Comparative outcomes associated with rivaroxaban versus warfarin use in elderly patients with atrial fibrillation or acute venous thromboembolism managed in the United States: a systematic review of observational studies.

BACKGROUND: Advancing age is a risk factor for developing non-valvular atrial fibrillation (NVAF) or acute venous thromboembolism (VTE). We assessed the comparative effectiveness, safety, costs, and healthcare utilization associated with rivaroxaban versus warfarin in patients of advanced age managed in the United States (US). METHODS: We conducted a systematic review of Medline and Embase through April 2023 to identify real-world evidence (RWE) studies of older adults (at least 65+ years of age) with either NVAF or VTE who received either rivaroxaban or warfarin in the US and reported an outcome of stroke or systemic embolism (SSE), ischemic stroke (IS), recurrent VTE, major bleeding, intracranial hemorrhage, costs, or healthcare resource utilization. We classified each outcome of interest per study as "positive" (lower risk), "negative" (higher risk), or "neutral" based upon the summary effect size of rivaroxaban versus warfarin. RESULTS: Twenty-nine RWE studies met inclusion criteria, mostly (83%) in NVAF populations. For SSE with rivaroxaban versus warfarin, 68.8% of studies showed positive effects and 31.2% showed neutral outcome. For major bleeding, 57.7% showed neutral effects, 38.5% showed negative effects, and 3.8% of studies showed positive effects with rivaroxaban versus warfarin. Of the two studies reporting cost data, both were positive, showing lower costs for SSE for rivaroxaban versus warfarin and neutral cost for major bleeding costs. CONCLUSIONS: This systematic review supports findings from subgroup analyses of randomized controlled trials that, compared with warfarin, rivaroxaban is associated with generally neutral or positive effects on thrombosis and a mixed picture on bleeding outcomes in older adults with either NVAF or VTE treated in the United States.

Weight and BMI Changes Following Initiation of Emtricitabine/Tenofovir Alafenamide Co-Formulated with Darunavir or Co-Administered with Dolutegravir in Overweight or Obese, ART-Naïve People Living with HIV-1.

Introduction: Integrase strand transfer inhibitor-based regimens (eg, containing dolutegravir [DTG]) are associated with weight/body mass index (BMI) increases among people living with HIV-1 (PLWH). Assessing antiretroviral therapy (ART)-related weight/BMI changes is challenging, as PLWH may experience return-to-health weight gain as a result of viral suppression. This retrospective, longitudinal real-world study compared weight/BMI outcomes among overweight/obese (BMI ≥25 kg/m2; thus excluding return-to-health weight/BMI changes), treatment-naïve PLWH who initiated darunavir (DRV)/cobicistat (c)/emtricitabine (FTC)/tenofovir alafenamide (TAF) or DTG + FTC/TAF. Methods: Treatment-naïve PLWH with BMI ≥25 kg/m2 who initiated DRV/c/FTC/TAF or DTG + FTC/TAF (index date) had ≥12 months of baseline observation and ≥1 weight/BMI measurement in baseline and post-index periods in the Symphony Health IDV® database (07/17/2017-12/31/2021) were included. Inverse probability of treatment weighting (IPTW) was used to balance differences in baseline characteristics between cohorts. On-treatment time-to-weight/BMI increases ≥5% were compared between cohorts using weighted adjusted Cox models. Results: Post-IPTW, 76 overweight/obese DRV/c/FTC/TAF-treated (mean age = 51.2 years, 30.7% female, 35.6% Black, mean baseline BMI = 33.2 kg/m2) and 88 overweight/obese DTG + FTC/TAF-treated PLWH (mean age = 51.5 years, 31.4% female, 31.4% Black, mean baseline BMI = 32.7 kg/m2) were included. The median [interquartile range] time from ART initiation to weight/BMI increase ≥5% was shorter for the DTG + FTC/TAF cohort (21.8 [9.9, 32.3] months) than the DRV/c/FTC/TAF cohort (median and interquartile times not reached; Kaplan-Meier rate at 21.8 months = 20.8%). Over the entire follow-up, overweight/obese PLWH initiating DTG + FTC/TAF had a more than twofold greater risk of experiencing weight/BMI increase ≥5% compared to those initiating DRV/c/FTC/TAF (hazard ratio [95% confidence interval]=2.43 [1.02; 7.04]; p = 0.036). Conclusion: Overweight/obese PLWH who initiated DTG + FTC/TAF had significantly greater risk of weight/BMI increase ≥5% compared to similar PLWH who initiated DRV/c/FTC/TAF and had shorter time-to-weight/BMI increase ≥5%, suggesting a need for additional monitoring to assess the risk of weight gain-related cardiometabolic disease.

