Health care resource utilization and costs associated with diagnosed medication overuse headache and potential acute medication overuse in individuals with migraine.

OBJECTIVE: Estimate health care resource utilization and costs associated with medication overuse headache and potential acute medication overuse. METHODS: A retrospective analysis was conducted with Clinformatics Data Mart data (1 January 2019-31 December 2019) that included continuously enrolled commercially insured adults with migraine (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] code G43.xxx). Medication overuse headache was defined as ≥1 inpatient or ≥2 outpatient claims with an ICD-10-CM code G44.41/40 (drug-induced headache). Potential acute medication overuse was defined as possessing sufficient medication for >10 mean treatment days/month for ergots, triptans, opioids, or combination analgesics or >15 mean cumulative days/month for simple prescription analgesics (e.g., acetaminophen, aspirin, other non-opioid analgesics) for >6 consecutive months. All-cause and migraine-related health care resource utilization and costs were compared after adjusting for demographic and clinical characteristics. RESULTS: Among 90,017 individuals with migraine, the frequency of medication overuse headache/potential acute medication overuse was 12.6% (diagnosed medication overuse headache: 0.6%; potential acute medication overuse: 12.1%). Adjusted all-cause total costs ($31,235 vs $21,486; difference: $9,749 [P < 0.001]) and adjusted migraine-related total costs ($9,770 vs $6,207; difference: $3,563 [P < 0.001]) were higher in the medication overuse headache/potential acute medication overuse group versus those without medication overuse headache/potential acute medication overuse. CONCLUSIONS: Individuals with diagnosed medication overuse headache/potential acute medication overuse had higher all-cause and migraine-related health care resource utilization and costs versus individuals without medication overuse headache/potential acute medication overuse, suggesting that improved migraine management is needed to reduce associated costs.

Functionality, satisfaction, and global impression of change with ubrogepant for the acute treatment of migraine in triptan insufficient responders: a post hoc analysis of the ACHIEVE I and ACHIEVE II randomized trials.

BACKGROUND: Triptans are the first-line option for the acute treatment of migraine attacks; however, triptans are contraindicated in people with certain underlying cardiovascular risk factors and are associated with inadequate efficacy or poor tolerability in some individuals. Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine. METHODS: This post hoc analysis of the phase 3 ACHIEVE trials examined the impact of ubrogepant on the Functional Disability Scale (FDS), satisfaction with medication, and Patient Global Impression of Change (PGIC) in participants who were self-reported triptan insufficient responders (TIRs), defined as those who are unable to take triptans due to contraindications, tolerability issues, or insufficient efficacy. Responder definitions for the FDS, satisfaction measures, and PGIC were based on qualitative interpretation of the respective response options for the pooled ubrogepant 50 mg and placebo groups. RESULTS: In the pooled analysis population (n = 1799), 451 (25%) participants were TIRs, with most (80%) reporting insufficient efficacy with triptan use. A significantly higher proportion of TIRs treated with ubrogepant vs placebo reported being able to function normally from 2 to 8 h post dose (P < 0.05). Notably, significance was demonstrated at the time of the primary outcome assessments (2 h post dose), where rates of normal function were 38% for ubrogepant vs 29% for placebo (P = 0.048). A greater proportion of TIRs in the ubrogepant arm vs the placebo arm were satisfied with treatment at 2 (33% vs 21%, P = 0.006) and 24 h (58% vs 28%, P < 0.001) and indicated that their migraine improved at 2 h vs placebo (30% vs 18%, P = 0.006). Results were generally similar in the insufficient efficacy subpopulation of TIRs as in the overall TIRs group. Ubrogepant was safe and well tolerated in TIRs, with no new safety signals identified. CONCLUSIONS: In people with migraine who are TIRs, individuals treated with ubrogepant had favorable 2-h outcomes, as measured by the FDS, satisfaction with medication, and PGIC, compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02828020 (ACHIEVE I), registered July 11, 2016; NCT02867709 (ACHIEVE II), registered August 16, 2016.

Geographic variation in the use of triptans and opioids for the acute treatment of migraine attacks.

