Impact of an alcohol withdrawal screening and treatment protocol for hospitalized patients.

INTRODUCTION: Alcohol Withdrawal Syndrome (AWS) is a potentially life-threatening complication of alcohol use disorder (AUD) that can be challenging to recognize in hospitalized patients. Our institution implemented universal AUD screening for all patients admitted to a non-critical care venue using the Prediction of Alcohol Withdrawal Severity Scale (PAWSS). At risk patients were then further assessed, utilizing the Glasgow Modified Alcohol Withdrawal Scale (GMAWS), and medicated according to a predetermined protocol. This study sought to determine whether this protocol decreased hospital length of stay, lowered the total benzodiazepine dose administered, and decreased adverse events attributable to AWS. METHODS: This retrospective cohort study was conducted over a 6-year period from 2014 to 2020. The study included patients with an ICD-10 code diagnosis of AWS and subsequently divided them into two groups: pre- and post-protocol introduction. Outcome measures were compared pre- versus post-protocol introduction. RESULTS: There were 181 patient encounters pre- and 265 patient encounters post-protocol. There was no statistically significant difference in median length of stay between the two groups (2.956 days pre and 3.250 days post-protocol, p = 0.058). Post-protocol, there was a statistically significant reduction in median total benzodiazepine dose (13.5 mg and 9 mg lorazepam equivalents pre- and post-protocol, p < 0.001) and in occurrence of delirium tremens (7.7 % pre and 2.3 % post-protocol, p = 0.006). CONCLUSION: Protocol implementation did not reduce length of stay in patients with AUD but was associated with a significant reduction in total benzodiazepine dose and, when adjusted, a non-statistically significant decrease in progression to delirium tremens in hospitalized patients, after applying Bonferroni adjustment.

A Retrospective Cohort Study of Disparities in Urine Drug Testing During the Perinatal Period in an Urban, Academic Medical Center.

The purpose of this study was to evaluate disparities in urine drug testing (UDT) during perinatal care at a single academic medical center. This retrospective cohort study included patients who had a live birth and received prenatal care at our institution between 10/1/2015 and 9/30/2020. The primary outcomes were maternal UDT during pregnancy (UDTPN) and UDT only at delivery (UDTDEL). Secondary outcomes included the number of UDTs (UDTNUM) and the association between a positive UDT test result and race/ethnicity. Mixed model logistic regression and negative binomial regression with clustering based on prenatal care locations were used to control for confounders. Of 6,240 live births, 2,265 (36.3%) and 167 (2.7%) received UDTPN and UDTDEL, respectively. Black (OR 2.09, 95% CI 1.54-2.84) and individuals of Other races (OR 1.64, 95% CI 1.03-2.64) had greater odds of UDTPN compared to non-Hispanic White individuals. Black (beta = 1.12, p < 0.001) and Hispanic individuals (beta = 0.78, p < 0.001) also had a positive relationship with UDTNUM. Compared to individuals with non-Medicaid insurance, those insured by Medicaid had greater odds of UDTPN (OR 1.66, 95% CI 1.11-2.49) and had a positive relationship with UDTNUM (beta = 0.89, p < 0.001). No significant associations were found for UDTDEL and race/ethnicity. Despite receiving more UDT, Black individuals were not more likely to have a positive test result compared to non-Hispanic White individuals (OR 0.95, 95% CI 0.72-1.25). Our findings demonstrate persistent disparities in substance use testing during the perinatal period.

Evaluation of an injectable monthly extended-release buprenorphine program in a low-barrier specialty addiction medicine clinic.

