Applicability of Pharmacogenomically Guided Medication Treatment during Hospitalization of At-Risk Minority Patients.

Known disparities exist in the availability of pharmacogenomic information for minority populations, amplifying uncertainty around clinical utility for these groups. We conducted a multi-site inpatient pharmacogenomic implementation program among self-identified African-Americans (AA; n = 135) with numerous rehospitalizations (n = 341) from 2017 to 2020 (NIH-funded ACCOuNT project/clinicaltrials.gov#NCT03225820). We evaluated the point-of-care availability of patient pharmacogenomic results to healthcare providers via an electronic clinical decision support tool. Among newly added medications during hospitalizations and at discharge, we examined the most frequently utilized medications with associated pharmacogenomic results. The population was predominantly female (61%) with a mean age of 53 years (range 19-86). On average, six medications were newly prescribed during each individual hospital admission. For 48% of all hospitalizations, clinical pharmacogenomic information was applicable to at least one newly prescribed medication. Most results indicated genomic favorability, although nearly 29% of newly prescribed medications indicated increased genomic caution (increase in toxicity risk/suboptimal response). More than one of every five medications prescribed to AA patients at hospital discharge were associated with cautionary pharmacogenomic results (most commonly pantoprazole/suboptimal antacid effect). Notably, high-risk pharmacogenomic results (genomic contraindication) were exceedingly rare. We conclude that the applicability of pharmacogenomic information during hospitalizations for vulnerable populations at-risk for experiencing health disparities is substantial and warrants continued prospective investigation.

Racial Disparities in Intravenous Bisphosphonate Use Among Older Patients With Multiple Myeloma Enrolled in Medicare.

PURPOSE: Intravenous (IV) bisphosphonates reduce the risk of skeletal-related events in patients with multiple myeloma (MM). However, data describing racial differences in IV bisphosphonate utilization outside of clinical trial settings are limited. We evaluated population-level IV bisphosphonate initiation and discontinuation among patients of age ≥ 65 years with MM. METHODS: We conducted a retrospective cohort study of patients of age ≥ 65 years diagnosed with first primary MM between 2001 and 2011. Patients were identified using the SEER-Medicare linked database and followed through December 2013. Cumulative incidences of IV bisphosphonate initiation and time to discontinuation among users were compared between racial and ethnic groups. In Fine and Gray competing risk models, we estimated subdistribution hazard ratios (SHRs) and 95% CIs for initiation and discontinuation. RESULTS: We included 14,231 eligible patients with MM (median age, 76 years; 52% male). Over a median follow-up of 23.1 months, 54% of patients received at least one IV bisphosphonate dose. Our final analytical sample included 10,456 non-Hispanic (NH) Whites, 2,267 NH Blacks, 548 Asian and Pacific islanders, and 815 Hispanic and Latino patients. A higher proportion of White patients (56.1%) newly received IV bisphosphonates after MM diagnosis compared with NH Blacks (45.4%). Compared with White patients, NH Black patients were less likely to initiate IV bisphosphonates (SHR, 0.74; 95% CI, 0.70 to 0.79) and slightly more likely to discontinue treatment (SHR, 1.10; 95% CI, 1.01 to 1.19). CONCLUSION: Approximately half of the patients with MM of age ≥ 65 years did not receive IV bisphosphonates, with significant delay among racial minority groups. These findings highlight the need for improvement of IV bisphosphonate uptake in patients with MM of age ≥ 65 years.

Clinical trajectories, healthcare resource use, and costs of long-term hematopoietic stem cell transplantation survivors: a latent class analysis.

PURPOSE: To identify patterns of healthcare utilization in allogeneic and autologous hematopoietic stem cell transplantation (HSCT) recipients and evaluate factors associated with high-need and high-cost post-transplantation care. METHODS: Latent class analysis of a retrospective cohort of long-term allogeneic (n = 436) and autologous (n = 888) HSCT survivors within the Truven MarketScan database (2009-2014). We assessed factors associated with the latent classes by comparing post-transplantation healthcare utilization including inpatient admissions and length of stay, emergency room visits, specialist visits, and primary care provider visits. RESULTS: Four utilization classes were identified in allogeneic and autologous HSCT recipients: (i) outpatient specialist care dominant (51.8% and 57.3%), (ii) outpatient primary care dominant (10.3% and 25.7%), (iii) outpatient/inpatient balanced (20.6% and 13.5%), and (iv) inpatient dominant (17.2% and 3.5%). Mean monthly healthcare expenditures in the inpatient dominant utilization class were $41,097 and $25,556 for allogeneic and autologous survivors, respectively, which were two to five times higher compared with other classes during the 2-year post-transplantation period. Factors associated with the high utilization class were transfusion (OR = 1.87, 95% CI 1.06-3.30) and 100-day post-transplant graft-versus-host-disease (OR = 1.76, 95% CI 1.05-2.94) in allogeneic HSCT; higher baseline Charlson comorbidity index (OR = 1.45, 95% CI 1.19-1.76) in autologous HSCT. CONCLUSION: Based on distinct patterns of healthcare utilization following HSCT, we identified factors associated with higher resource utilization and greater healthcare related expenditures. IMPLICATIONS FOR CANCER SURVIVORS: Earlier identification of high-cost and high-need HSCT long-term survivors could pave the way for clinicians to offer more continuous engagement in survivorship care delivery.

