BACKGROUND Few studies have assessed adherence to non-vitamin K antagonist oral anticoagulants (NOACs), especially using contemporary data now that multiple NOACs are available. OBJECTIVE To compare adherence and treatment patterns among NOACs for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). METHODS Incident and treatment-naive NVAF patients were identified during 2013–2014 from a large claims database in this retrospective cohort study. Patients were included who initiated rivaroxaban, dabigatran, or apixaban within 30 days after diagnosis. Adherence to the index medication and adherence to any oral anticoagulant was assessed using the proportion of days covered (PDC) at 3, 6, and 9 months. The number of switches and gaps in therapy were also evaluated. Analyses were stratified by stroke risk scores, and a logistic regression model was used to control for factors that may predict high adherence. RESULTS Dabigatran had lower adherence (PDC = 0.76, 0.64, 0.57) compared with rivaroxaban (PDC = 0.83, 0.73, 0.66; P < 0.001) and apixaban (PDC = 0.82, 0.72, 0.66; P < 0.001) at 3, 6, and 9 months of follow-up and twice the number of switches to either other anticoagulants or antiplatelet therapy. Adherence was higher overall as stroke risk increased, and dabigatran had consistently lower adherence compared with the other NOACs. Multivariable logistic regression predicting PDC ≥ 0.80 showed rivaroxaban users with higher odds of high adherence compared with dabigatran or rivaroxaban across all time periods. Adjusted analyses showed that increasing age and comorbid hypertension and diabetes were associated with higher adherence. CONCLUSIONS In this real-world analysis of adherence to NOACs, rivaroxaban and apixaban had favorable unadjusted adherence profiles compared with dabigatran, while rivaroxaban users had higher odds of high adherence (PDC ≥ 0.80) among the NOACs in adjusted analyses. Clinicians and managed care organizations should consider the implications of lower adherence on clinical outcomes and quality assessment.

BACKGROUND Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used for prevention of stroke secondary to nonvalvular atrial fibrillation (NVAF). Increased use of NOACs is partially a result of simplified regimens compared with warfarin, which has been associated with poor adherence and persistence to therapy. Few studies have assessed adherence to NOACs, especially using contemporary data now that multiple NOACs are available. OBJECTIVE To evaluate adherence to NOACs in a cohort of newly diagnosed NVAF patients who are commercially insured. METHODS Incident, treatment-naïve NVAF patients were identified in 2013 from a large claims database. Patients were included who initiated rivaroxaban, dabigatran, or apixaban within 30 days after diagnosis. Subjects were required to have 12 months of pre-index information to assess demographic and clinical characteristics (comorbidities, CHA2DS2-VASc, and HAS-BLED scores). Adherence to the index medication and adherence to any oral anticoagulant was assessed using proportion of days covered (PDC) at 3, 6, and 9 months. The number of switches and gaps in therapy were also evaluated. Analyses were stratified by stroke risk scores, and a logistic regression model was used to control for factors that may predict high adherence (PDC ≥ 0.80). RESULTS A total of 3,455 rivaroxaban, 1,264 dabigatran, and 504 apixaban users were included with no major clinical or demographic differences between groups. At 3, 6, and 9 months of follow-up, dabigatran had lower adherence (PDC = 0.77, 0.67, and 0.62) compared with rivaroxaban (PDC = 0.84, 0.75, and 0.70; P < 0.001) and apixaban (PDC = 0.82, 0.75, and 0.71; P < 0.001), as well as nearly twice the number of switches to either other anticoagulants or antiplatelet therapy. At 9 months, 55.0% of rivaroxaban initiators had PDC ≥ 0.80, which was comparable with 56.8% for apixaban and significantly greater than 46.7% for dabigatran (P < 0.001). Adherence was higher overall as stroke risk increased and showed dabigatran had consistently lower adherence compared with the other NOACs. Overall adherence to any oral anticoagulants, allowing for switches to another NOAC or warfarin, was not dependent on the index medication (9-month PDC = 0.74, 0.71, and 0.74 for rivaroxaban, dabigatran, and apixaban initiators). Adjusted analyses showed that increasing age and comorbid hypertension and diabetes were associated with higher adherence. Compared with rivaroxaban, dabigatran initiators had nearly 30% lower odds of being adherent to their index medication, and no differences were observed between apixaban and rivaroxaban. At 9 months, there were no differences between NOACs for overall adherence to oral anticoagulants. CONCLUSIONS In this real-world analysis of adherence to NOACs, rivaroxaban and apixaban had favorable profiles compared with dabigatran, and rivaroxaban appeared to have higher overall adherence among the NOACs. Clinicians and managed care organizations should consider the implications of lower adherence on clinical outc...

Background and Purpose— The objective of the study is to compare the cost-effectiveness of oral anticoagulants among atrial fibrillation patients at an increased stroke risk. Methods— A Markov model was constructed to project the lifetime costs and quality-adjusted survival (QALYs) of oral anticoagulants using a private payer’s perspective. The distribution of stroke risk (CHADS 2 score: congestive heart failure, hypertension, advanced age, diabetes mellitus, stroke) and age of the modeled population was derived from a cohort of commercially insured patients with new-onset atrial fibrillation. Probabilities of treatment specific events were derived from published clinical trials. Event and downstream costs were determined from the cost of illness studies. Drug costs were obtained from 2015 National Average Drug Acquisition Cost data. Results— In the base case analysis, warfarin was the least costly ($46 241; 95% CI, 44 499–47 874) and apixaban had the highest QALYs (9.38; 95% CI, 9.24–9.48 QALYs). Apixaban was found to be a cost-effective strategy over warfarin (incremental cost-effectiveness ratio=$25 816) and dominated other anticoagulants. Probabilistic sensitivity analysis showed that apixaban had at least a 61% chance of being the most cost-effective strategy at willingness to pay value of $100 000 per QALY. Among patients with CHADS 2 ≥3, dabigatran was the dominant strategy. The model was sensitive to efficacy estimates of apixaban, dabigatran, and edoxaban and the cost of these drugs. Conclusions— All the newer oral anticoagulants compared were more effective than adjusted dosed warfarin. Our model showed that apixaban was the most effective anticoagulant in a general atrial fibrillation population and has an incremental cost-effectiveness ratio <$50 000/QALY. For those with higher stroke risk (CHADS 2 ≥3), dabigatran was the most cost-effective treatment option.

