Publications

PURPOSE: The findings from the observational studies comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) for atrial fibrillation (AF) and venous thromboembolism (VTE) are inconsistent. We conducted separate meta-analyses examining the efficacy/effectiveness and safety of NOACs versus VKAs by disease (AF vs VTE), study design (randomized controlled trials [RCTs] vs observational studies), and NOAC (dabigatran, rivaroxaban, apixaban, and edoxaban).

METHODS: The main data sources included PubMed/MEDLINE, EMBASE, Web of Science, CINAHL, and Scopus from January 1, 2005, to February 15, 2016. We searched for Phase III RCTs and observational studies comparing NOACs versus VKAs. The primary outcomes were stroke/systemic embolism (SE) for AF; recurrent VTE/fatal pulmonary embolism (PE) for VTE; and major bleeding for both conditions. Secondary outcomes included stroke and myocardial infarction (MI) for AF, recurrent deep vein thrombosis (DVT)/PE for VTE, and mortality, intracranial hemorrhage (ICH), and gastrointestinal bleeding for both conditions. Pooled hazard ratios (HRs) were reported by using inverse variance-weighted random effects models.

FINDINGS: A total of 13 RCTs and 27 observational studies (AF, n = 32; VTE, n = 8) were included. For AF, dabigatran and VKAs were comparable for stroke/SE risk in 1 RCT (HR, 0.77 [95% CI, 0.57-1.03]) and 6 observational studies (HR, 1.03 [95% CI, 0.83-1.27]). Rivaroxaban had a 20% decreased risk of stroke/SE in 3 RCTs (HR, 0.80 [95% CI, 0.67-0.95]) compared with VKA, but the effect was nonsignificant in 3 observational studies (HR, 0.78 [95% CI, 0.59-1.04]). Apixaban decreased stroke/systemic embolism risk (HR, 0.79 [95% CI, 0.66-0.95]) compared with VKA in 1 RCT, but edoxaban was comparable to VKA (HR, 0.99 [95% CI, 0.77-1.28]) in 1 RCT (no observational studies available for apixaban/edoxaban). Dabigatran, apixaban, and edoxaban decreased the risk of hemorrhagic stroke, mortality, major bleeding, and ICH by 10% to 71% compared with VKAs but not rivaroxaban. For VTE, NOACs and VKAs were comparable for recurrent VTE/fatal PE/DVT/PE risk in 7 RCTs and 1 observational study. The 7 RCTs demonstrated a 32% to 69% decreased risk of major bleeding for dabigatran, rivaroxaban, and apixaban compared with VKAs. No difference was shown in 1 rivaroxaban observational study (HR, 0.77 [95% CI, 0.40-1.49]) and 1 edoxaban RCT (HR, 0.84 [95% CI, 0.59-1.20]). Except for dabigatran, the NOACs had a 61% to 86% decreased risk of ICH and gastrointestinal bleeding.

IMPLICATIONS: Overall, NOACs were comparable or superior to VKAs. Although no observational studies are currently available for apixaban/edoxaban, a few notable inconsistencies exist for dabigatran (ischemic stroke, MI) and rivaroxaban (stroke/SE, major bleeding in VTE) between RCTs and observational studies. Individualizing NOAC/VKA therapy based on benefit/safety profiles and patient characteristics is suggested.

OBJECTIVES: Pain is the most prevalent problem among veterans, who receive pain diagnoses 5 times more frequently than the general population. Opioids are commonly prescribed for pain, but they have potential for misuse and serious adverse events. The study objective was to evaluate opioid dispensing patterns and predictors for overlap in veterans who are eligible for Medicare Part D benefits.

METHODS: A sample of male and all female veterans aged 66 years and older without cancer in 2005-2009 was included. Overlapping days' supply of opioids were evaluated within the U.S. Department of Veterans Affairs (VA), within Part D, and in cross-system users of VA and Part D-reimbursed pharmacies during 2007-2009. Dispensing patterns were analyzed with t tests and chi-square tests. Predictors of overlap were identified with general estimating equations.

RESULTS: At least 1 opioid was dispensed to 88.5% of the sample. In 2006 after Part D implementation, 55.2% of opioids were dispensed by VA, decreasing to 44.3% in 2009 (P <0.0001). Opioids dispensed from Part D-reimbursed pharmacies had a higher frequency of overlap compared to those filled at a VA facility (P <0.0001). While overlapping days' supply for opioids filled at VA decreased, overlap increased for prescriptions filled at Part D-reimbursed pharmacies (P <0.0001). There was minimal overlap in opioids between systems, but cross-system use increased over the study period. Predictors for overlap include females, Part D enrollment, no VA medication copay, sleep disorders, psychiatric diagnoses, and substance or alcohol abuse (all P <0.01). Veterans who were Hispanic, older, and had higher incomes had lower overlap odds (all P <0.0001).

CONCLUSIONS: Opioids dispensed from Part D-reimbursed pharmacies had a higher frequency of overlapping days' supply as compared to those filled by the VA, but there was minimal overlap between systems. While overlapping opioid prescriptions filled by the VA decreased from 2007 to 2009, overlap increased for prescriptions filled at Part D-reimbursed pharmacies. Tools, such as drug monitoring programs, should be used by VA and non-VA providers to decrease opioid-related harms and misuse.