INTRODUCTION: Monthly injectable extended-release buprenorphine (XR-BUP) can address several systemic and individual barriers to consistent sublingual buprenorphine treatment for patients with opioid use disorder (OUD). Real-world evaluations of XR-BUP in the outpatient addiction treatment setting are limited. The purpose of this study was to compare 6-month treatment retention and urine drug tests between patients who initiated XR-BUP compared to those who were prescribed but did not initiate XR-BUP in a low-barrier addiction medicine specialty clinic. METHODS: We conducted a retrospective cohort study of adults with OUD prescribed XR-BUP between 12/1/2018 and 12/31/2020 in a low-barrier addiction medicine specialty clinic to compare 6-month treatment retention between patients who initiated XR-BUP and those who were prescribed but did not initiate XR-BUP (comparison group). Secondary outcomes included percent of urine toxicology tests negative for non-prescribed opioids. Multivariable logistic regression models evaluated factors associated with 6-month treatment retention and XR-BUP initiation. RESULTS: Of the 233 patients prescribed XR-BUP, 148 (63.8 %) identified as non-Hispanic white, 218 (93.6 %) were insured by public insurance (Medicare/Medicaid), and nearly two-thirds were prescribed XR-BUP due to unstable OUD. Approximately 50 % of patients initiated XR-BUP treatment (mean number of injections = 3.7). About 60 % of XR-BUP-treated patients received supplemental sublingual buprenorphine and nearly two-thirds received a 300 mg maintenance dose. Six-month treatment retention was greater in the XR-BUP treatment versus comparison group (70.3 % vs. 36.5 %, p < 0.001). The XR-BUP treatment group had a higher percentage of opioid-negative urine toxicology tests versus the comparison group (67.2 % vs. 36.3 %, p < 0.001). Receipt of XR-BUP was an independent predictor of 6-month treatment retention (OR 5.40, 95 % CI 2.18-13.38). Those prescribed XR-BUP due to unstable OUD had lower odds of treatment retention (OR 0.41, 95 % CI 0.24-0.98) after controlling for receipt of XR-BUP and other variables known to impact retention. CONCLUSIONS: XR-BUP improved 6-month treatment retention and resulted in a greater proportion of opioid-negative urine toxicology tests compared to a comparison group of patients who were prescribed but did not initiate XR-BUP. Patients with unstable OUD had lower odds of XR-BUP initiation, suggesting the need for targeted interventions to increase XR-BUP uptake in this high-risk population.

Hospital-initiated Extended-release Injectable Buprenorphine Using a Novel Reallocation Initiative From an Outpatient Addiction Medicine Clinic.

OBJECTIVES: Novel strategies for initiation and continuation of buprenorphine are critical, especially during a pandemic when traditional opioid use disorder treatment pathways may be disrupted. We describe an innovative outpatient to inpatient reallocation initiative for extended-release buprenorphine (XR-BUP) designed to repurpose an expensive medication for use in hospitalized patients facing treatment barriers upon discharge and pilot the feasibility of XR-BUP use in the inpatient setting. METHODS: We collaborated with our institution's inpatient pharmacy and a New Jersey Medicaid managed care organization to create an alternate pathway to make XR-BUP available to hospitalized patients insured by the same payor. In this process, XR-BUP doses were deidentified and transferred to the inpatient controlled substance inventory for administration to hospitalized patients at no charge by our Addiction Medicine Consult Service after a period of sublingual buprenorphine stabilization. Our reallocation pathway bypassed several existing XR-BUP regulatory barriers to allow for inpatient administration. RESULTS: To date, we have transferred approximately 85 XR-BUP 300 mg doses to the inpatient controlled substance inventory. This equates to a cost savings of nearly $145,000. CONCLUSIONS: Reallocation of XR-BUP from an outpatient to inpatient setting increased postdischarge buprenorphine treatment access while also reducing health care costs by repurposing an expensive medication that would otherwise go to waste. Use of reallocated XR-BUP in the inpatient setting may pave the way for addition of XR-BUP to the hospital's formulary to minimize treatment gaps after discharge.

Attitudes on Methadone Utilization in the Emergency Department: A Physician Cross-sectional Study.

INTRODUCTION: Like buprenorphine, methadone is a life-saving medication that can be initiated in the emergency department (ED) to treat patients with an opioid use disorder (OUD). The purpose of this study was to better understand the attitudes of emergency physicians (EP) on offering methadone compared to buprenorphine to patients with OUD in the ED. METHODS: We distributed a perception survey to emergency physicians through a national professional network. RESULTS: In this study, the response rate was 18.4% (N = 141), with nearly 70% of the EPs having ordered either buprenorphine or methadone. 75% of EPs strongly or somewhat agreed that buprenorphine was an appropriate treatment for opioid withdrawal and craving, while only 28% agreed that methadone was an appropriate treatment. The perceived barriers to using buprenorphine and methadone in the ED were similar. CONCLUSION: It is essential to create interventions for EPs to overcome stigma and barriers to methadone initiation in the ED for patients with opioid use disorder. Doing so will offer additional opportunities and pathways for initiation of multiple effective medications for OUD in the ED. Subsequent outpatient treatment linkage may lead to improved treatment retention and decreased morbidity and mortality from ongoing use.

Availability of buprenorphine/naloxone films and naloxone nasal spray in community pharmacies in 11 U.S. states.

