Effectiveness and safety in non-valvular atrial fibrillation patients switching from warfarin to direct oral anticoagulants in US healthcare claims.

INTRODUCTION: There is a paucity of real-world studies examining the risks of stroke/systemic embolism (SE) and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients switching from warfarin to a direct oral anticoagulant (DOAC). This retrospective study was conducted to compare the stroke/SE and MB risks between patients switched from warfarin to apixaban, dabigatran, or rivaroxaban in real-world clinical practice. MATERIALS AND METHODS: This study used data from four United States commercial claims databases from January 1, 2012 to June 30, 2019. The study population included NVAF patients initially treated with warfarin and switched to apixaban, dabigatran, or rivaroxaban within 90 days of their warfarin prescription ending. Patients were matched 1:1 between the DOACs in each database using propensity scores and then pooled for the final analysis. Cox proportional hazards models were used to calculate the risk of stroke/SE and MB. RESULTS AND CONCLUSIONS: The final population consisted of 2,611 apixaban-dabigatran, 12,165 apixaban-rivaroxaban, and 2,672 dabigatran-rivaroxaban pairs. Apixaban vs. dabigatran was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.39-0.96) and MB (HR: 0.67; 95% CI: 0.50-0.91). Apixaban vs. rivaroxaban was associated with a similar risk of stroke/SE (HR: 0.88; 95% CI: 0.73-1.07) and a lower risk of MB (HR: 0.60; 95% CI: 0.52-0.68). There was no significant difference in either risk between dabigatran and rivaroxaban. These results provide important insights into how the risks of stroke/SE and MB for NVAF patients vary when switching from warfarin to different DOACs.

Contemporary Predictors of Major Adverse Cardiovascular Events Following Percutaneous Coronary Intervention: A Nationally Representative US Sample.

Background: Patient outcomes after percutaneous coronary intervention (PCI) have improved over the last 30 years due to better techniques, therapies, and care processes. This study evaluated contemporary predictors of post-PCI major adverse cardiovascular events (MACE) and summarized risk in a parsimonious risk prediction model. Methods: The Cardiovascular Patient-Level Analytical Platform (CLiPPeR) is an observational dataset of baseline variables and longitudinal outcomes from the American College of Cardiology's CathPCI Registry® and national claims data. Cox regression was used to evaluate 2-6 years of patient follow-up (mean: 2.56 years), ending in December 2017, after index PCI between 2012 and 2015 (N = 1,450,787), to examine clinical and procedural predictors of MACE (first myocardial infarction, stroke, repeat PCI, coronary artery bypass grafting, and mortality). Cox analyses of post-PCI MACE were landmarked 28 days after index PCI. Results: Overall, 12.4% (n = 179,849) experienced MACE. All variables predicted MACE, with cardiogenic shock, cardiac arrest, four diseased coronary vessels, and chronic kidney disease having hazard ratios (HRs) ≥ 1.50. Other major predictors of MACE were in-hospital stroke, three-vessel disease, anemia, heart failure, and STEMI presentation. The index revascularization and discharge prescription of aspirin, P2Y12 inhibitor, and lipid-lowering medication had HR ≤ 0.67. The primary Cox model had c-statistic c = 0.761 for MACE versus c = 0.701 for the parsimonious model and c = 0.752 for the parsimonious model plus treatment variables. Conclusions: In a nationally representative US sample of post-PCI patients, predictors of longitudinal MACE risk were identified, and a parsimonious model efficiently encapsulated them. These findings may aid in assessing care processes to further improve care post-PCI outcomes.

