a history of stroke or transient ischemic attack (TIA). Using 2012 to 2014 Medicare claims data, we identified patients newly diagnosed with AF in 2013 to 2014 who initiated apixaban, dabigatran, rivaroxaban, or warfarin. We categorized patients based on a history of stroke or TIA. We constructed Cox proportional hazard models that included indicator variables for treatment groups, a history of stroke or TIA, and the interaction between them, and controlled for demographics and clinical characteristics. DOACs were generally more effective than warfarin in stroke prevention; however, there were important differences between subgroups defined by a history of ischemic stroke. In particular, the superiority of dabigatran compared with warfarin in ischemic stroke prevention was more pronounced in patients with a history of stroke or TIA (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.48 to 0.85) than in patients with no history of stroke or TIA (HR 0.94; 95% CI 0.75 to 1.16; p value for interaction = 0.034). There was no difference in the risk of stroke between apixaban, dabigatran, and rivaroxaban in patients with no history of stroke or TIA. However, in patients with a history of stroke or TIA, the risk of stroke was lower with dabigatran (HR 0.64; 95% CI 0.48 to 0.85) and rivaroxaban (HR 0.70; 95% CI 0.56 to 0.87), compared with apixaban (p value for both interactions <0.05). In conclusion, the comparative effectiveness of DOACs differs substantially between patients with and without a history of stroke or TIA; specifically, apixaban is less effective in patients with a history of stroke or TIA., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: Less than half of US patients with a diagnosis of atrial fibrillation (AF) receive oral anticoagulation., Objectives: To identify patients with similar patterns of adherence to regimens of warfarin and direct oral anticoagulants (DOACs) in the first year after AF diagnosis and to evaluate associations between patient characteristics and membership in latent classes of adherence., Design, Setting, and Participants: This retrospective cohort study used 2013 to 2016 Medicare claims data to identify 7491 patients with a new diagnosis of AF in 2014 to 2015 who initiated warfarin after AF diagnosis and 9478 patients with a new diagnosis of AF in 2014 to 2015 who initiated DOAC treatment after AF diagnosis, for a total of 16 969 Medicare beneficiaries. Participants were followed up for 12 months after AF diagnosis. Statistical analysis was performed from February 1 to November 30, 2018., Exposures: Treatment with warfarin or DOAC after AF diagnosis., Main Outcomes and Measures: The main outcome was the proportion of days that patients received warfarin or DOAC, measured in 30-day intervals after AF diagnosis. Independent variables included patient demographic characteristics, socioeconomic status, region of residence, and clinical characteristics. Latent class mixed models were used to identify latent classes of warfarin and DOAC adherence, and polytomous logistic regression was used to assess the association between patient characteristics and membership in each latent class., Results: Among the 7491 patients receiving warfarin (4348 women), the mean (SD) age was 76.0 (10.0) years; among the 9478 patients receiving DOAC (5496 women), the mean (SD) age was 77.0 (8.5) years. Four latent classes of patients were identified based on warfarin adherence: late initiators (980 [13%]), early initiators who discontinued therapy at months 1 to 3 (1297 [17%]) or at months 5 to 10 (735 [10%]), and continuously adherent patients (4479 [60%]). Four latent classes of patients were also identified based on DOAC adherence: patients who initiated DOAC in months 1 to 5 (1368 [14%]) or months 6 to 11 (800 [8%]), patients with suboptimal and decreasing adherence (2267 [24%]), and continuously adherent patients (5043 [53%]). Membership in latent classes of warfarin adherence was significantly associated with sex, eligibility for Medicaid and income subsidy, region of residence, CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age 65-74 [1 point] or ≥75 years [2 points], diabetes, and stroke, transient ischemic attack or thromboembolism [2 points]-vascular disease, and sex category [female]) risk score, and HAS-BLED (hypertension, abnormal renal and liver function, stroke, bleeding, labile international normalized ratio, elderly, and drugs or alcohol) score. Membership in latent classes of DOAC adherence was significantly associated with race/ethnicity, region of residence, HAS-BLED score, and use of antiarrhythmic medications., Conclusions and Relevance: This study found that, among patients who initiated anticoagulation therapy, 40% of those who initiated warfarin therapy and 47% of those who initiated DOAC treatment did not continuously adhere to therapy in the first year after AF diagnosis. Identifying longitudinal patterns of warfarin and DOAC adherence and the factors associated with them provides suggestions for the design of targeted strategies to mitigate suboptimal oral anticoagulation use.