Objective To evaluate the efficacy of ubrogepant on patient‐reported functional disability, satisfaction with study medication, and global impression of change. Background Ubrogepant is a small‐molecule, oral calcitonin gene‐related peptide receptor antagonist indicated for the acute treatment of migraine. In 2 phase 3 trials (ACHIEVE I and II), ubrogepant demonstrated efficacy vs placebo on the 2 co‐primary endpoints of headache pain freedom and absence of the most bothersome migraine‐associated symptom at 2 hours post dose for the 50 and 100 mg doses. Patient‐reported outcomes, such as functional disability, satisfaction, and patient global impression of change, can provide additional evidence of the efficacy of an acute treatment for migraine on clinically meaningful and patient‐relevant outcomes. Methods ACHIEVE I and ACHIEVE II were multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group, single‐attack trials in adults (18‐75 years) with migraine. In ACHIEVE I, participants were randomized 1:1:1 to placebo or ubrogepant 50 or 100 mg; in ACHIEVE II, participants were randomized 1:1:1 to placebo or ubrogepant 25 or 50 mg to treat a migraine attack with moderate or severe headache pain. Participants rated ability to perform daily activities on the Functional Disability Scale, before dosing and at 1, 2, 4, and 8 hours after the initial dose; satisfaction with study medication at 2 and 24 hours; and impression of overall change in migraine on the Patient Global Impression of Change scale at 2 hours. In prespecified analyses for each trial, each outcome was compared between each ubrogepant dose group and the relevant placebo group. Data were pooled from the ubrogepant 50 mg and placebo groups of the 2 trials in a post hoc analysis. Results In ACHIEVE I, 559 participants were randomized to placebo, 556 to ubrogepant 50 mg, and 557 to ubrogepant 100 mg; in ACHIEVE II, 563 were randomized to placebo, 561 to ubrogepant 25 mg, and 562 to ubrogepant 50 mg. At 2 hours post dose, significantly higher proportions of ubrogepant‐treated participants vs placebo‐treated participants reported being able to function normally (ACHIEVE I: ubrogepant 50 mg, 40.6% [171/421], P = .0012 vs placebo; ubrogepant 100 mg, 42.9% [192/448], P < .0001 vs placebo; placebo, 29.8% [136/456]; ACHIEVE II: ubrogepant 25 mg, 42.6% [185/434], P = .0015 vs placebo; ubrogepant 50 mg, 40.5% [188/464], P = .0118 vs placebo; placebo, 34.2% [156/456]; pooled 50 mg, 40.6% [359/885], vs pooled placebo, 32.0% [292/912]; P < .0001), were satisfied/extremely satisfied with study medication (ACHIEVE I: 50 mg, 36.3% [147/405], P < .0001 vs placebo; 100 mg, 35.8% [149/416], P = .0002 vs placebo; placebo, 24.1% [104/432]; ACHIEVE II: 25 mg, 35.1% [141/402], P = .0018 vs placebo; 50 mg, 37.8% [163/431], P < .0001 vs placebo; placebo, 24.8% [106/427]; pooled ubrogepant 50 mg, 37.1% [310/836], vs pooled placebo, 24.5% [210/859]; P < .0001), and indicated that their migraine was much/very much better on the Patient Global Impression of Change scale (A...

Introduction: Triptans, the most commonly prescribed acute treatments for migraine attacks are, per FDA labeling, contraindicated in cardiovascular (CV) disease patients and have warnings and precautions for those with CV risk factors. Methods: Headache specialists, cardiologists, and health economics and outcomes researchers convened to identify diagnostic codes for: (1) CV diseases contraindicating triptans based on FDA labeling; (2) conditions comprising “other significant underlying CV disease”; and (3) CV risk factors included as warnings and precautions for triptans. A retrospective, cross-sectional analysis of commercially insured adult US migraine patients in the 2017 Optum® Clinformatics® Data Mart (CDM) and the 2017 IBM® Watson Health MarketScan® Commercial Claims database was used to estimate the proportion of migraine patients with CV contraindications and warnings and precautions to triptans. Results: Of the 56,662 migraine patients analyzed from Optum CDM, 13.5% had ≥1 CV disease as specified in triptan labeling and an additional 8.5% had ≥1 “other CV disease” judged by the panel to constitute a “significant underlying CV disease” (total: 22.0% migraine patients). Of 176 724 migraine patients analyzed from MarketScan, 12.2% had ≥1 CV disease as specified in the labeling and an additional 8.0% had ≥1 “other significant underlying CV disease” (total: 20.2% of migraine patients). An additional 25.4% and 25.1% of migraine patients had ≥2 CV risk factors in Optum CDM and MarketScan. In total, 47.4% and 45.3% of migraine patients in both databases had a CV disease specified as a contraindication, an “other CV disease” endorsed as significant, or ≥2 CV risk factors identified as warnings and precautions to triptans. Conclusions: Analyses of more than 230,000 people with migraine showed that ≥20% of commercially insured US migraine patients have a CV condition that specifically contraindicates triptan treatment, and an additional 25% have ≥2 CV risk factors identified as warnings and precautions to triptans.