Clinical Impact of Switching or Continuation of Apixaban or Rivaroxaban among Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND: Real-world evidence on direct oral anticoagulant outcomes among Non-Valvular Atrial Fibrillation (NVAF) patients is limited. We aimed to evaluate stroke/systemic embolism (SE) and major bleeding (MB) risks among NVAF patients continuing or switching to different oral anticoagulants. METHODS: Using Optum's de-identified Clinformatics® Data Mart Database, we identified NVAF patients initiating apixaban or rivaroxaban between 1 January 2013 and 31 December 2021. Patients switching therapies within 30 days before or 90 days after discontinuing their initial DOAC and those who continued initial therapy were included. The index date was the switch date for switchers, while continuers were assigned a hypothetic index date. Switchers and continuers were propensity score matched based on pre-index characteristics. RESULTS: Among 167,868 apixaban and 65,888 rivaroxaban initiators, 2900 apixaban-to-rivaroxaban switchers were matched with 14,500 apixaban continuers, and 2873 rivaroxaban-to-apixaban switchers were matched with 14,365 rivaroxaban continuers. Apixaban-to-rivaroxaban switching was associated with higher stroke/SE risk (HR: 1.99, 95% CI: 1.38-2.88) and MB risk (HR:1.80, 95% CI: 1.46-2.23) than continuing apixaban. Rivaroxaban-to-apixaban switching had similar stroke/SE risk (HR: 0.74, 95% CI: 0.45-1.22) but lower MB risk (HR: 0.49, 95% CI: 0.38-0.65) than continuing rivaroxaban. CONCLUSIONS: These findings may aid physicians and patients in making informed decisions when considering a switch between apixaban and rivaroxaban.

Journey to anticoagulant access following payer rejection of apixaban.

OBJECTIVES: To investigate the journey to oral anticoagulant (OAC) access following formulary-related rejection of apixaban (Eliquis) and evaluate characteristics associated with failure to achieve OAC access among patients with atrial fibrillation (AF). STUDY DESIGN: Retrospective study using the Optum Market Clarity Data from January 2016 through February 2020. METHODS: Patients had at least 1 claim rejection for apixaban due to prior authorization (PA), formulary exclusion (FE), or quantity limit (QL) and at least 1 AF diagnosis on or before the rejected claim. Descriptive statistics summarized transaction journeys by type of formulary restriction. Multivariable regression assessed patient characteristics associated with not receiving an OAC within 60 days after initial rejection. RESULTS: Among 18,434 patients in the analytic sample, QL was the most common reason for rejection (68.7%), followed by PA (21.2%) and FE (10.2%). Most patients received a paid OAC claim within 60 days after rejection (82.2%-85.5% across restriction types). Mean time from rejection to paid claim ranged from 5.2 to 10.7 days among patients with a paid OAC claim and 12.4 to 17.6 days among those with multiple attempts before OAC receipt. Characteristics associated with higher odds of not receiving OAC treatment included being male, beingAfrican American, having Medicaid coverage, possessing a high stroke risk score, exhibiting no evidence of prior apixaban treatment, and being prescribed a low dose of apixaban on the initial rejected claim. CONCLUSIONS: Most patients with a claim rejection for apixaban received approval for apixaban within 60 days, suggesting that initial rejection merely created a delay in treatment. Vulnerable populations were at greater risk of not receiving a paid OAC claim.

The Association between Direct Oral Anticoagulants Prescribing Behavior and Non-Valvular Atrial Fibrillation Outcomes: An Instrumental Variable Analysis of Real-World Data.

Several observational studies have compared apixaban with rivaroxaban in patients with non-valvular atrial fibrillation (NVAF), but these analyses may be confounded by unmeasured characteristics. This study used provider prescribing preference (PPP) as an instrumental variable (IV) to assess the association between prescriber choice of rivaroxaban vs. apixaban and the study outcomes of stroke/systemic embolism (SE), major bleeding, and death in a retrospective cohort of NVAF patients in the US. Initiators of either medication were linked to their prescribers and followed until the first of the study outcome, the end of rivaroxaban/apixaban use, or 365 days after initiation. PPP for each patient was the percent of rivaroxaban initiations issued by the provider for the prior 10 NVAF patients. Cox regression models tested associations between quintiles of PPP and each outcome. A total of 61,155 patients and 1726 providers were included. The IV was a strong predictor of rivaroxaban prescription (OR = 17.9; 95% CI: 16.6, 19.3). There were statistically significant associations between increasing preference for rivaroxaban and rates of major bleeding (ptrend = 0.041) and death (ptrend = 0.031), but not stroke/SE (ptrend = 0.398). This analysis provides evidence of the relative safety of apixaban over rivaroxaban for the risk of major bleeding and death.

Payer formulary tier increases of apixaban: how patients respond and potential implications.

