Non-persistence to Oral Anticoagulation Treatment in Patients with Non-valvular Atrial Fibrillation in the USA.

BACKGROUND: Studies have shown that patients with non-valvular atrial fibrillation (NVAF) who discontinue oral anticoagulants (OACs) are at higher risk of complications such as stroke. OBJECTIVE: This analysis compared the risk of non-persistence with OACs among patients with NVAF. METHODS: Adult patients with NVAF who initiated apixaban, dabigatran, rivaroxaban, or warfarin were identified using 01JAN2013-30JUN2019 data from Centers for Medicare and Medicaid Services and four US commercial claims databases. Non-persistence was defined as discontinuation (no evidence of index OAC use for ≥ 60 days from the last days' supply) or switch to another OAC. Kaplan-Meier curves were generated to illustrate time to non-persistence along with cumulative incidences of non-persistence. Baseline and time-varying covariates were evaluated, and adjusted Cox proportional hazards models were used to evaluate non-persistence risk. RESULTS: In total, 363,823 patients receiving apixaban, 57,121 receiving dabigatran, 282,831 receiving rivaroxaban, and 317,337 receiving warfarin were included. Of these, 47-72% discontinued/switched OAC therapy within an average 9-month follow-up. Apixaban was associated with a lower risk of non-persistence than were dabigatran (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.61-0.62), rivaroxaban (HR 0.76; 95% CI 0.75-0.76), and warfarin (HR 0.74; 95% CI 0.74-0.75). Dabigatran was associated with a higher risk of non-persistence than were warfarin (HR 1.21; 95% CI 1.19-1.22) and rivaroxaban (HR 1.23; 95% CI 1.22-1.25), and rivaroxaban was associated with a lower risk of non-persistence than was warfarin (HR 0.98; 95% CI 0.97-0.98). Clinical events (stroke/systemic embolism and major bleeding [MB]) during follow-up were predictors of non-persistence (stroke HR 1.57; 95% CI 1.53-1.61; MB HR 2.96; 95% CI 2.92-3.00). CONCLUSION: In over one million patients with NVAF, our results suggest differences in anticoagulation treatment persistence across OAC agents, even after accounting for clinical events after OAC initiation. It is important for clinicians and patients to take these differences into consideration, especially as non-persistence to OAC therapy is associated with thromboembolic complications.

Oral Anticoagulants for Nonvalvular Atrial Fibrillation in Patients With High Risk of Gastrointestinal Bleeding.

Importance: Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastrointestinal (GI) bleeding due to conditions including older age; stage III to V chronic kidney disease (CKD); HAS-BLED (hypertension, kidney or liver disease, stroke history, prior bleeding, unstable international normalized ratio, age >65, drug or alcohol use) score of 3 or greater; corticosteroid, antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) use; or GI conditions. Objective: To compare the risk of stroke and/or systemic embolism (SE) and major bleeding (MB) among patients with NVAF and high risk of GI bleeding who received non-vitamin K antagonist oral anticoagulants (NOACs) vs those who received warfarin. Design, Setting, and Participants: This retrospective cohort study included patients with NVAF who were 75 years and older; had stage III to V CKD; had an HAS-BLED score of 3 or greater; used corticosteroids, antiplatelets, or NSAIDs; or had GI conditions. Data were collected from the Centers for Medicare & Medicaid Services and 4 commercial insurance databases between January 1, 2012, and September 30, 2015. Data analysis was conducted from January 2012 to September 2015. Exposures: New prescription for apixaban, dabigatran, rivaroxaban, or warfarin between January 1, 2013, and September 30, 2015 (identification period). Main Outcomes and Measures: Six propensity score-matched cohorts were created to compare between study drugs. For the primary objective, Cox models were used to estimate stroke and/or SE and MB hazard ratios (HRs). Results: A total of 381 054 patients (187 489 [49.2%] women) with NVAF and at least 1 high-risk GI bleeding factor were identified (HAS-BLED score ≥3: 284 527 [74.7%]; aged ≥75 years: 252 835 [66.4%]; corticosteroid, antiplatelet, or NSAID therapy: 107 675 [28.3%]; prior GI bleeding conditions: 74 818 [19.6%]; and stage III-V CKD: 56 892 [14.9%]). All NOACs were associated with a lower risk of stroke and/or SE vs warfarin (apixaban: HR, 0.60; 95% CI, 0.52-0.68; dabigatran: HR, 0.75; 95% CI, 0.64-0.88; rivaroxaban: HR, 0.79; 95% CI, 0.73-0.86). Compared with warfarin, apixaban and dabigatran were associated with a lower risk of MB (apixaban: HR, 0.59; 95% CI, 0.56-0.63; dabigatran: HR, 0.78; 95% CI, 0.70-0.86), while rivaroxaban was associated with a higher risk (HR, 1.11; 95% CI, 1.05-1.16). Conclusions and Relevance: In this study of patients with NVAF and high risk of GI bleed, NOACs were associated with lower rates of stroke and/or SE, but NOACs had varying risks of MB compared with warfarin. These results may help inform treatment options in this patient population.

Clinical and Economic Outcomes Among Nonvalvular Atrial Fibrillation Patients With Coronary Artery Disease and/or Peripheral Artery Disease.