Adherence and Persistence with DPP-4 Inhibitors Versus Pioglitazone in Type 2 Diabetes Patients with Chronic Kidney Disease: A Retrospective Claims Database Analysis.

BACKGROUND: Adherence and persistence with diabetes medication play an important role in glycemic control and may differ by medication class. However, there is a lack of research comparing diabetes medications in patients with renal impairment, despite the challenges and higher burden associated with managing this population. OBJECTIVE: To compare adherence and persistence among patients with type 2 diabetes mellitus (T2DM) and nondialysis chronic kidney disease (CKD) treated with dipeptidyl peptidase-4 (DPP-4) inhibitors versus pioglitazone. METHODS: This retrospective cohort study used Truven MarketScan administrative claims databases from 2009 to 2015. One-year adherence for patients with T2DM and nondialysis CKD who initiated therapy with either a DPP-4 inhibitor or pioglitazone was measured by proportion of days covered (PDC) following an initial dispensing, and PDC ≥ 0.80 was coded as adherent. Persistence was calculated as the days between the index date and last day with the index medication on hand, based on the end of the last days supply or the end of follow-up (i.e., 365 days), whichever occurred first. Multivariate logistic regression and Cox proportional hazards models were used to estimate confounder-adjusted differences between the groups for adherence and persistence. RESULTS: The final cohort included 9,019 patients (DPP-4 inhibitors: 7,002; pioglitazone: 2,017). In the adjusted analysis, DPP-4 inhibitor users demonstrated a 1.41 (95% CI = 1.25-1.59) higher odds of being adherent compared with pioglitazone users. Overall adjusted HR for persistence was 0.74 (95% CI = 0.69-0.79), which favored DPP-4 inhibitors compared with pioglitazone. Relative to 2010, persistence with pioglitazone decreased in 2011-2012 and then increased in 2013-2014. In the subgroup analysis, DPP-4 inhibitors first had lower (2010: OR = 0.78, 95% CI = 0.70-0.87; 2011-2012: OR = 0.60, 95% CI = 0.54-0.66) and then similar (2013-2014: OR = 1.03, 95% CI = 0.88-1.19) hazards of nonpersistence compared with pioglitazone. CONCLUSIONS: Among patients with T2DM and nondialysis CKD, the use of DPP-4 inhibitors was associated with better adherence compared with pioglitazone. However, following the approval of generic pioglitazone and associated lower cost sharing after 2012, the magnitude of difference in adherence between the medication classes reduced. Similarly, safety warnings in 2011 and approval of generic products in 2012 may have affected pioglitazone persistence, leading to first higher and then similar hazards for nonpersistence with pioglitazone as compared with DPP-4 inhibitors. These shifts in the results for pioglitazone warrant further investigation and close monitoring of the population initiating this medication. DISCLOSURES: No funding was received for this study. The authors have no conflicts of interest to disclose. An abstract for this study was presented as a podium presentation at the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) 2019 Annual Meeting; May 18-22, 2019; New Orleans, LA.

Bevacizumab Use and the Risk of Arterial and Venous Thromboembolism in Patients with High-Grade Gliomas: A Nested Case-Control Study.