OBJECTIVE: To assess potential impacts of formulary tier increases of apixaban-an efficacious oral anticoagulant (OAC) for preventing stroke in patients with atrial fibrillation (AF)-on patients' prescription drug plan (PDP) switching and OAC treatment patterns. METHODS: Nationwide claims data for Medicare beneficiaries with Parts A, B, and D (100% sample) were used to assess apixaban-treated AF patients who faced a formulary tier increase for apixaban in 2017 by their Part D PDP. Patients' out-of-pocket (OOP) costs for apixaban were described, along with PDP switching and OAC treatment patterns. RESULTS: Among 1845 included patients, 97.7% had apixaban on tier 3 of their plan's formulary in 2016 and faced its increase to tier 4 for 2017. Approximately 4% (N = 81) of patients pre-emptively switched to a different PDP for 2017 with almost all switching to plans with apixaban on a lower formulary tier and 85.2% continuing apixaban treatment. Among the 96% (N = 1764) of patients who remained on the same PDP for 2017, over half (57.5%) continued apixaban treatment, despite increased OOP costs ($54 vs. $135 for a 30-day supply in 2016 vs. 2017). Only 12.4% of those who remained on the same plan for 2017 switched to another OAC, while as much as 30.1% discontinued OACs. These discontinuers exhibited higher comorbidity burdens than patients continuing on any OAC. CONCLUSION: The majority of patients continued on apixaban despite higher OOP cost, suggesting patients' reluctance to change treatment for non-medical reasons; however, 30% of patients discontinued OAC treatment after higher apixaban tier placement.

A Real-World Evaluation of Primary Medication Nonadherence in Patients with Nonvalvular Atrial Fibrillation Prescribed Oral Anticoagulants in the United States.

BACKGROUND: Nonadherence to oral anticoagulants (OACs) is a challenge to stroke risk reduction in patients with nonvalvular atrial fibrillation (NVAF). Data on primary medication nonadherence (PMN) in NVAF are lacking. OBJECTIVES: Our aim was to assess the rates and predictors of PMN among NVAF patients who were newly prescribed an OAC. METHODS: This was a retrospective database analysis of linked healthcare claims and electronic health record data. Adult NVAF patients with a prescription order for an OAC (apixaban, rivaroxaban, dabigatran, or warfarin) between January 2016 and June 2019 were identified (date of first prescription order = index date). Patients had a 1-year baseline and a 6-month post-index period to assess the rates of PMN, defined as having a prescription order but no paid claim for any OAC on or within 30 days after the index date. Sensitivity analyses explored 60-, 90- and 180-day PMN thresholds. Logistic regression models were used to examine the predictors of PMN. RESULTS: Among 20,393 patients, the overall 30-day PMN rate was 28.4%; PMN rates decreased to 17% with a 180-day threshold. PMN was numerically lowest for warfarin among OACs and numerically lowest for apixaban among direct OACs. A CHA2DS2-VASc score of ≥ 3, commercial insurance, and African American race were associated with higher odds of PMN. CONCLUSIONS: More than one-quarter of patients experienced PMN within 30 days of their initial prescription order. This rate decreased over a longer period, suggesting a delay in fills. Understanding the factors associated with PMN is warranted to develop effective interventions for improving OAC treatment rates in NVAF.

Effectiveness and Safety of Direct Oral Anticoagulants Among Patients with Non-valvular Atrial Fibrillation and Multimorbidity.

INTRODUCTION: In the USA, there is a steady rise of atrial fibrillation due to the aging population with increased morbidity. This study evaluated the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among elderly patients with non-valvular atrial fibrillation (NVAF) and multimorbidity prescribed direct oral anticoagulants (DOACs). METHODS: Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January 1, 2012 to December 31, 2017 was conducted. High multimorbidity was classified as having ≥ 6 comorbidities. Cox proportional hazard models were used to evaluate the hazard ratios of S/SE and MB among three 1:1 propensity score matched DOAC cohorts. All-cause healthcare costs were estimated using generalized linear models. RESULTS: Overall 36% of the NVAF study population had high multimorbidity, forming three propensity score matched (PSM) cohorts: 12,511 apixaban-dabigatran, 60,287 apixaban-rivaroxaban, and 12,567 dabigatran-rivaroxaban patients. Apixaban was associated with a lower risk of stroke/SE and MB when compared with dabigatran and rivaroxaban. Dabigatran had a lower risk of stroke/SE and a similar risk of MB when compared with rivaroxaban. Compared to rivaroxaban, apixaban patients incurred lower all-cause healthcare costs, and dabigatran patients incurred similar all-cause healthcare costs. Compared to dabigatran, apixaban patients incurred similar all-cause healthcare costs. CONCLUSION: Patients with NVAF and ≥ 6 comorbid conditions had significantly different risks for stroke/SE and MB when comparing DOACs to DOACs, and different healthcare expenses. This study's results may be useful for evaluating the risk-benefit ratio of DOAC use in patients with NVAF and multimorbidity.