Incidence of cardiometabolic outcomes among people living with HIV-1 initiated on integrase strand transfer inhibitor versus non-integrase strand transfer inhibitor antiretroviral therapies: a retrospective analysis of insurance claims in the United States.

INTRODUCTION: Integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART) has been associated with weight gain, though there is limited information on associations between ART-related weight gain and cardiometabolic outcomes among people living with HIV-1 (PLWH). We, therefore, evaluated risks of incident cardiometabolic outcomes following INSTI versus non-INSTI-based ART initiation in the United States. METHODS: We conducted a retrospective study using IBM MarketScan Research Databases (12 August 2012-31 January 2021). Treatment-naïve PLWH initiating ART (index date) on/after 12 August 2013 (approval date of the first second-generation INSTI, dolutegravir) were included and censored at regimen switch/discontinuation, end of insurance eligibility or end of data availability. We used inverse probability of treatment weights constructed with baseline (12 months pre-index) characteristics to account for differences between INSTI- and non-INSTI-initiating cohorts. Doubly robust hazard ratios (HRs) obtained from weighted multivariable Cox regression were used to compare time to incident cardiometabolic outcomes (congestive heart failure [CHF], coronary artery disease, myocardial infarction, stroke/transient ischemic attack, hypertension, type II diabetes, lipid disorders, lipodystrophy and metabolic syndrome) by INSTI-initiation status. RESULTS: Weighted INSTI (mean age = 39 years, 23% female, 70% commercially insured, 30% Medicaid insured) and non-INSTI (mean age = 39 years, 24% female, 71% commercially insured, 29% Medicaid insured) cohorts included 7059 and 7017 PLWH, respectively. The most common INSTI-containing regimens were elvitegravir-based (43.4%), dolutegravir-based (33.3%) and bictegravir-based (18.4%); the most common non-INSTI-containing regimens were darunavir-based (31.5%), rilpivirine-based (30.4%) and efavirenz-based (28.3%). Mean±standard deviation follow-up periods were 1.5±1.5 and 1.1±1.2 years in INSTI- and non-INSTI-initiating cohorts, respectively. INSTI initiators were at a clinically and significantly increased risk of experiencing incident CHF (HR = 2.12, 95% confidence interval [CI] = 1.08-4.05; p = 0.036), myocardial infarction (HR = 1.79, 95% CI = 1.03-5.65; p = 0.036) and lipid disorders (HR = 1.26, 95% CI = 1.04-1.58; p = 0.020); there was no evidence of an increased risk for other individual or composite outcomes. CONCLUSIONS: Over a short average follow-up period of <2 years, INSTI use among treatment-naïve PLWH was associated with an increased risk of several cardiometabolic outcomes, such as CHF, myocardial infarction and lipid disorders, compared to non-INSTI use. Further research accounting for additional potential confounders and with longer follow-up is warranted to more accurately and precisely quantify the impact of INSTI-containing ART on long-term cardiometabolic outcomes.

Effectiveness and Safety of Rivaroxaban Versus Warfarin among Nonvalvular Atrial Fibrillation Patients with Concomitant Obstructive Sleep Apnea.

Background Obstructive sleep apnea (OSA) is associated with an increased incidence of atrial fibrillation (AF), hypertension, diabetes, heart failure, coronary heart disease, stroke, and death. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular AF (NVAF) patients with concomitant OSA. Methods This was an analysis of electronic health record (EHR) data from November 2010 to December 2021. We included adults with NVAF and OSA at baseline, newly initiated on rivaroxaban or warfarin, and with ≥12 months of prior EHR activity. Patients with valvular disease, alternative indications for oral anticoagulation, or who were pregnant were excluded. The incidence rates of developing stroke or systemic embolism (SSE) and bleeding-related hospitalization were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using propensity score-overlap weighted proportional hazards regression. Multiple sensitivity and subgroup analyses were performed. Results We included 21,940 rivaroxaban (20.1% at the 15 mg dose) and 38,213 warfarin (time-in-therapeutic range = 47.3 ± 28.3%) patients. Rivaroxaban was found to have similar hazard of SSE compared to warfarin (HR = 0.92, 95% CI = 0.82-1.03). Rivaroxaban was associated with a reduced rate of bleeding-related hospitalizations (HR = 0.85, 95% CI = 0.78-0.92) versus warfarin, as well as reductions in intracranial (HR = 0.76, 95% CI = 0.62-0.94) and extracranial (HR = 0.89, 95%CI = 0.81-0.97) bleeding. Upon sensitivity analysis restricting the population to men with a CHA 2 DS 2 VASc score ≥2 or women with a score ≥3, rivaroxaban was associated with a significant 33% risk reduction in SSE and 43% reduction in the risk of bleeding-related hospitalization. No significant interaction for the SSE or bleeding-related hospitalization outcomes was observed upon subgroup analyses. Conclusion Among patients with NVAF and OSA, rivaroxaban had similar SSE risk versus warfarin but was associated with reductions in any intracranial and extracranial bleeding-related hospitalizations. Rivaroxaban was associated with significant reductions in SSE and bleeding-related hospitalizations when the study population was restricted to patients with a moderate-to-high risk of SSE. These data should provide prescribers with additional confidence in selecting rivaroxaban in NVAF patients who have OSA at the time of anticoagulation initiation.