BACKGROUND: Prompt access to prescribed buprenorphine/naloxone films (BUP/NX) and naloxone nasal spray (NNS) is vital for patients with opioid use disorder (OUD), but multiple studies have documented pharmacy-level barriers. METHODS: A cross-sectional secret shopper telephone audit was conducted in a sample of 5734 actively licensed pharmacies in 11 U.S. states from May 2020-April 2021. Primary outcomes included availability of 14 generic BUP/NX 8/2 mg and one unit of NNS 4 mg. Outcomes were compared by pharmacy type, county metropolitan status, state Medicaid expansion status, and state drug overdose death rate. RESULTS: Data from 4984 pharmacies (3402 chain and 1582 independent) were analyzed. Both medications were available in 41.2 % of pharmacies, BUP/NX was available in 48.3%, and NNS was available in 69.5%. Chain pharmacies were significantly more likely than independent pharmacies to have both medications available, to have each medication available individually, and to be willing to order BUP/NX. Pharmacies in metropolitan counties were more likely to have BUP/NX available than pharmacies in non-metropolitan counties, pharmacies in Medicaid expansion states were more likely to have both medications available and to have NNS available than pharmacies in non-expansion states, and pharmacies in states with high drug overdose death rates were more likely to have NNS available than pharmacies in states with low drug overdose death rates. CONCLUSIONS: BUP/NX and NNS are not readily accessible in many U.S. pharmacies. Deficits in access are most pronounced in independent pharmacies, though county- and state-level factors may also influence availability of these essential medications.

Exploring Barriers and Facilitators to Glycemic Control and Shared Medical Appointment Engagement in Underserved Patients with Diabetes.

OBJECTIVE: The purpose of this study was to evaluate barriers and facilitators to glycemic control and diabetes shared medical appointment (SMA) engagement in underserved patients with type 2 diabetes. METHODS: Semi-structured focus groups were conducted in 50 patients using an interview script guided by a social determinants of health (SDOH) conceptual framework. RESULTS: Patients positively perceived the social support and access to care benefits of the SMA. While barriers related to self-care behaviors (particularly diet), financial issues, and unreliable transportation were common, notable differences among the four groups existed. Controlled patients were motivated by fear of diabetic complications. Poorly-controlled patients discussed comorbidities and negative influence of family as barriers to glycemic control. Diabetes distress and fatalism were endorsed by poorlycontrolled, non-engaged patients. CONCLUSIONS: Overcoming SDOH including transportation barriers, food insecurity, and diabetes distress and fatalism are promising areas of intervention for SMA models to improve care for underserved populations.

A Low-threshold Comprehensive Shared Medical Appointment Program for Perinatal Substance Use in an Underserved Population.

OBJECTIVES: We describe retention in care, medication for opioid use disorder (MOUD) prescribing, and urine toxicology outcomes of a comprehensive perinatal shared medical appointment model that combined medication, group-based counseling, and recovery supports. METHODS: We conducted a retrospective study of program retention between 11/1/16 and 3/31/20 in pregnant and postpartum women with substance dependence or use disorder. Disengagement reasons, MOUD prescribing, and urine toxicology were abstracted from medical records. A Cox proportional hazards model was used to evaluate risk factors for program disengagement. RESULTS: Approximately 87% of patients had OUD and 80% were pregnant at the initial visit (N = 140). Retention at 3 months, 6 months, 1 year, and 2 years was approximately 86%, 78%, 66%, and 48%, respectively. Over 97% of patients were prescribed MOUD and 88% of all urine toxicology results were negative for non-prescribed opioids. Patients enrolled after initiation of wraparound services (HR 0.52, 95% CI 0.28 - 0.96) and those attending more shared medical appointments (HR 0.90, 95% CI 0.87 - 0.93) had a lower hazard of disengagement after controlling for other covariates. Loss to follow-up was the most common disengagement reason. CONCLUSIONS: A low-threshold, comprehensive perinatal shared medical appointment program had high retention rates, increased access to evidence-based MOUD, and high rates of opioid-negative urine toxicology. Participants enrolled after wraparound services began had a lower hazard of disengagement. Future research in perinatal substance use should evaluate the most optimal and cost-effective components of comprehensive programs to inform standard of care.

