Publications

OBJECTIVE: To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States.

DESIGN: Observational cohort study.

SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system.

PARTICIPANTS: All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation.

MAIN OUTCOME MEASURES: The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion.

RESULTS: Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses.

CONCLUSIONS: Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.

BACKGROUND: In a cohort of Veterans dually enrolled in the Department of Veterans Affairs (VA) and Medicare Part D, we sought to describe high-dose daily opioid use among Veterans with unexplained gastrointestinal (GI) symptoms and structural GI diagnoses and examine factors associated with high-dose use.

METHODS: We used linked national patient-level data from the VA and Centers for Medicare and Medicaid Services (CMS). We grouped patients into 3 subsets: those with unexplained GI symptoms (e.g., chronic abdominal pain); structural GI diagnoses (e.g., chronic pancreatitis); and those with a concurrent unexplained GI symptom and structural GI diagnosis. High-dose daily opioid use levels were examined as a binary variable [≥ 100 morphine milligram equivalents (MME)/day] and as an ordinal variable (50-99 MME/day, 100-119 MME/day, or ≥ 120 MME/day).

RESULTS: We identified 141,805 chronic GI patients dually enrolled in VA and Part D. High-dose opioid use was present in 11% of Veterans with unexplained GI symptoms, 10% of Veterans with structural GI diagnoses, and 15% of Veterans in the concurrent GI group. Compared to Veterans with only an unexplained GI symptom or structural diagnosis, concurrent GI patients were more likely to have higher daily opioid doses, more opioid days ≥ 100 MME, and higher risk of chronic use. Factors associated with high-dose use included opioid receipt from both VA and Part D, younger age, and benzodiazepine use.

CONCLUSIONS: A significant subset of chronic GI patients in the VA are high-dose opioid users. Efforts are needed to reduce high-dose use among Veterans with concurrent GI symptoms and diagnoses.

This cohort study used Medicaid data to examine trends in the use of and spending for hemophilia pharmaceuticals from 2005 to 2020.

BACKGROUND: List prices of tumor necrosis factor (TNF) inhibitors drastically increased during the last decade, but previous research has shown that half of these increases were offset by rising manufacturer discounts. It remains unclear to what extent manufacturers' discounts have offset increases in list prices of each self-administered injectable TNF inhibitor. Evaluating trends in net prices and discounts at the product level will be paramount in understanding the role of competition in the biologic market. OBJECTIVES: To (a) describe product-level changes in net prices of each self-administered injectable TNF inhibitor available in 2007-2019 and (b) quantify to what extent manufacturer discounts have offset increases in list prices. METHODS: We obtained 2007-2019 pricing data for etanercept, adalimumab, certolizumab, and golimumab from the investment firm SSR Health, which uses company-reported sales to estimate net prices and discounts for brand products manufactured by publicly traded companies. For each drug and year, we calculated annual costs of treatment for patients with rheumatoid arthritis based on list and net prices and discounts in Medicaid and other payers. RESULTS: From 2007-2019, list prices of etanercept and adalimumab increased by 293% and 295%, respectively; however, discounts offset 47% and 45% of these increases, leading to net price increases of 171% and 203%. List prices of golimumab and certolizumab increased by 183% and 182%, respectively, but with discounts offsetting 58% and 59% of these increases, net prices increased by 103% and 109%. Net prices of golimumab started to decrease after 2016, while net prices of adalimumab and certolizumab experienced their first drop in 2019. Across the study period, discounts in Medicaid and in other payers increased, respectively, from 21% to 85% and 6% to 32% for etanercept; from 26% to 88% and 19% to 35% for adalimumab; from 28% to 63% and 22% to 46% for golimumab; and from 29% to 83% and 27% to 47% for certolizumab. CONCLUSIONS: Despite growing manufacturer discounts, net prices of self-administered injectable TNF inhibitors still increased at a mean annual rate of 9.6% in 2007-2019. This led to net prices tripling for adalimumab and more than doubling for etanercept, golimumab, and certolizumab. DISCLOSURES: This study was funded by the Myers Family Foundation. Hernandez is funded by the National Heart, Lung and Blood Institute (grant number K01HL142847). Funding sources had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Hernandez has served on Pfizer's scientific advisory board. The other authors have nothing to disclose.