Real-world weight changes in people with HIV-1 at risk of weight gain (female, Black or Hispanic) switching from integrase strand transfer inhibitors.

Aim: Compare weight changes between people living with HIV-1 (PLWH) at high risk of weight gain (females, Blacks or Hispanics) switching from an integrase strand transfer inhibitor (INSTI) to a protease inhibitor (PI) or another INSTI. Materials & methods: Mean weight changes from pre-switch to up-to-12 months post-switch were retrospectively compared between PLWH switching to a PI or INSTI. Results: 356 PLWH were eligible. At 9- and 12-month post-switch, weight increases were observed for INSTI (weight: +1.55 kg and +1.59 kg), while decreases were observed for PI (-0.23 kg and -1.59 kg); differences between cohorts widened over time. Conclusion: These data suggest that switching off an INSTI may be a management tool to mitigate or reverse weight gain.

Association Between Weight Gain and the Incidence of Cardiometabolic Conditions Among People Living with HIV-1 at High Risk of Weight Gain Initiated on Antiretroviral Therapy.

INTRODUCTION: Antiretroviral therapy (ART) has been associated with weight gain in people living with HIV-1 (PLWH); however, limited research has assessed whether early weight gain post-ART initiation is associated with metabolic or cardiovascular outcomes among PLWH at high risk of weight gain (i.e., female, Black or Hispanic). This study aimed to evaluate the incidence of metabolic and cardiovascular outcomes between PLWH at high risk of weight gain following an observed ≥ 5% or < 5% weight/body mass index (BMI) gain within 6 months following ART initiation. METHODS: A retrospective longitudinal study using Symphony Health, an ICON plc Company, IDV® electronic medical records (October 1, 2014-March 31, 2021) identified adult female, Black, or Hispanic treatment-naïve PLWH who initiated ART and who had ≥ 1 weight or BMI measurement pre- and within 6 months post-treatment (landmark period). Inverse probability of treatment weighting was used to account for differences between PLWH who experienced ≥ 5% and < 5% weight/BMI gain. The time to each outcome was compared between cohorts using weighted hazard ratios (HRs) after the landmark period. RESULTS: Weighted ≥ 5% and < 5% cohorts included 620 and 632 patients, respectively; baseline characteristics were similar between the two cohorts (mean age: ~ 48 years, ~ 59% female, ~ 49% Black, ~ 17% Hispanic). During a mean 2-year follow-up, PLWH with ≥ 5% weight/BMI gain were significantly more likely to be diagnosed with type 2 diabetes mellitus (T2DM; HR = 2.19; p = 0.044). There were no significant differences in the incidence of any other outcomes between the study cohorts. CONCLUSION: Despite a short 2-year follow-up, female, Black or Hispanic PLWH experiencing ≥ 5% weight/BMI increase within 6 months following ART initiation had an increased risk of T2DM, but not other metabolic or cardiovascular outcomes, likely due to the short follow-up period. Further research with longer follow-up and specific ART regimens is warranted to examine the impact of ART-related weight gain on long-term clinical outcomes.

Healthcare costs of NVAF patients treated with rivaroxaban and apixaban in the US.