STUDY OBJECTIVE: Bevacizumab is used in the treatment of recurrent glioblastoma, but evidence is limited on the incidence of thromboembolic complications regarding the use of this drug in real-world settings. We evaluated the risk of arterial thromboembolism (ATE) and venous thromboembolism (VTE) associated with the use of bevacizumab among adults diagnosed with high-grade gliomas in a commercially insured U.S. DESIGN: Nested case-control study. DATA SOURCE: Truven Health MarketScan Commercial and Medicare Supplemental health claims databases (2009-2015). PATIENTS: A total of 2157 patients with high-grade gliomas who underwent incident (first-time) craniotomy, radiation, and concurrent temozolomide treatment between 2009 and 2015 were identified. Overall, 25 cases of ATE and 99 cases of VTE were each identified in this cohort, and each case was matched to up to 10 controls (170 for ATE and 819 for VTE) based on sex, age, quarter year of index time, and follow-up duration by using incidence density sampling without replacement from the overall cohort. Controls were at risk for the outcome of interest (ATE or VTE) at the time of case occurrence and survived at least as long as their referent case. MEASUREMENTS AND MAIN RESULTS: Exposure to bevacizumab was determined during inpatient or outpatient encounters between the index date (date of the incident craniotomy) and the ATE or VTE event or corresponding matched control date. Multivariable conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of ATE and VTE separately. A higher proportion of patients with ATE received bevacizumab compared with controls (28% vs 17%; adjusted OR 1.51, 95% CI 0.54-4.24), but this excess in odds was not statistically significant. Similarly, bevacizumab was not significantly associated with VTE (13% vs 9%; adjusted OR 1.40, 95% CI 0.71-2.75). CONCLUSION: We found no significant association between the use of bevacizumab and the occurrence of thromboembolic events in patients with high-grade gliomas, although our study was limited by the small number of ATE events. Because the potential for complications from arterial thrombosis cannot be completely ruled out, further research is needed to confirm the thromboembolic safety of bevacizumab in a larger sample of patients with high-grade gliomas.

Daily costs of hospitalization in non-valvular atrial fibrillation patients treated with anticoagulant therapy.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac rhythm disturbance in the US, with an estimated prevalence of 2.7-6.1 million persons in 2010. OBJECTIVE: This study evaluates the progression of daily hospitalization costs among non-valvular atrial fibrillation (NVAF) patients treated with anticoagulant therapy. METHODS: A claims analysis was conducted with Premier Perspective Comparative Hospital Database records from January 2009-March 2013. Patients of 18 years or older who were diagnosed with NVAF and used anticoagulant therapy were studied. Treatment patterns and mean daily costs of hospitalization per patient as well as total costs of hospitalization were reported. Comparisons of mean daily costs with those of the previous day were presented to identify statistical cost differences between hospitalization days. RESULTS: A total of 375,560 patients were identified; 67,017 with AF as admitting/primary diagnosis, and 308,543 with AF as a secondary diagnosis. The mean age of the overall population, primary AF diagnosis cohort, and secondary AF diagnosis cohort was 73.8, 67.9, and 75.0 years, while their proportion of females was 46.3%, 45.6%, and 46.5%, respectively. The mean length of stay was 6.8 days, 3.7 days, and 7.5 days for the overall population, the primary AF diagnosis cohort, and the secondary AF diagnosis cohort, respectively. For all cohorts, mean daily costs stabilized on the third day (overall population: $2103; primary AF diagnosis cohort: $1505; secondary AF diagnosis cohort: $2208). LIMITATIONS: Claims data may have contained inaccuracies or omissions in coded procedures, diagnoses, or pharmacy claims. CONCLUSION: The study showed that daily hospitalization costs for NVAF patients stabilized on the third day of hospitalization and that any reduction or prolongation in hospital length of stay could have a significant impact on the cost burden associated with AF.

Daily hospitalization costs in patients with deep vein thrombosis or pulmonary embolism treated with anticoagulant therapy.

BACKGROUND: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), affects about 900,000 persons in the United States each year. OBJECTIVES: To quantify the progression of daily hospitalization costs among DVT and PE patients. PATIENTS/METHODS: A retrospective claims analysis was conducted from 01/01/2009 to 03/01/2013 using the Premier Perspective Comparative Hospital Database. Patients≥ 18years of age with an admitting/primary diagnosis of DVT or PE and receiving anticoagulant therapy were identified. Treatment patterns, mean daily costs, and total hospitalization costs were reported for the DVT and PE populations. Comparisons of mean daily costs with those of the previous day were presented to identify statistical cost differences between hospitalization days. RESULTS: A total of 28,953 and 35,550 patients were identified with a diagnosis of DVT and PE, respectively. The daily costs were at their highest during the first three days for DVT patients at $2,321, $1,875, and $1,558, respectively. Similar results were found for PE patients with costs at their highest in the first three days, at $2,981, $2,034, and $1,564, respectively. Among the DVT and PE populations, mean daily costs were $1,594 and $1,735, respectively, and daily hospitalization costs became stable on the third day of the hospitalization (standardized differences<10%). CONCLUSIONS: Daily hospitalization costs of patients with an admitting/primary diagnosis of DVT or PE were high in the first days and became stable on the third day. It was further suggested that any change in the LOS could significantly affect hospitalization costs.