BACKGROUND: Oral anticoagulation (OAC) is recommended for the prevention of stroke in atrial fibrillation (AF). However, only 50%-60% of AF patients in the United States are treated with OAC, and 60% of them adhere to OAC therapy over time. OBJECTIVES: To (1) compare adherent use of OAC between AF patients who received primary care from practices involved in shared-savings models and patients who received care from practices not involved in shared savings and (2) examine the trend of adherence to OAC over time. Because OAC can save downstream medical costs associated with averted stroke events, we hypothesized that OAC adherence would be higher among patients receiving care from practices involved in shared savings. METHODS: Using 2014-2019 claims data from a health insurer in western Pennsylvania, we identified 20,637 AF patients from 2015-2018. Patients were followed from the first AF diagnosis (index date) for 12 months or until disenrollment. We categorized patients according to the payment model of the practice from which they received primary care: shared savings (n = 8,844) and no shared savings (n = 11,793). The primary outcome was adherent use of OAC therapy, which was defined as having at least 80% of the followup period covered with OAC. Secondary outcomes included adherent use of direct oral anticoagulants (DOACs) and adherent use of warfarin. We constructed logistic regression models to assess the association between involvement in shared savings and adherent use of OAC, while controlling for demographics, clinical characteristics, and index year. RESULTS: 34% of patients in the shared-savings group adhered to OAC, compared with 32.7% in the no shared-savings group (P = 0.04). After adjustment, adherence was higher for the shared-savings group for OAC (adjusted odds ratio [aOR] = 1.07, 95% CI = 1.01-1.14) and warfarin (aOR = 1.11, 95% CI = 1.02-1.20) compared with the no shared-savings group. However, the odds of adherent use of DOACs did not statistically differ between shared savings and no shared savings (aOR = 0.99, 95% CI = 0.91-1.08). The odds of adherent OAC use increased over time: the aOR of adherent use of OAC was 1.21 (95% CI = 1.09-1.34) for index year 2016; 1.50 (95% CI = 1.36-1.67) for 2017; and 1.78 (95% CI 1.60-1.98) for 2018, all compared with 2015. CONCLUSIONS: Receipt of primary care from a practice involved in shared savings was associated with a higher adherent use of OAC and warfarin for patients with atrial fibrillation. Furthermore, adherent use of OAC improved over time for both treatment groups. Our research demonstrates that the alignment of financial incentives between providers and insurers may improve the use of therapies with downstream cost-saving potential. DISCLOSURES: This project was funded by the National Heart, Lung and Blood Institute (grant number K01HL142847). Hernandez has received consulting fees from Pfizer and BMS, outside of the submitted work. The other authors have nothing to disclose.

OBJECTIVES: Geriatric palliative care approaches support deprescribing of antihypertensives in older nursing home (NH) residents with limited life expectancy and/or advanced dementia (LLE/AD) who are intensely treated for hypertension (HTN), but information on real-world deprescribing patterns in this population is limited. We examined the incidence and factors associated with antihypertensive deprescribing.

DESIGN: National, retrospective cohort study.

SETTING AND PARTICIPANTS: Older Veterans with LLE/AD and HTN admitted to VA NHs in fiscal years 2009-2015 with potential overtreatment of HTN at admission, defined as receiving at least 1 antihypertensive class of medications and mean daily systolic blood pressure (SBP) <120 mm Hg.

MEASURES: Deprescribing was defined as subsequent dose reduction or discontinuation of an antihypertensive for ≥7 days. Competing risk models assessed cumulative incidence and factors associated with deprescribing.

RESULTS: Within our sample (n = 10,574), cumulative incidence of deprescribing at 30 days was 41%. Veterans with the greatest level of overtreatment (ie, multiple antihypertensives and SBP <100 mm Hg) had an increased likelihood (hazard ratio 1.75, 95% confidence interval 1.59, 1.93) of deprescribing vs those with the lowest level of overtreatment (ie, one antihypertensive and SBP ≥100 to <120 mm Hg). Several markers of poor prognosis (ie, recent weight loss, poor appetite, dehydration, dependence for activities of daily living, pain) and later admission year were associated with increased likelihood of deprescribing, whereas cardiovascular risk factors (ie, diabetes, congestive heart failure, obesity), shortness of breath, and admission source from another NH or home/assisted living setting (vs acute hospital) were associated with decreased likelihood.

CONCLUSIONS AND IMPLICATIONS: Real-world deprescribing patterns of antihypertensives among NH residents with HTN and LLE/AD appear to reflect variation in recommendations for HTN treatment intensity and individualization of patient care in a population with potential overtreatment. Factors facilitating deprescribing included treatment intensity and markers of poor prognosis. Comparative effectiveness and safety studies are needed to guide clinical decisions around deprescribing and HTN management.

BACKGROUND AND OBJECTIVES: Many kidney transplant recipients enrolled in the Veterans Health Administration are also enrolled in Medicare and eligible to receive both Veterans Health Administration and private sector care. Where these patients receive transplant care and its association with mortality are unknown.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study of veterans who underwent kidney transplantation between 2008 and 2016 and were dually enrolled in Veterans Health Administration and Medicare at the time of surgery. We categorized patients on the basis of the source of transplant-related care (i.e., outpatient transplant visits, immunosuppressive medication prescriptions, calcineurin inhibitor measurements) delivered during the first year after transplantation defined as Veterans Health Administration only, Medicare only (i.e., outside Veterans Health Administration using Medicare), or dual care (mixed use of Veterans Health Administration and Medicare). Using multivariable Cox regression, we examined the independent association of post-transplant care source with mortality at 5 years after kidney transplantation.