OBJECTIVES: To provide the most current assessment of real-world healthcare resource utilization (HRU) and costs among patients with non-valvular atrial fibrillation (NVAF) who newly initiated rivaroxaban and apixaban using a large US database. MATERIAL AND METHODS: A retrospective weighted cohort design was used with healthcare insurance claims from the Optum Clinformatics Data Mart databases (January 2012-December 2018). The index date was defined as the first dispensing of rivaroxaban or apixaban. Adult NVAF patients with an index date on or after 1 January 2016, ≥ 12 months of continuous eligibility before the index date and ≥ 1 month after, and without prior use of oral anticoagulant were included. The observation period spanned from the index date to the earliest of the end of data availability, end of insurance coverage, or death. Inverse probability of treatment weighting (IPTW) was used to adjust for differences in baseline characteristics between cohorts. All-cause healthcare resource utilization (HRU), including hospitalization, emergency room, and outpatient visits, and healthcare costs, including medical and pharmacy costs, were evaluated from the payer's perspective during the observation period up to 18 and 24 months, separately. RESULTS: In total, 23,822 rivaroxaban and 53,666 apixaban users were included. After weighting, all baseline characteristics were well balanced between cohorts (mean age: 73.8 years, female: 46.6% in both cohorts). Up to 18 months of follow-up, rivaroxaban users incurred significantly lower total healthcare costs compared to apixaban users (cost difference = -$1,121; p = 0.020), driven by significantly lower rates of outpatient hospital visits and associated costs (cost difference = -$1,579; p < 0.001). Similar results were found in the analysis conducted for up to 24 months of follow-up (total cost difference = ‒$1,111; p = 0.020). CONCLUSIONS: In this large retrospective analysis, patients with NVAF initiated on rivaroxaban incurred significantly lower healthcare costs compared to those initiated on apixaban, which were primarily driven by significantly lower outpatient visits and costs during the 18- and 24-month follow-up periods.

The impact of non-medical switching among ambulatory patients: an updated systematic literature review.

Background: Non-medical switching (NMS) is defined as switching to a clinically similar but chemically distinct medication for reasons apart from lack of effectiveness, tolerability or adherence. Objective: To update a prior systematic review evaluating the impact of NMS on outcomes. Data sources: An updated search through 10/1/2018 in Medline and Web of Science was performed. Study selection: We included studies evaluating ≥25 patients and measuring the impact of NMS of drugs on ≥1 endpoint. Data extraction: The direction of association between NMS and endpoints was classified as negative, positive or neutral. Data synthesis: Thirty-eight studies contributed 154 endpoints. The direction of association was negative (n = 48; 31.2%) or neutral (n = 91; 59.1%) more often than it was positive (n = 15; 9.7%). Stratified by endpoint type, NMS was associated with a negative impact on clinical, economic, health-care utilization and medication-taking behavior in 26.9%,41.7%,30.3% and 75.0% of cases; with a positive effect seen in 3.0% (resource utilization) to 14.0% (clinical) of endpoints. Of the 92 endpoints from studies performed by the entity dictating the NMS, 88.0%were neutral or positive; whereas, only 40.3%of endpoints from studies conducted separately from the interested entity were neutral or positive. Conclusions: NMS was commonly associated with negative or neutral endpoints and was seldom associated with positive ones.

Real-world impact of glycated hemoglobin reduction on treatment intensification and glycated hemoglobin goal attainment in type 2 diabetes mellitus patients initiated on a sodium glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i).

Objective: To evaluate the impact of a 0.2% reduction in glycated hemoglobin (HbA1c) on treatment intensification, poor HbA1c control and HbA1c goal attainment in patients with type 2 diabetes mellitus (T2DM) initiated on a sodium glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i).Methods: IQVIATM Health Plan Claims Data - US and IQVIATM Ambulatory EMR Data - US databases (29 October 2012-31 March 2016) were used to identify adults with T2DM initiated on an SGLT2i (index date) who had HbA1c measurements pre- and post-index, and ≥6 months of eligibility pre-index (baseline). HbA1c change was defined as the difference between the first post-index and the last pre-index measurements. Cox regression models were used to assess treatment intensification, poor HbA1c control (i.e. HbA1c > 9%, among patients <9% at baseline) and goal attainment (HbA1c < 7%, <8%; among patients with HbA1c above goal at baseline) adjusting for HbA1c change and baseline characteristics. Patients were observed up to one year after the first HbA1c measurement or end of eligibility. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported.Results: A total of 938 patients (mean age 54.9, 42.5% female, mean HbA1c 8.5%) were selected. Following SGLT2i initiation, each 0.2% reduction in HbA1c levels was associated with a decreased risk of treatment intensification (HR [95% CI] = 0.90 [0.86-0.92]), a decreased likelihood of reaching HbA1c > 9% (HR [95% CI] = 0.85 [0.79-0.88]) and higher likelihoods of achieving a treatment goal of HbA1c < 7% (HR [95% CI] = 1.17 [1.12-1.21]) and HbA1c < 8% (HR [95% CI] = 1.08 [1.04-1.10]).Conclusions: In T2DM patients, each HbA1c reduction of 0.2% following the initiation of an SGLT2i was associated with a significant positive impact on treatment intensification and HbA1c goal attainment.