Effect of Peer Mentors in Diabetes Self-management vs Usual Care on Outcomes in US Veterans With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: Diabetes is a substantial public health issue. Peer mentoring is a low-cost intervention for improving glycemic control in patients with diabetes. However, long-term effects of peer mentoring and creation of sustainable models are not well studied. Objective: Assess the effects of a peer support intervention for improving glycemic control in patients with diabetes and evaluate a model in which former mentees serve as mentors. Design, Setting, and Participants: A randomized clinical trial was conducted from September 27, 2012, to March 21, 2018, at the Corporal Michael J. Crescenz Medical Center. US veterans with type 2 diabetes aged 30 to 75 years with hemoglobin A1C (HbA1c) greater than 8% received support over 6 months from peers with prior poor glycemic control but who had achieved HbA1c less than or equal to 7.5% (phase 1). Phase 1 mentees were then randomized to become a mentor or not to new randomly assigned participants in phase 2. Outcomes were assessed at 6 and 12 months. Data were analyzed from October 5, 2016, to September 4, 2018. Interventions: Mentors who received an initial training session and monthly reinforcement training were assigned 1 mentee and given $20 for each month they contacted their mentee at least weekly. Main Outcomes and Measures: Primary outcome was HbA1c change at 6 months. Secondary outcomes included HbA1c change at 12 months and change in low-density lipoprotein, blood pressure, diabetes quality of life, and depression symptoms at 6 and 12 months. Results: The study enrolled 365 participants into phase 1 and 122 participants into phase 2. Most participants were Black (341 [66%]) and male (454 [96%]), with a mean (SD) age of 60 (7.5) years. Mean phase 1 HbA1c change at 6 months for usual care was -0.20% (95% CI, -0.46% to 0.06%) vs -0.52% (95% CI, -0.76% to -0.29%) for mentees (P = .06). Mean phase 2 HbA1c change at 6 months for usual care was -0.46% (95% CI, -1.02% to 0.10%) vs 0.08% (95% CI, -0.42% to 0.57%) for mentees (P = .16). There were no differences in secondary outcomes or HbA1c levels at 12 months. There was no benefit to past mentees who became mentors. Conclusions and Relevance: In this randomized clinical trial, a peer mentor intervention did not improve 6-month HbA1c levels and did not have sustained benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT01651117.

Impact of a Multidisciplinary, Endocrinologist-Led Shared Medical Appointment Model on Diabetes-Related Outcomes in an Underserved Population.

A multidisciplinary endocrinologist-led shared medical appointment (SMA) model showed statistically significant reductions in A1C from baseline over 3 years that were not significantly different from appointments with endocrinologists or primary care providers alone within a resource-poor population. Similarly, the SMA model achieved clinical outcomes on par with endocrinologist-only visits with the added benefit of improving endocrine provider productivity and specialty access for patients. Greater patient engagement with the SMA model was associated with significantly lower A1C.

Insights Into Veterans' Perspectives on a Peer Support Program for Glycemic Management.

PURPOSE: The purpose of this study was to explore the mentor-mentee relationship in veterans with type 2 diabetes and gain insight into successful pairings. METHODS: Qualitative semistructured interviews were conducted as part of a peer mentoring randomized controlled trial to understand participants' experiences, their relationship with their partner, and how the intervention affected self-care behaviors. Purposive sampling was done to ensure adequate representation of mentees who made large strides in reaching their glycemic targets, those who made marginal improvements toward their glycemic goals, and those who got worse. All interviews were audio-recorded, transcribed, and analyzed for salient themes. RESULTS: The intervention was well received, with most participants describing it as valuable. Participants perceived the intervention to have a number of benefits, including accessible support, enhanced self-confidence, increased accountability, better self-efficacy, improved glycemic management, and a fulfilled sense of altruism. Participants did encounter barriers, including logistical, interpersonal, and individual obstacles. The more successful mentees tended to be more effusive in their description of their mentors, endorsed a stronger sense of connection to their mentor, described a more structured interaction with their mentor, and tended to be more complimentary of the intervention. CONCLUSIONS: Large peer support programs are appealing and well received. These programs can be optimized by selecting naturally inclined mentors, providing additional training to introduce more structure into mentorship interactions, and targeting mentees who are not struggling with overwhelming comorbidities.

Pharmacy, physical therapy, occupational therapy, and physician assistant professional students' perspectives on interprofessional roles and responsibilities.

Understanding roles and responsibilities within the interprofessional practice is a key competency of interprofessional education (IPE). Students in health professions programs can have limited understanding and perceptions of health professions, including their own and other professions. The purpose of this study was to understand students' perceptions of the roles and responsibilities of other health-care professionals. Students enrolled in occupational therapy, pharmacy, physical therapy, and physician assistant programs at a university participated in a three-hour IPE workshop. Throughout this workshop, they worked in small interprofessional teams to identify unique and shared roles and responsibilities of health professions. Students used a "dream catcher" graphic organizer to compare and contrast these roles and responsibilities. Researchers used thematic analysis of completed graphic organizers to identify themes in students' perceptions. Students identified many shared and unique characteristics about their professions' values and expertise, patient care process, practice settings, patient populations, education, and regulations. While students correctly identified many aspects of their professions, there were some inaccuracies that were addressed by small group faculty facilitators.