Background: Several studies have compared the cost effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin using results from clinical trials evaluating NOACs. However, the time in therapeutic range (TTR) of warfarin groups ranged across clinical trials, and all were below the therapeutic goal of 70%. We compared the cost effectiveness of edoxaban 60 mg, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, rivaroxaban 20 mg, and well-managed warfarin with a TTR of 70% in preventing stroke among patients with atrial fibrillation at high risk of bleeding., Methods: For the six treatments, we used a Markov state-transition model to quantify lifetime costs in $US and effectiveness in quality-adjusted life-years (QALYs). We simulated relative risk ratios of clinical events with each NOAC versus warfarin with a TTR of 70% using published regression models that predict how the incidence of thrombotic or hemorrhagic events changes for each unit change in TTR. We re-ran our analysis for two other estimates of TTR: 65 and 75%., Results: Treatment with edoxaban 60 mg cost $US127,520/QALY gained compared with warfarin with a TTR of 70% and cost $US41,860/QALY gained compared with warfarin with a TTR of 65%. However, warfarin with a TTR of 75% was more effective and less expensive than all NOACs. For three levels of TTR, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, and rivaroxaban 20 mg were dominated strategies., Conclusions: The comparative cost effectiveness of edoxaban and warfarin is highly sensitive to TTR. At the $US100,000/QALY willingness-to-pay threshold, our results suggest that warfarin is the most cost-effective treatment for patients who can achieve a TTR of 70%.

The objective of the study was to examine how the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin differ across subgroups of patients with atrial fibrillation defined by stroke risk (CHA2DS2-VASc score ≤3, 4 to 5, ≥6). Using Medicare claims data, we identified patients newly diagnosed with atrial fibrillation in 2013 to 2014 who initiated warfarin (n=12,354), apixaban (n=2,358), dabigatran (n=1,415), or rivaroxaban (n=5,139), and categorized them according to their CHA2DS2-VASc score (≤3, 4 to 5, ≥6). Primary outcomes included the combined risk of ischemic stroke, other thromboembolic event and death, and the risk of bleeding. We constructed Cox proportional hazard models that included terms for treatment, CHA2DS2-VASc subgroup, and the interaction between them, and controlled for demographics and a comprehensive list of clinical characteristics. We found that DOACs were generally more effective than warfarin, but this effect was most pronounced in the lowest risk subgroup. Specifically, the hazard ratio for the primary effectiveness outcome with apixaban compared with warfarin was 0.46 (95% confidence interval [CI] 0.32 to 0.65) for CHA2DS2-VASc ≤3, 0.71 (95% CI 0.61 to 0.86) for 4 to 5, and 0.86 (95% CI 0.74 to 1.01) for ≥6 (p value for interaction = 0.005). The comparative safety profile of DOACs versus warfarin did not change with CHA2DS2-VASc score. In conclusion, DOACs are more effective than warfarin, but this effect is more pronounced in patients with lower risk of stroke. Further research is needed to validate these findings in other patient cohorts and uncover their underlying mechanisms., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and Purpose: Little is known about the clinical outcomes associated with posthemorrhage anticoagulation resumption for atrial fibrillation. This study had 2 objectives: first, to evaluate anticoagulation use after a first major bleed on warfarin or dabigatran and, second, to compare effectiveness and safety outcomes between patients discontinuing anticoagulation after a major bleed and patients restarting warfarin or dabigatran., Methods: Using 2010 to 2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding event while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their posthemorrhage use of anticoagulation. We followed them until an ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors affecting anticoagulation resumption and Cox proportional hazard models to compare the combined risk of ischemic stroke and all-cause mortality and the risk of recurrent bleeding between treatment groups., Results: Resumption of anticoagulation with warfarin (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.59-0.97) or dabigatran (HR 0.66; 95% CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients prescribed warfarin after the event than for those prescribed dabigatran (HR 2.31; 95% CI 1.19-4.76) or whose anticoagulation ceased (HR 1.56; 95% CI 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation (HR 0.65; 95% CI 0.32-1.33)., Conclusions: Dabigatran was associated with a superior benefit/risk ratio than warfarin and anticoagulation discontinuation in the treatment of atrial fibrillation patients who have survived a major bleed., (© 2016 American Heart Association, Inc.)