Policy Change for Deep Vein Thrombosis: Effects on Length of Stay and Hospitalization Costs of Moving From Warfarin to Direct Oral Anticoagulants.

PURPOSE: Renown Health (Reno, Nevada), a large, locally owned, not-for-profit integrated health care network, has developed an institution-wide policy to shift the treatment of deep vein thrombosis (DVT) from a short-acting anticoagulant and vitamin K antagonist to the direct oral anticoagulant rivaroxaban combined with pharmacy-directed follow-up at an outpatient anticoagulation clinic. We examined data on hospitalizations and costs pre-/post-policy change. METHODS: Data were obtained from the electronic health records of adults with newly diagnosed DVT treated at Renown Health. A quasi-experimental design was used to evaluate patients who received a DVT diagnosis before versus after the policy change. Primary outcomes were number of all-cause inpatient nights at 30 and 60 days post-DVT index date. Secondary outcomes were costs of all-cause overnight stays at 30 and 60 days post-DVT index. Outcomes were evaluated in propensity-weighted logistic regression and generalized linear models. FINDINGS: There were 343 patients pre-policy change and 266 post-policy change. In the first 30 days postindex, the mean (95% CI) numbers of propensity-weighted all-cause inpatient nights were 1.27 (0.83-1.95) prechange and 0.66 (0.42-1.02) postchange (P = 0.038). Mean propensity-weighted estimated all-cause hospital costs in patients diagnosed as outpatients were $7848 ($4990-$12,344) prechange and $2466 ($1553-$3915) postchange (P <0.001). Mean costs of all-cause overnight stays in inpatient-diagnosed DVT patients were $8907 prechange and $7449 postchange (P = 0.600). In the first 60 days postindex, the mean number of all-cause inpatient nights (P = 0.219) and mean costs of all-cause overnight stays (P = 0.275) were not significantly different before and after the policy change. IMPLICATIONS: Changing institutional policy to increase the utilization of a direct oral anticoagulant and pharmacist-led outpatient anticoagulation clinics may reduce length of hospital stay and decrease health care expenditures in the treatment of DVT.

Novel Type 2 Diabetes Medication Access and Effect of Patient Cost Sharing.

BACKGROUND: Although drug formulary restrictions may reduce use of prescription medication and pharmacy costs, the effect of patient cost sharing on medication adherence and health care utilization and cost is unclear. OBJECTIVE: To evaluate the relationship between patient cost sharing for novel type 2 diabetes mellitus (T2DM) medications and medication adherence, persistence, and health care utilization and cost. METHODS: This retrospective study used medical and pharmacy claims linked to pharmacy benefit plan design data. Patients with T2DM were identified via ICD-9-CM codes (medical claims), outpatient prescription fills (pharmacy claims), and pharmacy benefit design information. Patients with T2DM treated with novel T2DM medications (DPP4 or GLP-1) were enrolled in plans with fixed or coinsurance medication copayment structures and followed for 12-48 months. Endpoints included medication persistence and adherence and total all-cause health care cost. Multivariable regression analysis estimated the effect of benefit design parameters, adjusting for baseline patient characteristics. RESULTS: The integrated database included 36,475 patients with T2DM. The majority (83.1%) had fixed copayment plans, and 3-tier plans were common (93.1%). Higher third-tier copayment was associated with poorer medication adherence and persistence but not total health care cost during follow-up. A $10 higher third-tier copayment was associated with 11% greater risk of novel T2DM medication discontinuation and 3% lower adherence. A comparison of patients with fixed versus coinsurance plans found that fixed plans were associated with higher adjusted persistence and total all-cause health care costs. CONCLUSIONS: Higher medication copayment amounts were associated with lower patient medication adherence and persistence in T2DM but not total health care costs, as health plan costs decreased while patient out-of-pocket costs increased. We observed higher total all-cause health care costs among T2DM patients with a fixed copay (vs. coinsurance) pharmacy benefit. Additional research incorporating plan design information is needed to further examine this finding. DISCLOSURES: This study was funded by Janssen Scientific Affairs, which was involved in study design, interpretation of data, editing manuscript content, and had final approval of the manuscript before submission. Lopez and Bookhart are employed by Janssen Scientific Affairs. At the time of this study, Henk was employed by Optum HEOR, which was contracted by Janssen to conduct this study. Portions of this study were presented at the 21st Annual International Meeting, ISPOR; May 21-25, 2016; in Washington, DC.