Cost-effectiveness analysis of extended duration anticoagulation with rivaroxaban to prevent recurrent venous thromboembolism.

INTRODUCTION: Extended duration anticoagulation with rivaroxaban for an additional 6-12 months can reduce recurrent venous thromboembolic events (VTE) compared to placebo by ~82%, but at the detriment of increased bleeding. We sought to estimate the cost-effectiveness of extended duration prophylaxis of recurrent VTE with rivaroxaban. MATERIAL AND METHODS: A Markov model was developed to estimate the cost-effectiveness of extended duration rivaroxaban, 20mg daily, compared to placebo using a Medicare perspective, a one-monthcycle length and a 40-year time horizon. The model assumed a cohort of 58-year-old patients who had already completed an initial 6-12 months of anticoagulation with rivaroxaban or a vitamin K antagonist; and whom prescribers had clinical equipoise with respect to the need for continued anticoagulation. Data sources included EINSTEIN-Extension and other published studies of VTE. Outcomes included direct treatment costs (in 2013US$), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: Extended duration rivaroxaban resulted in higher treatment costs ($22,645 vs. $22,083) but yielded greater QALYs (16.167 vs. 16.134) as compared to placebo; corresponding to an ICER of $17,030/QALY gained. Our model was most sensitive to the baseline risk of bleeding and recurrent VTE, the hazard ratio of developing a recurrent event while on rivaroxaban and time horizon. Monte Carlo Simulation suggested rivaroxaban would be cost-effective in 66% of 10,000 iterations, assuming a willingness-to-pay threshold of $50,000/QALY. CONCLUSION: Despite the cost of rivaroxaban and an increased risk of bleeding, extending VTE treatment for an additional 6-12 months with rivaroxaban was found cost-effective compared to the placebo over a 40-year time horizon.

Cost-effectiveness of rivaroxaban compared with enoxaparin plus a vitamin K antagonist for the treatment of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is commonly treated with a low-molecular-weight heparin such as enoxaparin plus a vitamin K antagonist (VKA) to prevent recurrence. Administration of enoxaparin + VKA is hampered by complexities of laboratory monitoring and frequent dose adjustments. Rivaroxaban, an orally administered anticoagulant, has been compared with enoxaparin + VKA in the EINSTEIN trials. The objective was to evaluate the cost-effectiveness of rivaroxaban compared with enoxaparin + VKA as anticoagulation treatment for acute, symptomatic, objectively-confirmed DVT or PE. METHODS: A Markov model was built to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios associated with rivaroxaban compared to enoxaparin + VKA in adult patients treated for acute DVT or PE. All patients entered the model in the 'on-treatment' state upon commencement of oral rivaroxaban or enoxaparin + VKA for 3, 6, or 12 months. Transition probabilities were obtained from the EINSTEIN trials during treatment and published literature after treatment. A 3-month cycle length, US payer perspective ($2012), 5-year time horizon and a 3% annual discount rate were used. RESULTS: Treatment with rivaroxaban cost $2,448 per-patient less and was associated with 0.0058 more QALYs compared with enoxaparin + VKA, making it a dominant economic strategy. Upon one-way sensitivity analysis, the model's results were sensitive to the reduction in index VTE hospitalization length-of-stay associated with rivaroxaban compared with enoxaparin + VKA. At a willingness-to-pay threshold of $50,000/QALY, probabilistic sensitivity analysis showed rivaroxaban to be cost-effective compared with enoxaparin + VKA approximately 76% of the time. LIMITATIONS: The model did not account for the benefits associated with an oral and minimally invasive administration of rivaroxaban. 'Real-world' applicability is limited because data from the EINSTEIN trials were used in the model. Also, resource utilization and costs were based on the US healthcare system. CONCLUSION: Rivaroxaban is a cost-effective option for anticoagulation treatment of acute VTE patients.

A pharmacogenetics service experience for pharmacy students, residents, and fellows.

OBJECTIVE: To utilize a comprehensive, pharmacist-led warfarin pharmacogenetics service to provide pharmacy students, residents, and fellows with clinical and research experiences involving genotype-guided therapy. DESIGN: First-year (P1) through fourth-year (P4) pharmacy students, pharmacy residents, and pharmacy fellows participated in a newly implemented warfarin pharmacogenetics service in a hospital setting. Students, residents, and fellows provided genotype-guided dosing recommendations as part of clinical care, or analyzed samples and data collected from patients on the service for research purposes. ASSESSMENT: Students', residents', and fellows' achievement of learning objectives was assessed using a checklist based on established core competencies in pharmacogenetics. The mean competency score of the students, residents, and fellows who completed a clinical and/or research experience with the service was 97% ±3%. CONCLUSION: A comprehensive warfarin pharmacogenetics service provided unique experiential and research opportunities for pharmacy students, residents, and fellows and sufficiently addressed a number of core competencies in pharmacogenetics.