OBJECTIVE: To assess the geographic variations in triptan and opioid prescribing patterns for patients with migraine. BACKGROUND: Numerous guidelines recommend triptans as the standard of care for migraine attacks, yet opioids are still widely used for migraine treatment. Variation in the use of opioids and triptans for the treatment of migraine by geographic location is not well known. METHODS: Using a US claims database, we conducted a retrospective cohort study of adults diagnosed with migraine between 2016 and 2018. We used a 12-month follow-up period to assess triptan and opioid utilization, stratified by the nine Census Bureau-designated divisions. To examine the geographic factors that affect triptan and opioid use among patients, we conducted two sets of multivariable analyses. First, we analyzed the odds of a patient being a triptan or opioid user in the follow-up period, defined as ≥1 triptan or opioid claim. We then analyzed the medication use rate among triptan or opioid users. RESULTS: Overall, we had a final study population of 113,921 patients. In the follow-up period, 52.9% (60,247/113,921) [range: 48.0%-56.3%] of patients were triptan users and 41.0% (46,708/113,921) [range: 28.9%-48.4%] of patients were opioid users with significant differences across census divisions (p < 0.001). Triptan users had a mean (SD) of 4.8 (4.7) triptan claims annually with no significant differences across divisions (p = 0.188). Opioid users had a mean (SD) of 5.4 (6.8) opioid claims annually with significant differences across divisions (p < 0.001). The observed variation in opioid use stemmed from the proportion of patients using opioids in each region and not from the number of opioid prescriptions per user. CONCLUSIONS: There was a significant geographic variation in the use of opioids and to a lesser degree the use of triptans. The widespread use of opioids and the large variation in use other than triptans as the standard of care suggest that improvements could be made in the acute treatment of migraine attacks.

Migraine Patients With Cardiovascular Disease and Contraindications: An Analysis of Real-World Claims Data.

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.

Comparison of healthcare resource utilization and costs among patients with migraine with potentially adequate and insufficient triptan response.

BACKGROUND: Triptans are the most commonly prescribed acute treatments for migraine; however, not all triptan users experience adequate response. Information on real-world resource use and costs associated with triptan insufficient response are limited. METHODS: A retrospective claims analysis using US commercial health plan data between 2012 and 2015 assessed healthcare resource use and costs in adults with a migraine diagnosis newly initiating triptans. Patients who either did not refill triptans but used other non-triptan medications or refilled triptans but also filled non-triptan medications over a 24-month follow-up period were designated as potential triptan insufficient responders. Patients who continued filling only triptans (i.e. triptan-only continuers) were designated as potential adequate responders. All-cause and migraine-related resource use and total (medical and pharmacy) costs over months 1-12 and months 13-24 were compared between triptan-only continuers and potential triptan insufficient responders. RESULTS: Among 10,509 new triptan users, 4371 (41%) were triptan-only continuers, 3102 (30%) were potential triptan insufficient responders, and 3036 (29%) did not refill their index triptan or fill non-triptan medications over 24 months' follow-up. Opioids were the most commonly used non-triptan treatment (68%) among potential triptan insufficient responders over 24 months of follow-up. Adjusted mean all-cause and migraine-related total costs were $5449 and $2905 higher, respectively, among potential triptan insufficient responders versus triptan-only continuers over the first 12 months. CONCLUSIONS: In a US commercial health plan, almost one-third of new triptan users were potential triptan insufficient responders and the majority filled opioid prescriptions. Potential triptan insufficient responder patients had significantly higher all-cause and migraine-related healthcare utilization and costs than triptan-only continuers.

Acute treatment patterns in patients with migraine newly initiating a triptan.

BACKGROUND: Triptans are the most commonly used acute treatment for migraine. This study evaluated real-world treatment patterns following an initial triptan prescription to understand refill rates and use of non-triptan medications for the acute treatment of migraine. METHODS: Commercially-insured adult patients over 18 years of age with a triptan prescription between 1/1/2013 to 31/12/2013 were identified from the Optum Clinformatics™ Data Mart database, with date of the first triptan fill designated as index date. Inclusion was limited to those with no fills for a triptan in the 12 months prior to index date (i.e. new users or initiators of triptans) and continuous enrollment in the 12 months pre- and 24 months post-index date. Fills for index triptan, non-index triptan, and other acute treatments for migraine were assessed for up to 24 months post-index. RESULTS: Among 10,509 patients, 50.8% did not refill the initial triptan within 12 months and 43.6% did not refill within 24 months. In the 12 months post-index, 90.5% of patients used only one type of triptan, 8.4% used two different triptans, and 1.0% used three or more triptans. Among patients with and without a triptan refill, use of opioids (39% vs. 42%), non-steroidal anti-inflammatory drugs (22% vs. 22%), and butalbital-containing products (9% vs. 10%) were similar. CONCLUSION: More than half of those who newly initiated a triptan did not refill their initial prescription, and less than 1 in 10 used two or more triptans within 12 months. High rates of non-triptan acute medication use were found over 12 and 24 months of follow-up, most commonly opioids.