To address literature gaps on treatment with real-world evidence, this study compared effectiveness, safety, and cost outcomes in NVAF patients with coronary or peripheral artery disease (CAD, PAD) prescribed apixaban versus other oral anticoagulants. NVAF patients aged ≥65 years co-diagnosed with CAD/PAD initiating warfarin, apixaban, dabigatran, or rivaroxaban were selected from the US Medicare population (January 1, 2013 to September 30, 2015). Propensity score matching was used to match apixaban versus warfarin, dabigatran, and rivaroxaban cohorts. Cox models were used to evaluate the risk of stroke/systemic embolism (SE), major bleeding (MB), all-cause mortality, and a composite of stroke/myocardial infarction/all-cause mortality. Generalized linear and two-part models were used to compare stroke/SE, MB, and all-cause costs between cohorts. A total of 33,269 warfarin-apixaban, 9,335 dabigatran-apixaban, and 33,633 rivaroxaban-apixaban pairs were identified after matching. Compared with apixaban, stroke/SE risk was higher in warfarin (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.61 to 2.31), dabigatran (HR: 1.69; 95% CI: 1.18 to 2.43), and rivaroxaban (HR: 1.24; 95% CI: 1.01 to 1.51) patients. MB risk was higher in warfarin (HR: 1.67; 95% CI: 1.52 to 1.83), dabigatran (HR: 1.37; 95% CI: 1.13 to 1.68), and rivaroxaban (HR: 1.87; 95% CI: 1.71 to 2.05) patients vs apixaban. Stroke/SE- and MB-related medical costs per-patient per-month were higher in warfarin, dabigatran, and rivaroxaban patients versus apixaban. Total all-cause health care costs were higher in warfarin and rivaroxaban patients compared with apixaban patients. In conclusion, compared with apixaban, patients on dabigatran, rivaroxaban, or warfarin had a higher risk of stroke/SE, MB, and event-related costs.

Healthcare resource utilization and expenditures among newly-diagnosed elderly non-valvular atrial fibrillation patients initiating oral anticoagulants.

Aims: Non-valvular atrial fibrillation (NVAF) prevalence increases with age. Hence, evaluating the economic burden among older-aged patients is vital. This study aimed to compare healthcare resource utilization (HRU) and costs among newly-diagnosed older-aged NVAF patients treated with warfarin, rivaroxaban, or apixaban vs. dabigatran.Materials and Methods: Newly-diagnosed older-aged (aged ≥65 years) NVAF patients initiating dabigatran, warfarin, rivaroxaban, or apixaban (first prescription date = index date) from 01JAN2010-31DEC2015 and with continuous enrollment for ≥12 months pre-index date were included from 100% Medicare database. Patient data were assessed until drug discontinuation/switch/dose change/death/disenrollment/study end (up to 12 months). Dabigatran initiators were 1:1 propensity score-matched (PSM) with warfarin, rivaroxaban, or apixaban initiators. Generalized linear models were used to compare all-cause HRU and costs per-patient-per-month (PPPM) between the matched cohorts.Results: After PSM with dabigatran, 70,531 warfarin, 51,673 rivaroxaban, and 25,209 apixaban patients were identified. Dabigatran patients had significantly fewer generalized-linear-model-adjusted PPPM hospitalizations (0.114 vs. 0.123; 0.111 vs. 0.121), and outpatient visits (2.864 vs. 4.201; 2.839 vs. 2.949) than warfarin and rivaroxaban patients, respectively, but had significantly more PPPM hospitalizations (0.103 vs. 0.090) and outpatient visits (2.780 vs. 2.673) than apixaban patients (all p < .0001). Dabigatran patients incurred significantly lower adjusted total PPPM costs ($3,309 vs. $3,362; $3,285 vs. $3,474) than warfarin and rivaroxaban patients, respectively (all p < .01) but higher total PPPM costs ($3,192 vs. $2,986) than apixaban patients (all p < .0001).Limitations: This study is subject to the inherent limitations of any claims dataset, including potential bias from coding errors and identification of medical conditions using diagnosis codes as opposed to clinical evidence. Medications filled over-the-counter or provided as samples by the physician are never captured in claims data.Conclusions: Newly-diagnosed older-aged NVAF patients initiating dabigatran incurred significantly lower adjusted all-cause HRU and costs than warfarin and rivaroxaban patients but higher adjusted HRU and costs than apixaban patients.

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.

Serotonin transporter gene polymorphism implicates reduced orbito-frontal cortex in obsessive-compulsive disorder.

Although a number of magnetic resonance imaging (MRI) and genetic studies have been performed on obsessive-compulsive disorder (OCD), only limited studies in which genetic and neuroanatomical variables are evaluated concurrently have been performed. Therefore, the aim of our present study is (to understand) better understanding how genetic variation in the promoter region of the 5-HTT gene (5-HTTLPR) is associated with key brain structures in OCD, orbito-frontal cortex (OFC), thalamus and anterior cingulate. 5-HTT genotypes (SS, SL, LL) were determined for 40 patients with OCD and the same number of healthy controls. MRI-derived volumes of the OFC, thalamus, and anterior cingulate were determined by reliable tracing techniques. Volumetric measurements were made with T1-weighted coronal MRI images, with 1.5-mm-thick slices, at 1.5T, and were done blindly. In comparison with controls, OCD patients demonstrated volumes reduction in OFC, increased volumes of thalamus and total white matter volumes, but no difference in total brain volume, total gray matter volumes and anterior cingulate volumes. No significant difference was observed in allelic frequencies between the patients and controls. The stronger effects of 5-HTT polymorphism on brain morphology in OCD than those in controls were determined in the both OFC and thalamus. On the other hand, for the OCD patients, ANCOVA revealed a significant main effect of genotype for both the OFC and thalamus and a significant genotype-by-side interaction for the OFC, demonstrating that the short variants had a smaller right OFC than the long variants. In conclusion, we found a significant genotype-diagnosis interaction effects on key brain structures, with a stronger effects of 5-HTT polymorphism in OFC and thalamus of OCD patients, whereas no morphological changes related to the polymorphism were found in normal individuals.