All-cause and disease-related health care costs associated with recurrent venous thromboembolism.

It was the objective of this study to quantify the risk of complications and the incremental health care costs associated with recurrent VTE events. Health care insurance claims from the Ingenix IMPACT database from 01/2004-09/2008 were analysed. Subjects aged ≥18 years on the date of first recurrent VTE diagnosis with ≥12 months of baseline observation prior to the index recurrent VTE were matched 1:1 with no-recurrent VTE patients based on propensity scores. The risk of developing post-thrombotic syndrome (PTS) and other disease-related diagnoses (thrombocytopenia, superficial venous thrombosis, venous ulcer, pulmonary hypertension, stasis dermatitis, and venous insufficiency) was compared between the recurrent and no-recurrent VTE groups for up to one year. All-cause and disease-related costs per patient per year (PPPY) were calculated. The recurrent VTE and no-recurrent VTE cohorts (8,001 subjects in each group) were matched with respect to age, gender, and comorbidities. The risk ratios (RRs) indicated that the risk of developing post-event complications was significantly higher for the recurrent VTE group compared to the no-recurrent VTE group (RR [95% CI]: PTS: 2.7 [2.4 - 2.9], p-value <0.01). Patients with recurrent VTE had significantly higher average PPPY all-cause costs compared to no-recurrent VTE patients ($86,744 versus $37,525, cost difference: $49,219 [€33,617]; 95% CI= 46,253-51,989). Corresponding disease-related health care costs PPPY were also significantly higher for the recurrent VTE group ($11,120 vs $1,262, cost difference: $9,858 [€6,733]; 95% CI= $9,081-$10,476). In conclusion, in this large matched-cohort study, recurrent VTE patients had significantly higher risk of complications and health care costs compared to no-recurrent VTE patients.

Delivery of optimized inpatient anticoagulation therapy: consensus statement from the anticoagulation forum.

OBJECTIVE: To provide recommendations for optimized anticoagulant therapy in the inpatient setting and outline broad elements that need to be in place for effective management of anticoagulant therapy in hospitalized patients; the guidelines are designed to promote optimization of patient clinical outcomes while minimizing the risks for potential anticoagulation-related errors and adverse events. DATA SOURCES: The medical literature was reviewed using MEDLINE (1946-January 2013), EMBASE (1980-January 2013), and PubMed (1947-January 2013) for topics and key words including, but not limited to, standards of practice, national guidelines, patient safety initiatives, and regulatory requirements pertaining to anticoagulant use in the inpatient setting. Non-English-language publications were excluded. Specific MeSH terms used include algorithms, anticoagulants/administration and dosage/adverse effects/therapeutic use, clinical protocols/standards, decision support systems, drug monitoring/methods, humans, inpatients, efficiency/ organizational, outcome and process assessment (health care), patient care team/organization and administration, program development/standards, quality improvement/organization and administration, thrombosis/ drug therapy, thrombosis/prevention and control, risk assessment/standards, patient safety/standards, and risk management/methods. STUDY SELECTION AND DATA EXTRACTION: Because of this document's scope, the medical literature was searched using a variety of strategies. When possible, recommendations are supported by available evidence; however, because this paper deals with processes and systems of care, high-quality evidence (eg, controlled trials) is unavailable. In these cases, recommendations represent the consensus opinion of all authors and are endorsed by the Board of Directors of the Anticoagulation Forum, an organization dedicated to optimizing anticoagulation care. The board is composed of physicians, pharmacists, and nurses with demonstrated expertise and experience in the management of patients receiving anticoagulation therapy. DATA SYNTHESIS: Recommendations for delivering optimized inpatient anticoagulation therapy were developed collaboratively by the authors and are summarized in 8 key areas: (1) process, (2) accountability, (3) integration, (4) standards of practice, (5) provider education and competency, (6) patient education, (7) care transitions, and (8) outcomes. Recommendations are intended to inform the development of coordinated care systems containing elements with demonstrated benefit in improvement of anticoagulation therapy outcomes. Recommendations for delivering optimized inpatient anticoagulation therapy are intended to apply to all clinicians involved in the care of hospitalized patients receiving anticoagulation therapy. CONCLUSIONS: Anticoagulants are high-risk medications associated with a significant rate of medication errors among hospitalized patients. Several national organizations have introduced initiatives to reduce the likelihood of patient harm associated with the use of anticoagulants. Health care organizations are under increasing pressure to develop systems to ensure the safe and effective use of anticoagulants in the inpatient setting. This document provides consensus guidelines for anticoagulant therapy in the inpatient setting and serves as a companion document to prior guidelines relevant for outpatients.