RESULTS: Among 6206 dually enrolled veterans, 975 (16%) underwent transplantation at a Veterans Health Administration hospital and 5231 (84%) at a non-Veterans Health Administration hospital using Medicare. Post-transplant care was received by 752 patients (12%) through Veterans Health Administration only, 2092 (34%) through Medicare only, and 3362 (54%) through dual care. Compared with patients who were Veterans Health Administration only, 5-year mortality was significantly higher among patients who were Medicare only (adjusted hazard ratio, 2.2; 95% confidence interval, 1.5 to 3.1) and patients who were dual care (adjusted hazard ratio, 1.5; 95% confidence interval, 1.1 to 2.1).

CONCLUSIONS: Most dually enrolled veterans underwent transplantation at a non-Veterans Health Administration transplant center using Medicare, yet many relied on Veterans Health Administration for some or all of their post-transplant care. Veterans who received Veterans Health Administration-only post-transplant care had the lowest 5-year mortality.

BACKGROUND: Many persons with opioid use disorder (OUD) initiate medication for opioid use disorder (MOUD) with one clinic and switch to another clinic during their course of treatment. These switches may occur for referrals or for unplanned reasons. It is unknown, however, what effect switching MOUD clinics has on continuity of MOUD treatment or on overdoses.

OBJECTIVE: To examine patterns of switching MOUD clinics and its association with the proportion of days covered (PDC) by MOUD, and opioid-related overdose.

DESIGN: Cross-sectional retrospective analysis of Pennsylvania Medicaid claims data.

MAIN MEASURES: MOUD clinic switches (i.e., filling a MOUD prescription from a prescriber located in a different clinic than the previous prescriber), PDC, and opioid-related overdose.

RESULTS: Among 14,107 enrollees, 43.2 % switched clinics for MOUD at least once during the 270 day period. In multivariate regression results, enrollees who were Non-Hispanic black (IRR = 1.43; 95 % CI = 1.24-1.65; p < 0.001), had previous methadone use (IRR = 1.32; 95 % CI = 1.13-1.55; p < 0.001), and a higher total number of office visits (IRR = 1.01; CI = 1.01-1.01; p < 0.001) had more switches. The number of clinic switches was positively associated with PDC (OR = 1.12; 95 % CI = 1.10-1.13). In secondary analyses, we found that switches for only one MOUD fill were associated with lower PDC (OR = 0.97; 95 % CI = 0.95-0.99), while switches for more than one MOUD fill were associated with higher PDC (OR = 1.40; 95 % CI = 1.36-1.44). We did not observe a relationship between opioid-related overdose and clinic switches.

CONCLUSIONS: Lack of prescriber continuity for receiving MOUD may not be problematic as it is for other conditions, insofar as it is related to overdose and PDC.

Objective: Atrial fibrillation (AF) may remain undiagnosed until the development of complications. We aimed to examine the epidemiology and racial/ethnic and rural/urban differences in the frequency of newly diagnosed AF manifesting as ischemic stroke in a nationally representative sample of Medicare beneficiaries. Methods: We used a 5% random sample of Medicare claims to identify patients newly diagnosed with AF in 2016. The primary dependent variable was stroke or transient ischemic attack (TIA) in the 7 days prior to the first AF diagnosis, i.e., stroke or TIA as the initial manifestation of AF. We constructed a multivariable logistic regression to quantify the association between race/ethnicity, urban/rural residence, and the primary dependent variable. Results: Among 39,409 patients newly diagnosed with AF (mean age 77 ± 10 years; 58% women; 7.2% Black, 87.8% White, 5.1% others), 2,819 (7.2%) had ischemic stroke or TIA in the 7 days prior to AF diagnosis. Black patients (adjusted OR [95% CI]: 1.21 [1.05, 1.40], vs. White) and urban residents (1.21 [1.08, 1.35], vs. rural) were at increased risk of stroke as the initial manifestation of AF. Racial differences were larger among patients aged ≥75 years, with adjusted ORs of 1.43 (1.19, 1.73) for Black vs. White patients, but non-significant for those aged <75 (P for interaction = 0.03). Conclusion: We observed significant and important differences in the risk of stroke as initial manifestation of AF between White and Black patients and between rural and urban residents. Our results suggest potential disparities in the identification AF across race/ethnicity groups and urban/rural areas.