A practical guide for pharmacists to establish a transitions of care program in an outpatient setting.

OBJECTIVES: To improve understanding of the logistics of transitions of care (TOC) clinics and to provide guidance to pharmacists in developing and implementing a new TOC clinic or improving an existing one. SETTING: Outpatient TOC clinic within an ambulatory care practice. PRACTICE DESCRIPTION: Two general internal medicine practices collaborated with a university health system to create an interdisciplinary TOC clinic to improve quality and continuity of patient care. The clinic accommodates any patients of the practice who are not able to get an appointment with their primary care physician within 1 to 2 weeks of discharge from any hospital. Physician residents, an attending physician, a clinical pharmacist, a nurse, medical assistants, and a social worker (if necessary) are involved in the patient's care during the transition process. PRACTICE INNOVATION: Pharmacists can play a vital role in developing and implementing a TOC clinic or enhancing a current one. There are many logistical components to consider in developing a clinic, and this article provides guidance in the various steps required in creating a clinic, including support and coordination, personnel, workflow, operations, reimbursement, marketing, metrics, and measures. CONCLUSION: This tool may help pharmacists implement or enhance an outpatient TOC clinic to improve patient care, quality, and continuity.

Pharmacists implementing transitions of care in inpatient, ambulatory and community practice settings.

OBJECTIVE: To introduce pharmacists to the process, challenges, and opportunities of creating transitions of care (TOC) models in the inpatient, ambulatory, and community practice settings. METHODS: TOC literature and resources were obtained through searching PubMed, Ovid, and GoogleScholar. The pharmacist clinicians, who are the authors in this manuscript are reporting their experiences in the development, implementation of, and practice within the TOC models. RESULTS: Pharmacists are an essential part of the multidisciplinary team and play a key role in providing care to patients as they move between health care settings or from a health care setting to home. Pharmacists can participate in many aspects of the inpatient, ambulatory care, and community pharmacy practice settings to implement and ensure optimal TOC processes. This article describes establishing the pharmacist's TOC role and practicing within multiple health care settings. In these models, pharmacists focus on medication reconciliation, discharge counseling, and optimization of medications [corrected]. CONCLUSION: Optimizing the TOC process, reducing medication errors, and preventing adverse events are important focus areas in the current health care system, as emphasized by The Joint Commission and other health care organizations. Pharmacists have the unique opportunity and skillset to develop and participate in TOC processes that will enhance medication safety and improve patient care.

Role of novel and emerging oral anticoagulants for secondary prevention of acute coronary syndromes.

Dual antiplatelet therapy has become a mainstay of long-term management of patients after an acute coronary syndrome (ACS). Mortality for these patients remains high despite current evidence-based treatment strategies. The coagulation cascade plays a role in the pathophysiology of ACS, and trials with warfarin in combination with dual antiplatelet therapy have found decreased rates of ischemic events at the expense of increased bleeding risk. Novel oral anticoagulants (NOACs) in the direct factor Xa (FXa) inhibitor and direct thrombin inhibitor (DTI) categories have been evaluated in combination with standard post-ACS therapy. Rivaroxaban, a FXa inhibitor, reduced the rates of ischemic events but increased major bleeding rates. Apixaban did not decrease the rates of ischemic events and also increased major bleeding rates. Other FXa inhibitors have not been studied in the long-term management of ACS (e.g., otamixaban), are not currently being studied in ongoing phase III trials (e.g., TAK-442), or have been discontinued by the manufacturer (e.g., darexaban). The DTI dabigatran had a 2- to 4-fold increased risk of major bleeding with unclear benefit for reducing ischemic events. The factor IXa inhibitor pegnivacogin is an RNA-based aptamer that has been studied in patients undergoing cardiac catheterization but has not been studied for long-term post-ACS management. The European Society of Cardiology Working Group on Thrombosis recommends the use of newer antiplatelet agents over addition of NOACs. Additional guidelines are available to guide management in patients requiring triple antithrombotic therapy but do not provide definitive recommendations on NOACs. Many questions remain about the place of NOACs for long-term post-ACS management. Recent trials have evaluated double versus triple antithrombotic therapy to balance efficacy and bleeding risk, but they did not include NOACs. It also remains unclear if NOACs hold a place in post-ACS therapy in the era of more potent antiplatelet agents such as prasugrel and ticagrelor.