Pharmacoeconomic implications of thromboprophylaxis with new oral anticoagulants after total hip or knee replacement in the USA.

INTRODUCTION: Adequate thromboprophylaxis after total hip or knee replacement (THR or TKR) is essential to reduce the incidence of venous thromboembolism (VTE) and its associated complications. Although effective, traditional anticoagulants are associated with a considerable economic burden, particularly when used outside the hospital setting. This article explores whether newer oral anticoagulants can reduce costs of VTE prophylaxis and therapy. AREAS COVERED: Cost associated with vitamin K antagonists; indirect costs associated with complicated or inconvenient anticoagulation regimens, non-adherence and associated complications; potential of the newer oral anticoagulants, including direct thrombin inhibitors and direct factor Xa inhibitors, to produce indirect cost savings after THR or TKR through a potential reduction in VTE rates and administration and monitoring costs. EXPERT OPINION: The use of new anticoagulants for VTE prophylaxis after THR or TKR can result in direct and indirect cost savings through improved efficacy by reducing VTE rates and decreased drug administration and monitoring costs compared with traditional anticoagulants. Future research will need to focus on cost analyses driven by clinical outcomes measured on the performance of these agents in actual clinical practice.

All-cause and potentially disease-related health care costs associated with venous thromboembolism in commercial, Medicare, and Medicaid beneficiaries.

BACKGROUND: Patients with venous thromboembolism (VTE) are at increased risk of developing recurrent VTE and post-thrombotic syndrome (PTS), a complication of deep vein thrombosis (DVT) characterized by venous reflux and residual venous obstruction that may manifest as chronic pain and swelling. Therefore, formulary/policy decision makers should understand the clinical and economic consequences associated with VTE. OBJECTIVES: To describe the real-world clinical complications, such as recurrent VTE and PTS, associated with VTE and quantify the incremental direct all-cause and potentially disease-related health care costs associated with VTE. METHODS: Health insurance claims between January 2004 and December 2008 from the Ingenix Impact database were used. Adult patients with an initial VTE diagnosis (index DVT, pulmonary embolism [PE], or both) with at least 12 months of enrollment prior to the index VTE were matched 1:1 with comparison patients without VTE. Matching criteria included demographic factors, baseline health care costs, and diagnoses of VTE risk factors such as multiple traumas, malignant cancer, or major surgery. Each patient's observation period began on the date of the index VTE, or corresponding study index date for comparison cases, and ended on the earliest of 1 year after the study index date, the health plan disenrollment date, or December 31, 2008. The proportions of patients with (a) recurrent hospital-documented VTE, defined as an inpatient episode with a diagnosis of VTE in any claim field; (b) PTS; and (c) other potentially disease-related diagnoses (thrombocytopenia, superficial venous thrombosis, venous ulcer, pulmonary hypertension, stasis dermatitis, and venous insufficiency) were calculated. Health care costs were defined as standardized net provider payments after subtraction of member cost-sharing amounts. All-cause incremental health care costs and disease-related costs, defined as provider payments for hospitalization or outpatient claims with a primary or secondary diagnosis of VTE, PTS, or any of the potentially disease-related diagnoses, were computed. Costs were calculated per patient per year (PPPY) by weighting each patient's total cost for up to 1 year post-index by the length of follow-up. RESULTS: The matched VTE and no-VTE cohorts included 16,969 subjects in each group. The index VTE event was DVT, PE, or both in 12,711, 2,473, and 1,785 patients, respectively. In the VTE cohort, the risks of recurrent VTE and PTS during the follow-up period (mean [SD] observation of 271.7 [121.6] days) were 3.6% and 7.1%, respectively. Patients with VTE had significantly higher average PPPY all-cause costs compared with the no-VTE patients (mean [SD] $33,531 [$70,393] vs. $17,590 [$42,011]; cost difference = $15,941, 95% CI = $14,819-$17,012). Corresponding potentially disease-related health care costs PPPY were also significantly higher for the VTE group (mean [SD] $3,141 [$17,055] vs. $228 [$3,221]; cost difference = $2,913, 95% CI = $2,693-$3,157) and represented 18.3% (i.e., $2,913 of $15,941) of the all-cause cost difference between the 2 groups. CONCLUSIONS: In this large matched-cohort study, VTE was associated with a 3.6% risk of hospital-documented recurrence and a 7.1% risk of PTS up to 1 year after index VTE. Potentially disease-related costs represented approximately one-fifth of the incremental all-cause costs associated with VTE.

