Effectiveness and safety of direct oral anticoagulants compared to warfarin in treatment naïve non-valvular atrial fibrillation patients in the US Department of defense population.

BACKGROUND: Clinical trials have demonstrated that direct oral anticoagulants (DOACs) are at least non-inferior to warfarin in reducing the risk of stroke/systemic embolism (SE) among patients with non-valvular atrial fibrillation (NVAF), but the comparative risk of major bleeding varies between DOACs and warfarin. Using US Department of Defense (DOD) data, this study compared the risk of stroke/SE and major bleeding for DOACs relative to warfarin. METHODS: Adult patients with ≥1 pharmacy claim for apixaban, dabigatran, rivaroxaban, or warfarin from 01 Jan 2013-30 Sep 2015 were selected. Patients were required to have ≥1 medical claim for atrial fibrillation during the 12-month baseline period. Patients with a warfarin or DOAC claim during the 12-month baseline period were excluded. Each DOAC cohort was matched to the warfarin cohort using propensity score matching (PSM). Cox proportional hazards models were conducted to evaluate the risk of stroke/SE and major bleeding of each DOAC vs warfarin. RESULTS: Of 41,001 identified patients, there were 3691 dabigatran-warfarin, 8226 rivaroxaban-warfarin, and 7607 apixaban-warfarin matched patient pairs. Apixaban was the only DOAC found to be associated with a significantly lower risk of stroke/SE (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.39, 0.77; p < 0.001) and major bleeding (HR: 0.65; 95% CI: 0.53, 0.80; p < 0.001) compared to warfarin. Dabigatran and rivaroxaban initiation were associated with similar risk of stroke/SE (dabigatran: HR: 0.68; 95% CI: 0.43, 1.07; p = 0.096; rivaroxaban: HR: 0.83; 95% CI: 0.64, 1.09; p = 0.187) and major bleeding (dabigatran: HR: 1.05; 95% CI: 0.79, 1.40; p = 0.730; rivaroxaban: HR: 1.07; 95% CI: 0.91, 1.27; p = 0.423) compared to warfarin. CONCLUSION: Among NVAF patients in the US DOD population, apixaban was associated with significantly lower risk of stroke/SE and major bleeding compared to warfarin. Dabigatran and rivaroxaban were associated with similar risk of stroke/SE and major bleeding compared to warfarin.

Comparative clinical outcomes between direct oral anticoagulants and warfarin among elderly patients with non-valvular atrial fibrillation in the CMS medicare population.

Atrial fibrillation (AF) prevalence increases with age; > 80% of US adults with AF are aged ≥ 65 years. Compare the risk of stroke/systemic embolism (SE), major bleeding (MB), net clinical outcome (NCO), and major adverse cardiac events (MACE) among elderly non-valvular AF (NVAF) Medicare patients prescribed direct oral anticoagulants (DOACs) VS warfarin. NVAF patients aged ≥ 65 years who initiated DOACs (apixaban, dabigatran, and rivaroxaban) or warfarin were selected from 01JAN2013-31DEC2015 in CMS Medicare data. Propensity score matching was used to balance DOAC and warfarin cohorts. Cox proportional hazards models estimated the risk of stroke/SE, MB, NCO, and MACE. 37,525 apixaban-warfarin, 18,131 dabigatran-warfarin, and 55,359 rivaroxaban-warfarin pairs were included. Compared to warfarin, apixaban (HR: 0.69; 95% CI 0.59-0.81) and rivaroxaban (HR: 0.82; 95% CI 0.73-0.91) had lower risk of stroke/SE, and dabigatran (HR: 0.88; 95% CI 0.72-1.07) had similar risk of stroke/SE. Apixaban (MB: HR: 0.61; 95% CI 0.57-0.67; NCO: HR: 0.64; 95% CI 0.60-0.69) and dabigatran (MB: HR: 0.79; 95% CI 0.71-0.89; NCO: HR: 0.84; 95% CI 0.76-0.93) had lower risk of MB and NCO, and rivaroxaban had higher risk of MB (HR: 1.08; 95% CI 1.02-1.14) and similar risk of NCO (HR: 1.04; 95% CI 0.99-1.09). Compared to warfarin, apixaban had a lower risk for stroke/SE, MB, and NCO; dabigatran had a lower risk of MB and NCO; and rivaroxaban had a lower risk of stroke/SE but higher risk of MB. All DOACs had lower risk of MACE compared to warfarin.

Comparison of Drug Switching and Discontinuation Rates in Patients with Nonvalvular Atrial Fibrillation Treated with Direct Oral Anticoagulants in the United States.

INTRODUCTION: Continuous usage of direct oral anticoagulants (DOACs) among nonvalvular atrial fibrillation (NVAF) patients is essential to maintain stroke prevention. We examined switching and discontinuation rates for the three most frequently initiated DOACs in NVAF patients in the USA. METHODS: Patients who initiated apixaban, rivaroxaban, or dabigatran (index event/date) were identified from the Pharmetrics Plus claims database (Jan 1, 2013-Sep 30, 2016, includes patients with commercial and Medicare coverage) and grouped into cohorts by index DOAC. Patients were required to have a diagnosis of NVAF and continuous health plan enrollment for 12 months prior to the index date (baseline period) and at least 3 months during the follow-up period. Drug switching rates to any other DOAC or warfarin and index DOAC discontinuation rate were evaluated separately with descriptive statistics, Kaplan-Meier analysis, and multivariable Cox regression analysis. RESULTS: Of the NVAF study population (n = 41,864), 37% initiated apixaban (n = 15,352; mean age 62 years), 51% initiated rivaroxaban (n = 21,250; mean age 61 years), and 13% initiated dabigatran (n = 5262; mean age 61 years). During the follow-up period, the unadjusted drug switching rates of patients treated with apixaban, rivaroxaban, and dabigatran were 3.6%, 6.3%, and 11.1%, respectively (p < 0.001 across the three cohorts); while the index DOAC discontinuation rates were 52.8%, 60.3%, and 62.9%, respectively (p < 0.001). After we controlled for differences in patient characteristics, patients treated with rivaroxaban (HR 1.8; 95% CI 1.6-2.0; p < 0.001) and dabigatran (HR 3.4; 95% CI 3.0-3.8, p < 0.001) had a significantly greater likelihood for drug switching than patients treated with apixaban. Also, both rivaroxaban (HR 1.1; 95% CI 1.1-1.2, p < 0.001) and dabigatran (HR 1.3; 95% CI 1.2-1.3, p < 0.001) treated patients were more likely to discontinue treatment. CONCLUSION: In the real-world setting, patients with NVAF newly treated with apixaban were less likely to switch or discontinue treatment compared to patients treated with rivaroxaban or dabigatran. FUNDING: Pfizer and Bristol-Myers Squibb.

Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients.

Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285 292 patients were included in the 6 matched cohorts: 57 929 apixaban-warfarin, 26 838 dabigatran-warfarin, 83 007 rivaroxaban-warfarin, 27 096 apixaban-dabigatran, 62 619 apixaban-rivaroxaban, and 27 538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio [HR], 0.61; 95% CI, 0.54-0.69), dabigatran (HR, 0.80; 95% CI, 0.68-0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69-0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54-0.62) and dabigatran (HR, 0.73; 95% CI, 0.66-0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02-1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions- In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT03087487.

Major bleeding risk and healthcare economic outcomes of non-valvular atrial fibrillation patients newly-initiated with oral anticoagulant therapy in the real-world setting.

AIMS: This study compared the risk for major bleeding (MB) and healthcare economic outcomes of patients with non-valvular atrial fibrillation (NVAF) after initiating treatment with apixaban vs rivaroxaban, dabigatran, or warfarin. METHODS: NVAF patients who initiated apixaban, rivaroxaban, dabigatran, or warfarin were identified from the IMS Pharmetrics Plus database (January 1, 2013-September 30, 2015). Propensity score matching (PSM) was used to balance differences in patient characteristics between study cohorts: patients treated with apixaban vs rivaroxaban, apixaban vs dabigatran, and apixaban vs warfarin. Risk of hospitalization and healthcare costs (all-cause and MB-related) were compared between matched cohorts during the follow-up. RESULTS: During the follow-up, risks for all-cause (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.2-1.7) and MB-related (HR = 1.57, 95% CI = 1.0-2.4) hospitalizations were significantly greater for patients treated with rivaroxaban vs apixaban. Adjusted total all-cause healthcare costs were significantly lower for patients treated with apixaban vs rivaroxaban ($3,950 vs $4,333 per patient per month [PPPM], p = .002) and MB-related medical costs were not statistically significantly different ($100 vs $233 PPPM, p = .096). Risk for all-cause hospitalization (HR = 1.98, 95% CI = 1.6-2.4) was significantly greater for patients treated with dabigatran vs apixaban, although total all-cause healthcare costs were not statistically different. Risks for all-cause (HR = 2.22, 95% CI = 1.9-2.5) and MB-related (HR = 2.05, 95% CI = 1.4-3.0) hospitalizations were significantly greater for patients treated with warfarin vs apixaban. Total all-cause healthcare costs ($3,919 vs $4,177 PPPM, p = .025) and MB-related medical costs ($96 vs $212 PPPM, p = .026) were significantly lower for patients treated with apixaban vs warfarin. LIMITATIONS: This retrospective database analysis does not establish causation. CONCLUSIONS: In the real-world setting, compared with rivaroxaban and warfarin, apixaban is associated with reduced risk of hospitalization and lower healthcare costs. Compared with dabigatran, apixaban is associated with lower risk of hospitalizations.

Rates, factors, reasons, and economic impact associated with switching in rheumatoid arthritis patients newly initiated on biologic disease modifying anti-rheumatic drugs in an integrated healthcare system.

Objectives To identify how many RA patients newly-initiated on bDMARD therapy switch to another bDMARD during the first year of treatment; to evaluate the factors and reasons associated with bDMARD switching; and to compare the RA-related healthcare resource utilization (HCRU) and costs between switchers vs non-switchers during the post-index period. Methods A retrospective cohort study was conducted in RA patients using the Kaiser Permanente Southern California (KPSC) database with the study time period of January 1, 2007 to December 31, 2012. The index date was defined as the date of the first bDMARD prescription. Patients had to have continuous membership eligibility with drug benefit and no prior history of bDMARD during the 24 months prior to the index date. bDMARD switching was defined as a different bDMARD claim during post-index. A multivariable logistic regression model was used to evaluate factors associated with switchers vs non-switchers. Chart notes were reviewed to evaluate reasons for switching from index bDMARD. RA-related HCRU use and costs were evaluated using a generalized linear model (GLM) with gamma distribution and log link function. Results Two hundred and fifty-one patients (12%) switched from their index bDMARD to a different bDMARD during the post-index period. bDMARD switchers were more likely to be female, of Asian/Pacific race, younger than ≤65 years of age, overweight, CCI score ≤2, initiating etanercept or adalimumab, and have a commercial insurance plan compared to non-switchers. Reasons for switching were related mostly to lack or loss of efficacy (∼51%); bDMARD switchers had overall mean adjusted RA related total costs that were 25% higher (p = 0.04) compared to non-switchers. Conclusion It is important for RA patients to receive appropriate therapy and consider bDMARD with different mechanisms of action to decrease subsequent switching, and decrease overall RA related costs as shown in this study.