Delaying clinical events among patients with non-valvular atrial fibrillation treated with oral anticoagulants: Insights from the ARISTOPHANES study.

BACKGROUND: Oral anticoagulants (OACs) mitigate stroke and systemic embolism (SE) risk in non-valvular atrial fibrillation (AF) patients but can increase the risk of major bleeding (MB). This study analyzed the gains in event-free time for these outcomes among OAC treatment options represented in the ARISTOPHANES study. METHODS: This sub-analysis consisted of NVAF patients who initiated warfarin, apixaban, dabigatran, or rivaroxaban from 01JAN2013-30SEP2015, with data pooled from Medicare and 4 US commercial claims databases. Propensity score matching was conducted between non-vitamin K antagonist OAC (NOAC) and warfarin cohorts in each database and results were pooled. Laplace regression was used to evaluate the delay in time to stroke/SE and MB events between NOACs and warfarin and between NOACs after the first 12-months of follow-up. RESULTS: The population included 466,991 patients (167,413 warfarin; 108,852 apixaban; 37,724 dabigatran; and 153,002 rivaroxaban). Event-free time gain (95% confidence interval) for apixaban versus warfarin was 101 days (78- 124) for stroke/SE and 116 (103- 130) days for MB. The gain in event-free time for dabigatran versus warfarin was 45 days (3- 87) for stroke/SE and 92 (68- 116) days for MB. The gain in event-free time for rivaroxaban versus warfarin was 63 days (42- 84) for stroke/SE but event-free time decreased by 18 (-31-6) days for MB. CONCLUSIONS: Over 12 months after initiation, apixaban and dabigatran conferred progressive increases in event free time for stroke/SE and MB vs warfarin, whereas rivaroxaban conferred an increase in stroke/SE-free time but a loss in MB-free time vs warfarin.

Payer formulary exclusions of apixaban: how patients respond and potential implications.

In recent years, US payers have increased usage of formulary exclusions as a means to help manage costs. Earlier this year, one of the largest pharmacy benefit managers in the country added Eliquis (apixaban), the most widely used anticoagulant, to its list of excluded medicines from its formulary, raising concerns by physicians and patients. In this commentary, we examine the potential impacts of formulary exclusion of a drug like apixaban-a treatment for patients with atrial fibrillation and venous thromboembolism to help prevent stroke and clotting events and which has been demonstrated to have a strong efficacy and safety profile. We discuss the effect of formulary exclusions on patients' ability to access the most clinically appropriate treatment for their health needs, along with possible effects on their health and well-being. We also report descriptive results on apixaban-treated patients with traditional Medicare coverage who faced a formulary exclusion of apixaban in 2017, and these patients' observed behaviors. We found that the majority of these patients remained on apixaban either through pre-emptively switching to a different Part D drug plan with apixaban coverage or applying for formulary exception. Our findings suggest that formulary exclusion did not help to achieve the goal of switching patients to less costly medications but created additional hurdles for patients to access their preferred treatment and increased patient burden. Alternative ways to manage payer costs may be needed to help avoid poor outcomes and reduce the burden placed on patients in their efforts to access life-saving medications.

Effectiveness and safety of oral anticoagulants in non-valvular atrial fibrillation patients with prior bleeding events: a retrospective analysis of administrative claims databases.