Ubrogepant, an Acute Treatment for Migraine, Improved Patient-Reported Functional Disability and Satisfaction in 2 Single-Attack Phase 3 Randomized Trials, ACHIEVE I and II.

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 (ACHIEVE I: 50 mg, 34.4% [103/299], P = .0006 vs placebo; 100 mg, 34.3% [102/297], P = .0009 vs placebo; placebo, 22.0% [69/313]; ACHIEVE II: 25 mg, 34.1% [124/364], P < .0001 vs placebo; 50 mg, 33.4% [131/392], P = .0002 vs placebo; placebo, 20.7% [78/376]; pooled 50 mg, 33.9% [234/691], vs pooled placebo, 21.3% [147/689]; P < .0001). CONCLUSIONS: A significantly higher proportion of participants treated with ubrogepant were able to function normally, were satisfied with the study medication, and reported clinically meaningful improvement compared with those receiving placebo. The results reinforce the potential benefits of ubrogepant on patient-centered outcomes in the acute treatment of migraine.

Development of a claims-based algorithm to identify potentially undiagnosed chronic migraine patients.

OBJECTIVE: To develop a claims-based algorithm to identify undiagnosed chronic migraine among patients enrolled in a healthcare system. METHODS: An observational study using claims and patient survey data was conducted in a large medical group. Eligible patients had an International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) migraine diagnosis, without a chronic migraine diagnosis, in the 12 months before screening and did not have a migraine-related onabotulinumtoxinA claim in the 12 months before enrollment. Trained clinicians administered a semi-structured diagnostic interview, which served as the gold standard to diagnose chronic migraine, to enrolled patients. Potential claims-based predictors of chronic migraine that differentiated semi-structured diagnostic interview-positive (chronic migraine) and semi-structured diagnostic interview-negative (non-chronic migraine) patients were identified in bivariate analyses for inclusion in a logistic regression model. RESULTS: The final sample included 108 patients (chronic migraine = 64; non-chronic migraine = 44). Four significant predictors for chronic migraine were identified using claims in the 12 months before enrollment: ≥15 versus <15 claims for acute treatment of migraine, including opioids (odds ratio = 5.87 [95% confidence interval: 1.34-25.63]); ≥24 versus <24 healthcare visits (odds ratio = 2.80 [confidence interval: 1.08-7.25]); female versus male sex (odds ratio = 9.17 [confidence interval: 1.26-66.50); claims for ≥2 versus 0 unique migraine preventive classes (odds ratio = 4.39 [confidence interval: 1.19-16.22]). Model sensitivity was 78.1%; specificity was 72.7%. CONCLUSIONS: The claims-based algorithm identified undiagnosed chronic migraine with sufficient sensitivity and specificity to have potential utility as a chronic migraine case-finding tool using health claims data. Research to further validate the algorithm is recommended.

A Multicenter, Prospective, Observational Study to Determine Predictive Factors for Multidrug-Resistant Pneumonia in Critically Ill Adults: The DEFINE Study.