BACKGROUND: The Veterans Choice Program (VCP) was created to ensure timely access to health care in the Department of Veterans Affairs (VA). Under this program, medications may be ordered by select non-VA clinicians to be dispensed by VA pharmacies, creating new challenges in ensuring medication safety.

OBJECTIVES: To examine pharmaceutical use during the first year of the VCP and to understand barriers and facilitators for VA pharmacists to dispensing medications under the VCP.

STUDY DESIGN: Mixed-methods evaluation.

METHODS: We captured all prescriptions dispensed through the VCP and described the demographics of VCP users and their medications. We also conducted semistructured interviews of VA pharmacists, focusing on VA formulary management and experiences dispensing opioid and hepatitis C (HCV) medications. Codebook development and coding followed iterative qualitative methods.

RESULTS: Overall, 17,346 Veterans received 56,426 VCP prescriptions from November 7, 2014 through November 7, 2015. The total medication cost was $27 million, 90% of which was for only 2772 HCV prescriptions. Topical eye drops and opioids represented the most commonly dispensed prescriptions (15.6% and 9.2% of all prescriptions, respectively). Pharmacists reported numerous challenges to dispensing VCP medications, including time required to contact non-VA clinicians about formulary issues, requiring controlled substance prescriptions to be hand delivered to VA pharmacies, and lack of access to laboratory data required to safely dispense medications.

CONCLUSIONS: HCV-related medication costs predominated the first year of VCP, but this is likely to change going forward. The safe use of opioids, efficient management of nonformulary medications, and unintended new barriers to access created by the VCP must be addressed.

OBJECTIVE: Underuse of clozapine and overuse of antipsychotic polypharmacy are both indicators of poor quality of care. This study examined variation in prescribing clozapine and antipsychotic polypharmacy across providers, as well as factors associated with these practices.

METHODS: Using 2010-2012 Pennsylvania Medicaid data, prescribers were identified if they wrote antipsychotic prescriptions for ten or more nonelderly adult patients with schizophrenia annually. Generalized linear mixed models with a binomial distribution and a logit link were used to examine prescriber-level annual percentages of patients with clozapine use and with long-term (≥90 days) antipsychotic polypharmacy and associated characteristics of prescribers' patient caseloads, prescriber characteristics, and Medicaid payer (fee-for-service versus managed care plans).

RESULTS: The study cohort included 645 prescribers in 2010, 632 in 2011, and 650 in 2012. In 2012, the mean prescriber-level annual percentage of patients with any clozapine use was 7% (range 0%-89%), and the mean percentage of patients with any long-term antipsychotic polypharmacy was 7% (range 0%-45%) (similar rates were found during 2010-2012). Prescribers with high prescription volume, a smaller percentage of patients from racial or ethnic minority groups, and a larger percentage of patients eligible for Supplemental Security Income were more likely to use both clozapine and antipsychotic polypharmacy for treating schizophrenia. Prescriber specialty and Medicaid payer were also associated with prescribers' practices.

CONCLUSIONS: Considerable variation was found in clozapine and antipsychotic polypharmacy practices across prescribers in their treatment of schizophrenia. Targeting efforts to selected prescribers holds promise as an approach to promote evidence-based antipsychotic prescribing.

OBJECTIVES: The US opioid medication epidemic has resulted in serious health consequences for patients. Formulary management tools adopted by payers, specifically prior authorization (PA) policies, may lower the rates of opioid medication abuse and overdose. We compared rates of opioid abuse and overdose among enrollees in plans that varied in their use of PA from "High PA" (ie, required PA for 17 to 74 opioids), with "Low PA" (ie, required PA for 1 opioid), and "No PA" policies for opioid medications.

STUDY DESIGN: Retrospective cohort study of patients initiating opioid treatment in Pennsylvania Medicaid from 2010 to 2012.

METHODS: Generalized linear models with generalized estimating equations were employed to assess the relationships between the presence of PA policies and opioid medication abuse and overdose, as measured in Medicaid claims data, adjusting for demographics, comorbid health conditions, benzodiazepine/muscle relaxant use, and emergency department use.

RESULTS: The study cohort included 297,634 enrollees with a total of 382,828 opioid treatment episodes. Compared with plans with No PA, enrollees in High PA (adjusted rate ratio [ARR], 0.89; 95% confidence interval [CI], 0.85-0.93; P <.001) and Low PA plans (ARR, 0.93; 95% CI, 0.87-1.00; P = .04) had lower rates of abuse. Enrollees in the Low PA plan had a lower rate of overdose than those within plans with No PA (ARR, 0.75; 95% CI, 0.59-0.95; P = .02). High PA plan enrollees were also less likely than No PA enrollees to experience an overdose, but this association was not statistically significant (ARR, 0.88; 95% CI, 0.76-1.02; P = .08).

CONCLUSIONS: Enrollees within Medicaid plans that utilize PA policies appear to have lower rates of abuse and overdose following initiation of opioid medication treatment.