INTRODUCTION: There are a paucity of real-world data examining effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in nonvalvular atrial fibrillation (NVAF) patients with prior bleeding. METHODS: This retrospective analysis included data from 5 insurance claims databases and included NVAF patients prescribed OACs with prior bleeding. One-to-one propensity score matching was conducted between NOACs and warfarin and between NOACs in each database. Cox proportional hazards models were used to evaluate the risk of stroke/systemic embolism (SE) and MB. RESULTS: A total of 244,563 patients (mean age 77; 50% female) with prior bleeding included 55,094 (22.5%) treated with apixaban, 12,500 (5.1%) with dabigatran, 38,246 (15.6%) with rivaroxaban, and 138,723 (56.7%) with warfarin. Apixaban (hazard ratio [HR]: 0.76 [95% CI: 0.70, 0.83]) and rivaroxaban (HR: 0.79 [95% CI: 0.71, 0.87]) had a lower risk of stroke/SE vs. warfarin. Apixaban (HR: 0.67 [95% CI: 0.64, 0.70]) and dabigatran (HR: 0.88 [95% CI: 0.81, 0.96]) had a lower risk of MB vs. warfarin. Apixaban patients had a lower risk of stroke/SE vs. dabigatran (HR: 0.70 [95% CI: 0.57, 0.86]) and rivaroxaban (HR: 0.85 [95% CI: 0.76, 0.96]) and a lower risk of MB than dabigatran (HR: 0.73 [95% CI: 0.67, 0.81]) and rivaroxaban (HR: 0.64 [95% CI: 0.61, 0.68]). CONCLUSIONS: In this real-world analysis of a large sample of NVAF patients with prior bleeding, NOACs were associated with similar or lower risk of stroke/SE and MB vs. warfarin and variable risk of stroke/SE and MB against each other.

Hospitalization for Myocardial Infarction with Ticagrelor or Clopidogrel in Patients with Acute Coronary Syndrome: An On-Treatment Comparative Effectiveness Analysis.

INTRODUCTION: Prescribing patterns and suboptimal adherence present methodological challenges for real-world head-to-head comparisons of ticagrelor and clopidogrel in intent-to-treat studies. The aim of this study was to compare ticagrelor and clopidogrel in an on-treatment population. METHODS: This retrospective cohort study used the Optum™ Clinformatics™ database to identify patients with acute coronary syndrome (ACS) discharged on ticagrelor or clopidogrel between January 1, 2012 and September 30, 2019. The primary end point was hospitalization for myocardial infarction (MI); the secondary end point was hospitalization for major bleeding. The ticagrelor and clopidogrel cohorts were balanced by propensity score matching (PSM) 1:3 for demographic and clinical characteristics. Outcomes were ascertained from day 31 until day 365 or end of follow-up. RESULTS: Of 339,387 patients with ACS, 14,110 ticagrelor- and 57,482 clopidogrel-treated patients met the study criteria. After PSM, 13,373 ticagrelor- and 29,656 clopidogrel-treated patients provided 4945 and 13,895 patient-years of data, respectively, for the primary end point. Hospitalization for MI was significantly lower in the ticagrelor compared to the clopidogrel cohort (2.22 vs. 3.52 per 100 patient-years; 36.8% relative risk reduction [RRR]; P < 0.0001). Hospitalization for major bleeding was similar in the ticagrelor and clopidogrel cohorts (2.04 vs. 2.06 per 100 patient-years; 1.1% RRR, P = 0.9214). CONCLUSIONS: In this real-world on-treatment analysis, hospitalization for MI was significantly lower with ticagrelor compared to clopidogrel, with similar rates of hospitalization for major bleeding. Study findings underscore the importance of being on the appropriate guideline-recommended therapy and support the use of ticagrelor over clopidogrel.

New Heart Failure After Myocardial Infarction (From the National Cardiovascular Data Registries [NCDR] Linked With All-Payer Claims).