OBJECTIVE: This study was conducted to describe the prevalence, epidemiology, and clinical outcomes of multidrug-resistant (MDR) organism (MDRO) pneumonia in critically ill patients. METHODS: A multicenter, prospective, observational study of patients admitted to 60 intensive care units (ICUs), from 34 hospitals, in the United States from November to December 2016. Adults (> 18 yrs) receiving antimicrobial therapy at least 5 days for pneumonia were included. Patients were classified into two categories, with or without MDRO, and subcategorized by pneumonia type. MEASUREMENTS AND MAIN RESULTS: Demographics, medication histories, and health care exposure were collected during ICU admission and compared using t test and chi-square tests. Multivariate logistic regression was used to determine predictive factors for MDRO pneumonia and hospital mortality. Of 652 patients, 92 patients (14.1%) developed MDR pneumonia. Predictors of MDRO pneumonia were acid suppression therapy within the previous 90 days (odds ratio [OR] 1.88 [1.14-3.09]; p=0.013), mechanical ventilation (OR 1.96 [1.14-3.35]; p<0.001), and history of MDRO infection (OR 4.74 [2.21-10.18]; p<0.001). Appropriate initial antimicrobial selection occurred in 58 patients (63%) with MDRO pneumonia compared to 464 patients (82.7%) in patients without MDRO pneumonia (p<0.001). MDRO pneumonia was not associated with hospital mortality (18.5% vs 17.6%, p=0.087). CONCLUSIONS: In a broad cohort of critically ill patients, MDRO pneumonia is infrequent, and associated with factors describing the intensity of health care provided. Presence of MDRO pneumonia is not associated with hospital mortality. Further study is needed to clarify risk factors for multidrug-resistant pneumonia in critically ill patients.

Long term outcomes of new generation drug eluting stents versus coronary artery bypass grafting for multivessel and/or left main coronary artery disease. A Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: Most data guiding revascularization of multivessel disease (MVD) and/or left main disease (LMD) favor coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI). However, those data are based on trials comparing CABG to bare metal stents (BMS) or old generation drug eluting stents (OG-DES). Hence, it is essential to outcomes of CABG to those of new generation drug eluting stents (NG-DES). METHODS: We searched PUBMED and Cochrane database for trials evaluating revascularization of MVD and/or LMD with CABG and/or PCI. A Bayesian network meta-analysis was performed to calculate odds ratios (OR) and 95% credible intervals (CrI). Primary outcome was major adverse cardiovascular events (MACE) at 3-5 years. Secondary outcomes were mortality, cerebrovascular accidents (CVA), myocardial infarction (MI) and repeat revascularization. RESULTS: We included 10 trials with a total of 9287 patients. CABG was associated with lower MACE when compared to BMS or OG-DES. However, MACE was not significantly different between CABG and NG-DES (OR 0.79, CrI 0.45-1.40). Moreover, there were no significant differences between CABG and NG-DES in mortality (OR 0.78, CrI 0.45-1.37), CVA (OR 0.93 CrI 0.35-2.2) or MI (OR 0.6, CrI 0.17-2.0). On the other hand, CABG was associated with lower repeat revascularization (OR 0.55, CrI 0.36-0.84). CONCLUSIONS: Our study suggests that NG-DES is an acceptable alternative to CABG in patients with MVD and/or LMD. However, repeat revascularization remains to be lower with CABG than with PCI.

Comparative Effectiveness of Intra-Articular Hyaluronic Acid and Corticosteroid Injections on the Time to Surgical Knee Procedures.

BACKGROUND: Use of intra-articular hyaluronic acid (HA) injections to manage knee osteoarthritis (OA) remains controversial because of weak and conflicting evidence. The objective was to evaluate the effectiveness of intra-articular HA injections for knee OA management. METHODS: A nested cohort of persons with knee OA seeing a specialist was created using a 10% random sample of LifeLink Plus claims (2010-2015) to compare the risk of composite (any) knee surgical interventions, total (TKA)/unicompartmental knee arthroplasty (UKA) and TKA only among HA users and 2 comparison groups: corticosteroid (CS) users and HA/CS nonusers. A high-dimensional propensity score (hdPS) was used to match HA users with CS users and with HA/CS nonusers on background covariates. The risk of surgical interventions among HA users relative to the comparison groups was assessed using Cox proportional hazard models. RESULTS: Among 13,849 patients, 797 were HA users, 5327 were CS users, and 7725 were HA/CS nonusers. After hdPS matching, the risk of composite surgical interventions did not differ between HA users and HA/CS nonusers (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.67-1.16) and CS users (HR, 0.89; 95% CI, 0.65-1.12). Seven of the 8 sensitivity analyses demonstrated no significant benefit among HA users compared to CS users and HA/CS nonusers. A sensitivity analysis that restricted the study cohort to those who ultimately have knee surgery showed a lower risk of surgery of HA (HR, 0.87; 95% CI, 0.79-0.95). CONCLUSION: There were no significant differences in the risk of surgical interventions among HA users compared to HA/CS nonusers and CS users after accounting for residual confounding using an hdPS.