Importance: It remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice., Objective: To compare the risk of bleeding associated with dabigatran and warfarin using Medicare data., Design, Setting, and Participants: In this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011., Exposures: Dabigatran users (n = 1302) and warfarin users (n = 8102)., Main Outcomes and Measures: We identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities., Results: Dabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of major bleeding among dabigatran users was especially high for African Americans and patients with chronic kidney disease., Conclusions and Relevance: Dabigatran was associated with a higher incidence of major bleeding (regardless of the anatomical site), a higher risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage. Thus, dabigatran should be prescribed with caution, especially among high-risk patients.

Background: Nonadherence to oral anticoagulants (OACs) is a challenge to stroke risk reduction in patients with nonvalvular atrial fibrillation (NVAF). Data on primary medication nonadherence (PMN) in NVAF are lacking. Objectives: Our aim was to assess the rates and predictors of PMN among NVAF patients who were newly prescribed an OAC. Methods: This was a retrospective database analysis of linked healthcare claims and electronic health record data. Adult NVAF patients with a prescription order for an OAC (apixaban, rivaroxaban, dabigatran, or warfarin) between January 2016 and June 2019 were identified (date of first prescription order = index date). Patients had a 1-year baseline and a 6-month post-index period to assess the rates of PMN, defined as having a prescription order but no paid claim for any OAC on or within 30 days after the index date. Sensitivity analyses explored 60-, 90- and 180-day PMN thresholds. Logistic regression models were used to examine the predictors of PMN. Results: Among 20,393 patients, the overall 30-day PMN rate was 28.4%; PMN rates decreased to 17% with a 180-day threshold. PMN was numerically lowest for warfarin among OACs and numerically lowest for apixaban among direct OACs. A CHA2DS2-VASc score of ≥ 3, commercial insurance, and African American race were associated with higher odds of PMN. Conclusions: More than one-quarter of patients experienced PMN within 30 days of their initial prescription order. This rate decreased over a longer period, suggesting a delay in fills. Understanding the factors associated with PMN is warranted to develop effective interventions for improving OAC treatment rates in NVAF. [ABSTRACT FROM AUTHOR]

Background: In patients with atrial fibrillation (AF) who survive an anticoagulant-related intracranial hemorrhage (ICH), the benefits of restarting oral anticoagulation (OAC) remain unclear. Objective: In this study, we sought to determine the effectiveness and safety associated with resumption of OAC in atrial fibrillation patients who survive an ICH. Methods: Using 2010–2016 Medicare claims data, we identified patients with non-valvular AF who experienced an OAC-related ICH and survived at least 6 weeks after the ICH (n = 1502). The primary outcomes included the composite of ischemic stroke and transient ischemic attack (TIA), thromboembolism (TE), a composite of ischemic stroke/TIA and TE, recurrent ICH, and all-cause mortality. We constructed Cox proportional hazard models to evaluate the association between post-ICH OAC resumption, which was measured in a time-dependent manner, and the risk of primary outcomes, while controlling for a comprehensive list of covariates. Results: Among patients who survived an ICH, 69% reinitiated OAC within 6 weeks of the event, and among those who resumed OAC, 83% restarted warfarin. There was no significant difference in the risk of ischemic stroke/TIA (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.62–1.21), TE (HR 0.85, 95% CI 0.55–1.32), and ischemic stroke/TIA/TE (HR 0.81, 95% CI 0.61–1.07) between post-ICH OAC use and non-use. Post-ICH OAC use was associated with a lower risk of recurrent ICH (HR 0.62, 95% CI 0.41–0.95) and all-cause mortality (HR 0.48, 95% CI 0.37–0.62) compared with non-OAC use. Conclusions: In AF patients who survived an ICH, restarting OAC was not associated with a greater risk of recurrent ICH. Evidence from randomized controlled studies is needed to further clarify the clinical benefit of restarting OAC in this high-risk population. Further evaluation of which individuals benefit from restarting OAC is also needed to provide more clinical guidance. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to compare the risk of stroke in atrial fibrillation (AF) with adherent use of oral anticoagulation (OAC), non-adherent use, and non-use of OAC. Methods: Using 2013–2016 Medicare claims data, we identified patients newly diagnosed with AF in 2014–2015 and collected prescriptions filled for OAC in the 12 months after AF diagnosis (n = 39,272). We categorized participants each day into three time-dependent exposures: adherent use (≥ 80% of the previous 30 days covered with OAC), non-adherent use (0–80% covered with OAC), and non-use (0%). We constructed Cox proportional hazards models to estimate the association between time-dependent exposures and time to stroke, adjusting for demographics and clinical characteristics. Results: The sample included 39,272 patients. Study participants spent 35.0% of the follow-up period in the adherent use exposure category, 10.9% in the non-adherent category, and 54.0% in the non-use category. OAC adherent use [hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.52–0.74] and non-adherent use (HR 0.74; 95% CI 0.57–0.95) were associated with lower hazards of stroke than non-use. Adherent use of DOAC (HR 0.54; 95% CI 0.42–0.69) and warfarin (HR 0.70; 95% CI 0.56–0.89) was associated with lower risk of stroke than non-use, but the risk of stroke did not statistically differ between DOAC and warfarin adherent use (HR 0.77; 95% CI 0.56–1.04). Discussion: Although adherence to OAC reduces stroke risk by nearly 40%, newly diagnosed AF patients in Medicare adhere to OAC on average only one third of the first year after AF diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: It remains unknown whether the comparative effectiveness of direct oral anticoagulants (DOACs) and warfarin differs between patients with and without a history of stroke or transient ischemic attack (TIA). Hypothesis: We hypothesized that the comparative effectiveness of DOACs and warfarin differs between patients with and without a history of stroke or TIA. Methods: Using 2012-2014 Medicare Part D data, we identified patients newly diagnosed with atrial fibrillation in 2013-2014 who initiated apixaban(n=2358), dabigatran(n=1415), rivaroxaban (n=5139), or warfarin (n=12,352). We categorized them according to their history of stroke or TIA. Primary outcomes included the risk of ischemic stroke and of bleeding. We constructed Cox proportional hazard models that included indicator variables for treatment groups, a history of stroke or TIA, and the interaction between them, and controlled for demographics and clinical characteristics. Results: DOACs were generally more effective than warfarin; but the superiority of dabigatran was more pronounced in patients with a history of stroke or TIA: the hazard ratio (HR) for stroke with dabigatran vs. warfarin was 0.64(95%CI 0.48-0.85) for patients with history of stroke or TIA, 0.94(95%CI 0.75-1.16) for patients with no history of stroke or TIA (p-value for interaction=0.034). Although there was no difference in the risk of stroke between apixaban and dabigatran (HR 0.94;95%CI 0.71-1.24) or between apixaban and rivaroxaban (HR 1.01;95%CI, 0.81-1.27) for patients with no history of stroke or TIA, the risk of stroke was lower with dabigatran (HR 0.64;95%CI 0.48-0.85) and with rivaroxaban (HR 0.70;95%CI 0.56-0.87)[IH1] in patients with a history of stroke or TIA, compared to apixaban (p-value for both interactions<0.05). The comparative safety of DOACs and warfarin did not differ between patients with and without a history of stroke or TIA. Conclusion: The comparative effectiveness of DOACs differs between patients with and without a history of stroke or TIA; specifically, apixaban is less effective in patients with a history of stroke or TIA. Our results reinforce the need to tailor anticoagulation to patient characteristics and warrant the investigation of the underlying mechanisms for these differences. [ABSTRACT FROM AUTHOR]