A clinician's guide to perioperative bridging for patients on oral anticoagulation.

Updates in recent clinical guidelines have led to a change in the management of perioperative anticoagulation for patients on oral anticoagulant therapy. No standardized bridging consensus exists in the literature. The necessity for bridging therapy is determined based on careful consideration of the thrombosis risk versus the bleeding risk of the procedure. Risk stratification will aid the decision to bridge or not to bridge. Patients are bridged with agents with appropriate kinetics to allow for their elimination prior to the time of the procedure in order to decrease the risk of hemorrhage during invasive procedures. This intent of this article is to discuss perioperative bridging therapy and provide a practical guide for the clinician.

Postdischarge oral versus injectable anticoagulation following major orthopedic surgery.

BACKGROUND: Multiple clinical studies have shown postdischarge anticoagulation to be beneficial following major orthopedic surgery (MOS); however, outpatient prophylaxis is not widely practiced. OBJECTIVE: To quantify, from a third-party payer perspective, real-world clinical and economic outcomes for patients receiving injectable or oral anticoagulation as prophylaxis for venous thromboembolism (VTE) following discharge after MOS. METHODS: A retrospective database analysis was conducted using outpatient medical and pharmacy data from the PharMetrics Patient-Centric Database (January 1, 2002, to March 31, 2006). Patients greater than 18 years of age with 9 months of continuous eligibility who received an anticoagulant in the outpatient setting following MOS were eligible. Patients were stratified into 2 cohorts: injectable (dalteparin, enoxaparin, fondaparinux) and oral (warfarin), and were matched 1:1 on demographic and clinical characteristics. RESULTS: A total of 12,724 patients were included (injectable, 6362; oral, 6362). At 90 days, patients receiving oral anticoagulation were 20% more likely to experience a VTE than were those receiving an injectable agent (7.4% vs 6.3%; p = 0.02, OR 1.18; 95% CI 1.03 to 1.36). No significant differences in bleeding were observed (<0.4%). The average adjusted total 6-month costs were significantly (p < 0.001) higher for the oral versus injectable cohort ($18,039 vs $16,429). Medical costs in the oral cohort offset the higher pharmacy costs in the injectable cohort. CONCLUSIONS: This study demonstrates that the risk of VTE extends to the outpatient setting following MOS, even with postdischarge anticoagulation. Injectable agents used in the outpatient setting may result in fewer clinical VTEs without increasing the risk for major bleeding. These findings support the data from controlled clinical studies and expand the evidence to the real-world setting. Despite higher pharmacy acquisition costs for injectable anticoagulants, injectable agents may offer significant per patient savings to third party payers.

Burden of deep vein thrombosis in the outpatient setting following major orthopedic surgery.

BACKGROUND: Venous thromboembolism (VTE) is a known complication of major orthopedic surgery (MOS) with important clinical and economic consequences. Recently published orthopedic guidelines have focused on prevention of pulmonary embolism as a primary outcome, but deep vein thrombosis (DVT) occurrence should not be readily dismissed. OBJECTIVE: To describe the burden of DVT following hospital discharge for MOS by assessing the impact of DVT on costs and resource utilization from the third-party payer perspective. METHODS: Retrospective analysis used outpatient medical and pharmacy data from the PharMetrics Patient-Centric Database (January 1, 2002-March 31, 2006). Patients 18 years of age or older with a record of MOS were eligible for inclusion. Included patients were stratified based on the presence of a DVT during the first month after hospital discharge. Characteristics of the samples were described. The impact of DVT on total 6-month costs and resource utilization (readmissions, outpatient, emergency department visits) was assessed through statistical models. RESULTS: Of the 32,899 patients in the analysis, 1221 (3.71%) had a record of DVT during the first month following discharge for MOS. Compared with patients who did not develop DVT, patients who developed DVT postdischarge were slightly older (56.5 vs 55.8 y; p = 0.0127), had a higher occurrence of prior VTE (26.2% vs 3.4%; p < 0.0001), and had undergone recent surgical procedures other than MOS (73.0% vs 69.6%; p = 0.0116). After controlling for potential confounders, DVT was associated with a 22% and 74% increase in the average number of expected outpatient and emergency department visits, respectively, during the 6-month postdischarge period but did not significantly impact the number of readmissions. Furthermore, total 6-month costs were significantly higher for patients who developed DVT, with an incremental increase of over $2000. CONCLUSIONS: The burden of DVT following hospital discharge for MOS is substantial. Specifically, DVT increases total costs and outpatient and emergency department visits.