Adherence to Rivaroxaban, Dabigatran, and Apixaban for Stroke Prevention for Newly Diagnosed and Treatment-Naive Atrial Fibrillation Patients: An Update Using 2013-2014 Data.

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. DISCLOSURES: This project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant number UL1TR000117. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors have nothing to disclose. Study concept and design were contributed by Brown and Shewale. Brown and Talbert collected the data, and data analysis was performed primarily by Brown, along with Shewale and Talbert. The manuscript was written primarily by Brown, along with Shewale, and revised by all the authors.

Comparison of Low-, Moderate-, and High-Molecular-Weight Hyaluronic Acid Injections in Delaying Time to Knee Surgery.

BACKGROUND: We compared the effectiveness of low-molecular-weight (MW) hyaluronic acid (HA) injections (LMWHA), moderate-MW HA injections (MMWHA), and high-MW HA injections (HMWHA) for prevention or delay of knee surgery in patients with knee osteoarthritis. METHODS: An observational cohort study using LifeLink Plus claims (2006-2015) was used. The primary outcome measure of the study included all surgical interventions of the knee. The secondary outcome measures were the following: (1) unicompartmental knee arthroplasty or total knee arthroplasty and (2) total knee arthroplasty only. A high-dimensional propensity score (hdPS) using 1:1 matching was used to adjust for confounding. The likelihood of each outcome was assessed using Cox proportional hazard models. RESULTS: A cohort of 30,417 incident HA users with knee osteoarthritis met our inclusion-exclusion criteria. There was no difference in the likelihood of composite surgical events between LMWHA users (hazard ratio, 0.939; 95% confidence interval, 0.870-1.013) and MMWHA users (hazard ratio, 1.032; 95% confidence interval, 0.952-1.119) when compared with HMWHA users in a matched hdPS analysis. However, a significantly lower likelihood for all outcome measures was demonstrated in LMWHA and MMWHA users compared with HMWHA users when hdPS was not used. CONCLUSION: There was no significant difference in the likelihood of surgical interventions between LMWHA, MMWHA, and HMWHA users after accounting for empirically derived confounders.

Adherence to Rivaroxaban, Dabigatran, and Apixaban for Stroke Prevention in Incident, Treatment-Naïve Nonvalvular Atrial Fibrillation.

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, CHA2 DS2-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 outcomes as well as quality assessment. DISCLOSURES: The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant number UL1TR000117. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Brown reports receiving a training fellowship from Human and Pfizer. Study concept and design were contributed by Brown and Shewale. Talbert took the lead in data collection, along with Brown, and data interpretation was primarily performed by Brown, along with Shewale. The manuscript was written primarily by Brown, along with Shewale, and revised by all the authors.

A Comparison of Oral Anticoagulant Use for Atrial Fibrillation in the Pre- and Post-DOAC Eras.

INTRODUCTION: Direct oral anticoagulants (DOACs) have seen rapid uptake for the prevention of stroke associated with non-valvular atrial fibrillation (NVAF). It is unclear whether use of DOACs represents direct therapeutic substitution over warfarin or if this coincides with an increase in overall treatment rates. This study sought to describe the difference in oral anticoagulant (OAC) use in the pre-DOAC and post-DOAC eras. METHODS: Incident cases of NVAF were identified from the Truven Marketscan database during the years 2005-2009 ('pre-DOAC') and 2013 ('post-DOAC'). Demographic and clinical characteristics were compared for the overall cohorts and among those who did and did not receive OAC in both time periods. OAC treatment was observed by stroke (CHA2DS2-VASc) and bleed risk (HAS-BLED) scores. Logistic regression was used to compare the individual characteristics associated with OAC use between the study periods. RESULTS: During the pre- and post-DOAC eras, 105,610 and 11,992 NVAF patients were identified. OAC treatment increased from 42.2 to 54.0 % (absolute change 11.8 %, relative change 28.0 %) from the pre- to post-DOAC periods without meaningful differences between the populations. Larger relative increases in OAC treatment were observed for those at high risk of stroke (33.9 % increase) and for those with moderate (30.4 % increase) to high risk (28.6 % increase) of bleed. Other than time period of diagnosis, no patient characteristics differed between those treated with OACs in the pre and post periods. CONCLUSIONS: There has been an overall increase in OAC use in the NVAF population, attributable to both favorable randomized trial results and aggressive marketing of DOACs in the USA.