Patterns of non-administration of ordered doses of venous thromboembolism prophylaxis: implications for novel intervention strategies.

BACKGROUND: Recent studies have documented high rates of non-administration of ordered venous thromboembolism (VTE) prophylaxis doses. Intervention strategies that target all patients have been effective, but prohibitively resource-intensive. We aimed to identify efficient intervention strategies based on patterns of non-administration of ordered VTE prophylaxis. METHODS AND FINDINGS: In this retrospective review of electronic medication administration records, we included adult hospitalized patients who were ordered pharmacologic VTE prophylaxis with unfractionated heparin or enoxaparin over a seven-month period. The primary measure was the proportion of ordered doses of VTE prophylaxis not administered, assessed at the patient, floor, and floor type levels. Differences in non-administration rates between groups were assessed using generalized estimating equations. A total of 103,160 ordered VTE prophylaxis doses during 10,516 patient visits on twenty-nine patient floors were analyzed. Overall, 11.9% of ordered doses were not administered. Approximately 19% of patients missed at least one quarter and 8% of patients missed over one half of ordered doses. There was marked heterogeneity in non-administration rate at the floor level (range: 5-27%). Patients on medicine floors missed a significantly larger proportion (18%) of ordered doses compared to patients on other floor types (8%, Odds Ratio: 2.4, p<0.0001). However, more than half of patients received at least 86% of their ordered doses, even on the lowest performing floor. The 20% of patients who missed at least two ordered doses accounted for 80% of all missed doses. CONCLUSIONS: A substantial proportion of ordered doses of VTE prophylaxis were not administered. The heterogeneity in non-administration rate between patients, floors, and floor types can be used to target interventions. The small proportion of patients that missed multiple ordered doses accounted for a large majority of non-administered doses. This recognition of the Pareto principle provides opportunity to efficiently target a relatively small group of patients for intervention.

Rivaroxaban: an oral factor Xa inhibitor.

BACKGROUND: Currently available anticoagulants utilized for venous thromboembolism (VTE) treatment and prevention and stroke prevention in patients with atrial fibrillation (AF) have proven effectiveness but are not optimally utilized because of barriers such as the need for subcutaneous administration and requisite routine laboratory monitoring. Rivaroxaban, a novel oral Xa inhibitor, is an alternative to standard therapies utilized for VTE prevention after elective orthopedic surgery, primary and secondary stroke prevention in nonvalvular AF, VTE treatment after an acute VTE event, and secondary prevention after the acute coronary syndromes (ACS). OBJECTIVE: This article reviews the pharmacology, efficacy, and tolerability of rivaroxaban for VTE prophylaxis in post-orthopedic surgery and medically ill patients, stroke prevention in nonvalvular AF, adjunctive therapy in patients with ACS, and VTE treatment. METHODS: International Pharmaceutical Abstracts and EMBASE were searched for English-only clinical trials and reviews published between 1970 and March 15, 2012. PubMed was searched for articles published between 1970 and June 30, 2012. Additional trials and reviews were identified from the citations of published articles. RESULTS: Eighty-nine publications were identified: 10 clinical trials and 1 meta-analysis were used to obtain efficacy and tolerability data, and 1 analysis of pooled data from the clinical trials was included; 17 pharmacokinetic, pharmacodynamic, and drug-drug interaction studies were included; and 5 cost-analyses were reviewed. These data showed rivaroxaban to be noninferior to enoxaparin for thromboprophylaxis of VTE after total knee and total hip replacement surgery. It was also shown to be noninferior to vitamin K antagonist therapy for primary and recurrent stroke prevention in nonvalvular AF as well as for the treatment of VTE after an acute deep vein thrombosis or pulmonary embolism. It also showed benefit in lowering the risk for major adverse cardiovascular events after ACS. Differences in major bleeding rates were not statistically significant between rivaroxaban and comparators across the various studies, with the exception of ACS, in which there were higher rates of non-coronary artery bypass graft surgery related bleeding and intracranial hemorrhage. CONCLUSIONS: Based on the findings of the studies reported in this review, rivaroxaban is an effective option for the prevention of VTE after orthopedic surgery, stroke prevention for nonvalvular AF, and treatment of VTE. At this time, rivaroxaban cannot be recommended for secondary risk reduction after ACS because of the increased bleeding risk.