Consequences of non-medical switch among patients with type 2 diabetes.

OBJECTIVE: This study aimed to describe real-world experiences following a non-medical switch among adults with type 2 diabetes mellitus (T2DM) in the United States. METHODS: For this cross-sectional study, patients with T2DM (N = 451) provided data on demographics, and how a non-medical switch of their anti-hyperglycemic agent (AHA) affected their general health, HbA1c levels and medication management, via an Internet-based survey. Patients self-reported their level of satisfaction with the original medication and emotional reactions to the non-medical switch. Patients who recently experienced a non-medical switch of their AHA(s) (n = 379) were asked about the consequences of switching and their satisfaction with the switch (vs. the original) medication. RESULTS: Patients most frequently reported feeling very/extremely frustrated, surprised, upset and angry in reaction to a non-medical switch. Patients were somewhat satisfied with their original medication. Between 20% and 30% of patients reported the non-medical switch had a moderate/major effect on their general health, diabetes, mental well-being and control over their health. The blood glucose levels of recent switchers were somewhat/much worse (20.7%) and medication management was somewhat/much worse (12.9%) on the switch (vs. the original) medication. Some recent switchers reported old symptoms returning (7.7%) and experiencing new side-effects (14.2%). CONCLUSIONS: Approximately one in five patients reported a moderate/major negative impact on their blood glucose level, diabetes, mental well-being, general health and control over their health following a non-medical switch. Findings suggest that a non-medical switch may have unintended negative health consequences and results in considerable burden across multiple domains for a sizeable minority of patients with T2DM.

Hospitalizations and Other Health Care Resource Utilization Among Patients with Deep Vein Thrombosis Treated with Rivaroxaban Versus Low-molecular-weight Heparin and Warfarin in the Outpatient Setting.

PURPOSE: Compared with low-molecular-weight heparin (LMWH) and warfarin, the oral anticoagulant rivaroxaban has advantages, such as simplified care, that may lead to less health care resource utilization. METHODS: A retrospective, matched-cohort analysis was conducted using claims dated between January 2011 and December 2013 from the Truven Health Analytics MarketScan databases. Adult patients who had a primary diagnosis of deep vein thrombosis (DVT) during an outpatient or emergency room (ER) visit after November 2, 2012, and who were treated with rivaroxaban or LMWH/warfarin on the same day, were identified. Patients were observed over 1, 2, 3, and 4 weeks after the DVT diagnosis. The mean numbers of hospitalizations for all causes and for venous thromboembolism (VTE) (which included those for DVT or pulmonary embolism), as well as other health care resource utilization (ER, outpatient, and other visits), and the associated health care costs and pharmacy costs, were evaluated and compared between cohorts using the Lin method. FINDINGS: All of the 512 rivaroxaban-treated patients were well matched with the LMWH/warfarin-treated patients. The mean numbers of all-cause hospitalizations were significantly lower in the rivaroxaban users compared with those in the LMWH/warfarin users over 1 week (0.012 vs 0.032; P = 0.044) and 2 weeks (0.022 vs 0.048; P = 0.040). The corresponding mean numbers of VTE-related hospitalizations were significantly lower with rivaroxaban over 1 week (0.008 vs 0.028; P = 0.020), 2 weeks (0.016 vs 0.042; P = 0.020), and 4 weeks (0.034 vs 0.068; P = 0.036). The mean numbers of all-cause and VTE-related outpatient visits were also significantly lower in rivaroxaban users compared with those in LMWH/warfarin users over 1, 2, 3, and 4 weeks (all, P < 0.001). In terms of all-cause and VTE-related ER and other visits, no statistically significant differences were found between cohorts over the first 4 weeks. The associated mean all-cause total health care costs were significantly lower in the rivaroxaban users compared with those in the LMWH/warfarin users over 1 week (US $2332 vs $3428; P < 0.001) and 2 weeks ($3108 vs $4524; P < 0.001); moreover, significantly lower mean costs related to all-cause hospitalizations (weeks 1 and 2) and pharmacy (weeks 1-4) were observed in patients treated with rivaroxaban, while no differences were found in costs related to ER visits (weeks 1-4), outpatient visits (weeks 1-4), or other visits (with the exception of week 1). IMPLICATIONS: Patients with DVT treated with rivaroxaban after an outpatient/ER visit had significantly lower mean numbers of hospitalizations and outpatient visits, as well as lower mean total, hospitalization, and pharmacy costs during the first 2 weeks of treatment compared with those in matched LMWH/warfarin users.