Cost-Effectiveness of Oral Anticoagulants for Ischemic Stroke Prophylaxis Among Nonvalvular Atrial Fibrillation Patients.

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 (CHADS2 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 CHADS2 ≥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 (CHADS2≥3), dabigatran was the most cost-effective treatment option.

Net Clinical Benefits of Guidelines and Decision Tool Recommendations for Oral Anticoagulant Use among Patients with Atrial Fibrillation.

BACKGROUND: The 2012 American College of Chest Physicians' Evidence-Based Clinical Practice (CHEST), the 2012 European Society of Cardiology, and the 2014 American Heart Association guidelines and published decision tools by LaHaye and Casciano offer oral anticoagulant (OAC) recommendations for patients with atrial fibrillation (AF). The aim of our study was to compare the net clinical benefit (NCB) of OAC prescribing that was concordant with these decision aids. METHODS: A cohort study of the 2001-2013 LifeLink claims data was used. NCB in concordance with each decision aid was defined as adverse events (thromboembolic and major bleed events) prevented per 10,000 person-years. Cox proportional hazard models were used to assess the relative risk of AF adverse events associated in concordance with each decision aid adjusted for potential confounders. FINDINGS: The study included 15,129 patients with AF, contributing 33,512 person-years. The NCB of the CHEST guidelines was the highest (NCB = 30.07; 95% confidence interval [CI] = 28.66, 31.49) and the European Society of Cardiology guidelines the lowest (NCB = 7.38; 95% CI = 5.97, 8.80). Significant unadjusted decreases in the risk of AF adverse events associated with concordant OAC use/nonuse were found for the CHEST guidelines (hazard ratio [HR] = .825; 95% CI = .695, .979), Casciano tool (HR = .838; 95% CI = .706, .995), and LaHaye tool (HR = .841; 95% CI = .709, .999); however, none were significant after multivariate adjustment. CONCLUSION: Concordant OAC use with any of the decision aids except for the aggressive LaHaye tool led to a positive NCB. The decision aids based on the CHA2DS2-VASc algorithm did not consistently improve the NCB compared to CHADS2-based aids. Recommending OAC use when CHA2DS2-VASc score = 1 resulted in a lower NCB when all other factors guiding recommendations were held constant.

Mental health status of varenicline and bupropion users during a quit attempt compared to current smokers, other quitters, and non-smokers.

BACKGROUND: Varenicline and bupropion are commonly prescribed non-nicotine containing smoking cessation agents. Post-marketing reports suggest an increased incidence of psychiatric disturbances associated with varenicline and bupropion. However, pre-existing psychiatric disorders may confound the association between these smoking cessation agents and psychiatric disturbances. We compared the mental health status of individuals using varenicline or bupropion to that of people quitting without medication, current smokers, and non-smokers while controlling for pre-existing conditions. METHODS: A cross-sectional design was used. Data were from 2006-2011 Medical Expenditure Panel Survey. Mental health status was assessed using the mental component summary (MCS) from the 12-item Short Form survey (SF-12v2), 2-item Patient Health Questionnaire (PHQ-2), and Kessler 6 Scale (K6). Differences in MCS score were compared using linear regression. Logistic regressions were used to compare positive screenings for depression using PHQ-2 and for psychological distress using K6. RESULTS: Of 578 use episodes, 453 (78.38%) were bupropion and 125 (21.62%) were varenicline. After adjusting for potential confounders, mental health status of varenicline users was not different from current smokers or people who quit smoking without medication, but worse than non-smokers; bupropion was strongly associated with lower mental health status relative to all groups across all three measures. CONCLUSION: Varenicline was not associated with worse mental health compared to smokers or those who quit without medication, after adjusting for pre-existing psychiatric disorders. Bupropion was associated with worse mental health status than smokers, former smokers who quit without medication, and nonsmokers, even after adjusting for pre-existing psychiatric disorders.