Delivery of optimized anticoagulant therapy: consensus statement from the Anticoagulation Forum.

OBJECTIVE: To provide recommendations, policies, and procedures pertaining to the provision of optimized anticoagulation therapy designed to achieve desired clinical endpoints while minimizing the risk of anticoagulant-related adverse outcomes (principally bleeding and thrombosis). STUDY SELECTION AND DATA EXTRACTION: Due to this document's scope, the medical literature was searched using a variety of strategies. When possible, recommendations are supported by available evidence; however, because this paper deals with processes and systems of care, high-quality evidence (eg, controlled trials) is unavailable. In these cases, recommendations represent the consensus opinion of all authors who constitute the Board of Directors of The Anticoagulation Forum, an organization dedicated to optimizing anticoagulation care. The Board is composed of physicians, pharmacists, and nurses with demonstrated expertise and significant collective experience in the management of patients receiving anticoagulation therapy. DATA SYNTHESIS: Recommendations for delivering optimized anticoagulation therapy were developed collaboratively by the authors and are summarized in 9 key areas: (I) Qualifications of Personnel, (II) Supervision, (III) Care Management and Coordination, (IV) Documentation, (V) Patient Education, (VI) Patient Selection and Assessment, (VII) Laboratory Monitoring, (VIII) Initiation and Stabilization of Warfarin Therapy, and (IX) Maintenance of Therapy. Recommendations are intended to inform the development of care systems containing elements with demonstrated benefit in improvement of anticoagulation therapy outcomes. Recommendations for delivering optimized anticoagulation therapy are intended to apply to all clinicians involved in the care of outpatients receiving anticoagulation therapy, regardless of the structure and setting in which that care is delivered. CONCLUSIONS: Anticoagulation therapy, although potentially life-saving, has inherent risks. Whether a patient is managed in a solo practice or a specialized anticoagulation management service, a systematic approach to the key elements outlined herein will reduce the likelihood of adverse events. The need for continued research to validate optimal practices for managing anticoagulation therapy is acknowledged.

Economic evaluation of the use of enoxaparin in non-ST-elevation acute coronary syndrome.

This paper reviews the published literature on the costs and benefits of low-molecular-weight heparins (LMWHs) compared with unfractionated heparin (UFH), in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Although LMWH has superior efficacy to UFH in NSTE-ACS, it must also provide cost-effectiveness or net-cost savings before its wide use can be approved by healthcare payers. The drug-acquisition costs of LMWH are higher than those of UFH, but economic analyses should also consider the initial medical resource consumption and the downstream costs associated with failed treatment and subsequent care. Based on published economic analyses, the incremental drug costs of LMWH compared with UFH are compensated for by savings in medical-resource costs secondary to reducing ischemic events in NSTE-ACS patients.

Survey of hospitals for guidelines, policies, and protocols for anticoagulants.

PURPOSE: A survey of community hospitals that are part of a national group purchasing organization (GPO) was conducted to assess the formulary status of currently available anticoagulants, assess the current status of anticoagulant prescribing guidelines and the existing scope of such guidelines, and identify perceptions about the appropriateness of the use of anticoagulants in community hospitals in the United States. METHODS: A Web-based survey of acute care hospitals that were members of a leading health care resource management and GPO was conducted. The survey was sent to 224 hospitals. RESULTS: Of 224 hospitals, 127 participated in the survey, a response rate of 59.6%. Warfarin, unfractionated heparin (UFH), and enoxaparin were the anticoagulants most commonly included (>80%) on the hospitals' drug formularies. Guidelines relating to the use of UFH and low-molecular-weight heparins (LMWHs) existed in approximately 87.4% and 55.1% of responding hospitals, respectively, followed by warfarin and direct thrombin inhibitors (DTIs) (approximately 44.1% and 30.7%, respectively). Among hospitals without guidelines, 78.2%, 72.1%, 65.4%, 50.0%, and 41.4% reported that such guidelines would be useful if they included LMWHs, warfarin, DTIs, UFH, and fondaparinux, respectively. Guidelines for prophylaxis of venous thromboembolism (VTE), appropriate drug selection, and dosing for VTE prophylaxis and treatment existed in 59.8%, 53.5%, and 43.3% of the hospitals, respectively. CONCLUSION: The study found that a sizable percentage of the responding community hospitals did not have guidelines, protocols, or policies related to the use of anticoagulants. Further, those hospitals without such guidelines commonly reported a need for clinical practice guidelines.