Quality measures for anticoagulation care.

OBJECTIVE: To systematically identify and assess current quality measures for anticoagulation in atrial fibrillation (AF), venous thromboembolism (VTE) treatment and surgical VTE prophylaxis. RESEARCH DESIGN AND METHODS: Fifteen quality measure websites were searched as were bibliographic databases (January 2000-February 2016). Quality measures were included if developed in the United States and incorporating an aspect of anticoagulation for the aforementioned indications or if applicable but not indication specific (non-disease specific measure). Two reviewers independently extracted data regarding the characteristics of each quality measure. RESULTS: Thirty-five measures were identified, mostly in VTE treatment (48.6%), followed by non-disease specific measures (25.7%), AF (17.6%) and surgical VTE prophylaxis (8.8%). Process measures predominated (82.9%). A majority of quality measures (65.7%) were focused on parenteral anticoagulants or warfarin and not applicable to novel oral anticoagulants (NOACs). Ten (28.6%) measures are used by the Centers for Medicare and Medicaid Services or as a core measure of The Joint Commission. Limitations include the inability to statistically pool data and possible publication bias given the nature of databases for quality measures. CONCLUSIONS: Quality measures are recognized in anticoagulation care. Areas for improvement include expanding beyond process measures and capturing adverse events and the advantages offered by NOACs.

Impact of non-medical switching on clinical and economic outcomes, resource utilization and medication-taking behavior: a systematic literature review.

OBJECTIVE: To evaluate current knowledge of the impact of non-medical switching on clinical and economic outcomes, resource utilization and medication-taking behavior. METHODS: The literature was searched (Medline and Web of Science, January 2000-November 2015) to identify United States' studies evaluating ≥25 patients and measuring the impact of non-medical switching of drugs (switching to a chemically distinct but similar medication for reasons other than lack of clinical efficacy/response, side effects or poor adherence) on ≥1 clinical, economic, resource utilization or medication-taking behavior outcome. The direction of association between non-medical switching and outcomes was classified as negative or positive if a statistically significant worsening or improvement was reported, or neutral if no significant difference was observed. RESULTS: Twenty-nine studies contributed 96 outcomes (60.4% clinical; 21.9% resource utilization; 13.5% economic; 4.2% medication-taking behavior) within six disease categories (cardio-metabolic, immune-mediated, acid suppression, psychiatric, hormone replacement therapy and pain). The direction of association was more frequently negative (33.3%) or neutral (55.2%) than it was positive (11.5%). Stratified by outcome type, non-medical switching was negatively associated with clinical, economic, healthcare utilization and medication-taking behavior outcomes in 20.7%, 69.2%, 38.1% and 75.0% of cases, respectively; and positively in only 4.8%-17.2% of outcomes subgroups. Of 32 outcomes in patients demonstrating stable/well controlled disease, 68.8% and 31.3% had a negative and neutral direction of association. In patients without demonstrated disease stability, outcomes were negatively, neutrally and positively impacted by non-medical switching in 15.6%, 67.2% and 17.2% of 64 outcomes. LIMITATIONS: Our inability to evaluate specific disease state categories and studies/outcomes received equal weight regardless of sample size or magnitude of effect. CONCLUSIONS: Non-medical switching was more often associated with negative or neutral effects than positive effects on an array of important outcomes. Among patients with stable/well controlled disease, non-medical switching was associated with mostly negative effects.

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.

Recurrent hospitalization and healthcare resource use among patients with deep vein thrombosis and pulmonary embolism: findings from a multi-payer analysis.

The objective of this study was to assess deep vein thrombosis and pulmonary embolism (DVT/PE) recurrence rates and resource utilization among patients with an initial DVT or PE event across multiple payer perspectives. Retrospective analyses were performed using a software tool that analyzes health plan claims to evaluate treatment patterns and resource utilization for various cardiovascular conditions. Six databases were analyzed from three payer perspectives (Commercial, Medicare, and Medicaid). Patients were ≥18 years old with a primary diagnosis of DVT or PE associated with an inpatient and/or emergency room claim, had received an antithrombotic within 7 days before or 14 days after index, and had no diagnosis of atrial fibrillation during follow-up. Outcomes were assessed over a 1 year period following index. More PE patients were hospitalized for their index event than DVT patients (42-59 % DVT and 69-86 % PE) and had longer mean length of stay (2.35-2.95 days DVT and 3.26-3.76 days PE). Recurrent event rates among PE patients (12-32 %) were higher than those for DVT patients (6-16 %) across all payers. The highest rate of recurrence was observed among the Medicaid population [23 % overall (VTE); 16 % DVT; 32 % PE]. All-cause hospitalization in the year following their VTE episode occurred in 23-67 % DVT patients and 30-68 % PE patients. Medicaid had the highest proportion of patients with hospitalizations and ER visits. Recurrent VTE events and all-cause hospitalizations are relatively common, especially for patients who had a PE, and among those in the Medicaid payer population.