Heart failure (HF) is common in patients presenting with acute myocardial infarction (MI), but incidence and predictors of new onset HF after hospitalization for MI are less well characterized. We evaluated patients hospitalized for acute MI without preceding or concurrent HF in the National Cardiovascular Data Registry (NCDR) CathPCI and Chest Pain-MI registries linked with claims data between April 2010 and March 2017. Cumulative incidence and independent predictors of HF after discharge were determined, and a simplified risk score was developed to predict incident HF following MI. In 337,274 patients with acute MI and no history of HF, 8.0% developed incident HF within 1 year after discharge and 18.8% developed HF within 5 years. Significant predictors of HF after MI included advanced chronic kidney disease (CKD) (HR 2.34, 95% confidence interval [CI] 2.23-2.46 for Stage IV vs Stage I, and HR 2.18, 95% CI 2.07-2.29 for Stage V vs. Stage I), recurrent MI following index MI (HR 2.24, 95% CI 2.19-2.28), African-American race (HR 1.44, 95% CI 1.40-1.48), and diabetes (HR 1.39, 95% CI 1.37-1.42). A risk score of 8 variables predicted HF with modest discrimination (optimism-corrected c-statistic 0.64) and good calibration. In conclusion, nearly 1 in 5 patients in a large nationally representative cohort without preceding or concurrent heart failure at time of MI developed incident HF within 5 years after discharge. Advanced CKD and recurrent MI were the strongest predictors of future HF. Increased recognition of specific risk factors for HF may help inform care strategies following MI.

Disease Burden Following Non-Cardioembolic Minor Ischemic Stroke or High-Risk TIA: A GWTG-Stroke Study.

BACKGROUND: Limited real-world data are available on outcomes following non-cardioembolic minor ischemic stroke (IS) or high-risk transient ischemic attack (TIA), particularly in the United States (US). We examined outcomes and Medicare payments following any severity IS or TIA as well as the subgroup with minor IS or high-risk TIA. METHODS: Medicare beneficiaries >65 years were identified using US nationwide Get with the Guidelines (GWTG)-Stroke Registry linked to Medicare claims data. The cohort consisted of patients enrolled in Medicare fee-for-service plan, hospitalized with non-cardioembolic IS or TIA between 2011 and 2014, segmenting a subgroup with minor IS (National Institute of Health Stroke Scale [NIHSS] ≤5) or high-risk TIA (ABCD2-score ≥6) compatible with the THALES clinical trial population. Outcomes included functional status at discharge, clinical outcomes (all-cause mortality, ischemic stroke, and hemorrhagic stroke, individually and as a composite), hospitalizations, and population average inpatient Medicare payments following non-cardioembolic IS or TIA. RESULTS: The THALES-compatible cohort included 62,518 patients from 1471 hospitals. At discharge, 37.0% were unable to ambulate without assistance, and 96.2% were prescribed antiplatelet therapy. Cumulative incidences at 30 days, 90 days, and 1 year for the composite outcome were 3.7%, 7.6%, and 17.2% and 2.4%, 4.0%, and 7.3% for subsequent stroke. The mean Medicare payment for the index hospitalization was $7951. The cumulative all-cause inpatient Medicare spending per patient (with or without any subsequent admission) at 30 days and 1 year from discharge was $1451 and $8105, respectively. CONCLUSIONS: The burden of illness for minor IS/high-risk TIA patients indicates an important unmet need. Improved therapeutic options may offer a significant impact on both patient outcomes and Medicare spending.

Translating clinical evidence into value-based payment models: pooled analyses of innovative real-world outcomes agreements for ticagrelor in the United States.

Innovative value strategies for reimbursement of medications include value-based agreements (VBAs) between payers and pharmaceutical manufacturers, which have the potential to improve affordability and patient access to therapy, as well as lead to a reduction in downstream health events and associated medical costs. VBAs link payment for a medication to its performance in real-world clinical practice measured against prespecified outcomes that are aligned to existing evidence. Given its high prevalence, economic burden, and impact on mortality, cardiovascular disease (namely, coronary heart disease) represents an opportunity for VBAs to contribute to improved health outcomes and patient experiences while reducing or containing total medical costs. AstraZeneca developed a VBA framework directly comparing 2 antiplatelet therapies indicated to treat acute coronary syndrome (ACS)-ticagrelor and clopidogrel-based on the PLATO trial, which demonstrated superiority for ticagrelor in reducing the incidence of recurrent myocardial infarction (MI) in patients with ACS. Between 2015 and 2018, 11 contract-years of VBAs utilizing this framework were implemented in commercial and Part D health insurance plans, totaling nearly 32,000 unique patients in which pooled analyses were conducted. Aggregated VBA results indicate that ticagrelor consistently outperformed expectations in reducing recurrent MI vs clopidogrel, while also illustrating how comparative VBA frameworks of this nature may overcome challenges noted for VBAs and be utilized more broadly in future applications.