Risk of recurrent venous thromboembolism among deep vein thrombosis and pulmonary embolism patients treated with warfarin.

OBJECTIVE: Guidelines for warfarin treatment of venous thromboembolism (VTE) recommend targeting an international normalized ratio (INR) level of 2-3. This study examines the association between INR levels and VTE recurrence among warfarin-treated patients. METHODS: A retrospective cohort study in the MedMining electronic health record database included adults treated with warfarin for VTE in 2004-2011. INR levels during warfarin use were categorized as below therapeutic range (<2), in range (2-3), or above range (>3), with time in each category estimated using the Rosendaal method. Recurrent VTE was noted from 30 days after the initial VTE to end of follow-up, which ranged up to 8 years. The incidence of recurrent VTE was calculated, and association with time-varying INR levels estimated using Cox models. RESULTS: Of 1753 qualifying patients, 867 had deep vein thrombosis, and 886 had pulmonary embolism. Mean age was 58 years, and 50.7% were female. Across all follow-up time, VTE recurrences were observed in 134 (7.6%) patients, at a rate of 3.2 (95% confidence interval [CI]: 0.7-9.1) events per 100 person-years. The risk of VTE recurrence was greater during time spent with INR <2 than with INR in the therapeutic range (hazard ratio [HR]: 3.37; 95% CI: 2.16-5.27). Low platelet counts also predicted greater risk of VTE recurrence (HR: 2.13; 95% CI: 1.24-3.67). LIMITATIONS: Exposure to warfarin and other anticoagulants was estimated based on prescription data and may be inaccurate. The study data include care within a single health system; thus, care received outside of the health system may be missing, and results may not be generalizable to the broader US population. CONCLUSIONS: Approximately 8% of patients experienced a recurrent VTE during follow-up. Subtherapeutic INR levels were associated with a more than three-fold increased risk of VTE recurrence.

Inpatient resource use and cost burden of deep vein thrombosis and pulmonary embolism in the United States.

PURPOSE: Venous thromboembolism (VTE), which comprises deep vein thrombosis (DVT) and pulmonary embolism (PE), is associated with significant morbidity and mortality. VTE frequently leads to hospitalization and represents a considerable economic burden to the US health care system. However, little information exists on the duration of hospitalization and associated charges among patients with an admitting or primary diagnosis of DVT or PE. This study assessed the charges associated with hospitalization length of stay in patients with DVT or PE discharged from US hospitals in 2011. METHODS: Using data from the Nationwide Inpatient Sample of the Healthcare Utilization Project database, this analysis examined hospital length of stay and associated charges in patients with DVT or PE discharged from US hospitals in 2011. Both initial and subsequent hospitalizations were analyzed. FINDINGS: DVT was responsible for fewer hospitalizations than PE. In 2011, among 330,044 patients with VTE discharged from US hospitals, 143,417 had DVT and 186,627 had PE. Mean length of stay for patients with DVT was 4.7 days (median, 3.9 days) compared with 5.1 days (median, 4.5 days) for patients with PE. For initial hospitalizations, the mean (SE) charge amounted to $30,051 ($246) for DVT compared with $37,006 ($214) for PE. Older patients with PE incurred greater hospital charges than younger ones, and for both DVT and PE patients, women incurred greater charges than men. Of 31,463 patients admitted to the hospital with PE, 4.0% had a subsequent admission, which was more costly than the initial admission. Many patients with both DVT and PE were discharged to specialist nursing facilities, indicating continuing posthospitalization charges. IMPLICATIONS: Hospital stays for DVT and PE represent a substantial cost burden to the US health care system. Health care systems have the potential to reduce the clinical and economic burden of VTE by ensuring that evidence-based, guideline-recommended anticoagulation therapy is adhered to by patients with an initial VTE. Appropriate anticoagulant therapy and continuity of care in these patients may reduce the incidence and frequency of hospital readmissions and VTE-related morbidity and mortality and have a potential effect on health care resources.