Copayment Reduction Voucher Utilization and Associations With Medication Persistence and Clinical Outcomes: Findings From the ARTEMIS Trial.

BACKGROUND: Cost is frequently cited as a barrier to optimal medication use, but the extent to which copayment assistance interventions are used when available, and their impact on evidence-based medication persistence and major adverse cardiovascular events is unknown. METHODS AND RESULTS: The ARTEMIS trial (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) randomized 301 hospitals to usual care versus the ability to provide patients with vouchers that offset copayment costs when filling P2Y12 inhibitors in the 1 year post-myocardial infarction. In the intervention group, we used multivariable logistic regression to identify patient and medication cost characteristics associated with voucher use. We then used this model to stratify both intervention and usual care patients by likelihood of voucher use, and examined the impact of the voucher intervention on 1-year P2Y12 inhibitor persistence (no gap in pharmacy supply >30 days) and major adverse cardiovascular events (all-cause death, myocardial infarction, or stroke). Among 10 102 enrolled patients, 6135 patients were treated at hospitals randomized to the copayment intervention. Of these, 1742 (28.4%) never used the voucher, although 1729 (99.2%) voucher never-users filled at least one P2Y12 inhibitor prescription in the 1 year post-myocardial infarction. Characteristics most associated with voucher use included: discharge on ticagrelor, planned 1-year course of P2Y12 inhibitor treatment, white race, commercial insurance, and higher out-of-pocket medication costs (c-statistic 0.74). Applying this propensity model to stratify all enrolled patients by likelihood of voucher use, the intervention improved medication persistence the most in patients with high likelihood of voucher use (adjusted interaction P=0.03, odds ratio, 1.86 [95% CI, 1.48-2.33]). The intervention did not significantly reduce major adverse cardiovascular events in any voucher use likelihood group, although the odds ratio was lowest (0.86 [95% CI, 0.56-1.16]) among patients with high likelihood of voucher use (adjusted interaction P=0.04). CONCLUSIONS: Among patients discharged after myocardial infarction, those with higher copayments and greater out-of-pocket medication costs were more likely to use a copayment assistance voucher, but some classes of patients were less likely to use a copayment assistance voucher. Patients at low likelihood of voucher use benefitted least from copayment assistance, and other interventions may be needed to improve medication-taking behaviors and clinical outcomes in these patients. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02406677.

Healthcare utilization and costs associated with treatment for opioid dependence.

OBJECTIVE: Opioid use disorder (OUD) can be managed with medication assisted therapy (MAT) (methadone [MET], buprenorphine [BUP], or extended-release naltrexone [XR-NTX]) or counseling alone (non-pharmacological therapy [NPT]). The objective of this study was to evaluate healthcare resource utilization and costs associated with XR-NTX compared with alternative treatments for opioid dependence. METHODS: Adults with a diagnosis of opioid dependence who initiated treatment with XR-NTX, BUP, MET, or NPT between January 1, 2011 and December 31, 2014 were identified in the Truven Health MarketScan Commercial administrative claims database. Healthcare resource utilization, costs (inpatient [IP], emergency department [ED], outpatient [OP], and pharmacy) and adherence were evaluated for each cohort during 12-month baseline and follow-up periods. RESULTS: A total of 29,235 patients were included in the analysis; 1,041, 20,566, 745, and 6,883 received XR-NTX, BUP, MET, and NPT, respectively. Patients in the XR-NTX cohort were significantly younger and had more comorbidities compared with the other cohorts. Patients in the XR-NTX group had the largest percentage decrease in IP and ED utilization and costs from baseline to follow-up. OP and pharmacy costs increased significantly from baseline to follow-up for all cohorts. Overall, there was no significant change in total healthcare costs for the XR-NTX group, whereas the costs increased significantly for other groups (BUP = +43%, MET = +47.7%, NPT = +38.8%). CONCLUSIONS: Healthcare resource utilization and costs increased from baseline to follow-up in BUP, MET, and NPT patients, whereas patients receiving XR-NTX experienced no such increase. This analysis suggests there may be economic value in the use of XR-NTX for OUD.