Real-World Impact of Blood Pressure Control in Patients With Apparent Treatment-Resistant or Difficult-to-Control Hypertension and Stages 3 and 4 Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is a common comorbidity in patients with apparent treatment-resistant hypertension (aTRH). We assessed clinical outcomes, healthcare resource utilization events, and costs in patients with aTRH or difficult-to-control hypertension and stage 3-4 CKD with uncontrolled vs. controlled BP. METHODS: This retrospective cohort study used linked IQVIA Ambulatory EMR-US and IQVIA PharMetrics Plus claims databases. Adult patients had claims for ≥3 antihypertensive medication classes within 30 days between 01/01/2015 and 06/30/2021, 2 office BP measures recorded 1-90 days apart, ≥1 claim with ICD-9/10-CM diagnosis codes for CKD 3/4, and ≥1 year of continuous enrollment. Baseline BP was defined as uncontrolled (≥130/80 mm Hg) or controlled (<130/80 mm Hg) BP. Outcomes included risk of major adverse cardiovascular events plus (MACE+; stroke, myocardial infarction, heart failure hospitalization), end-stage renal disease (ESRD), healthcare resource utilization events, and costs during follow-up. RESULTS: Of 3,966 patients with stage 3-4 CKD using ≥3 antihypertensive medications, 2,479 had uncontrolled BP and 1,487 had controlled BP. After adjusting for baseline differences, patients with uncontrolled vs. controlled BP had a higher risk of MACE+ (HR [95% CI]: 1.18 [1.03-1.36]), ESRD (1.85 [1.44-2.39]), inpatient hospitalization (rate ratio [95% CI]: 1.35 [1.28-1.43]), and outpatient visits (1.12 [1.11-1.12]) and incurred higher total medical and pharmacy costs (mean difference [95% CI]: $10,055 [$6,741-$13,646] per patient per year). CONCLUSIONS: Patients with aTRH and stage 3-4 CKD and uncontrolled BP despite treatment with ≥3 antihypertensive classes had an increased risk of MACE+ and ESRD and incurred greater healthcare resource utilization and medical expenditures compared with patients taking ≥3 antihypertensive classes with controlled BP.

Prediction of cardiovascular and renal risk among patients with apparent treatment-resistant hypertension in the United States using machine learning methods.

Apparent treatment-resistant hypertension (aTRH), defined as blood pressure (BP) that remains uncontrolled despite unconfirmed concurrent treatment with three antihypertensives, is associated with an increased risk of developing cardiovascular and renal complications compared with controlled hypertension. We aimed to identify the characteristics of aTRH patients with an elevated risk of major adverse cardiovascular events plus (MACE+; defined as stroke, myocardial infarction, or heart failure hospitalization) and end stage renal disease (ESRD). This retrospective cohort study included aTRH patients (BP ≥140/90 mmHg and taking ≥3 antihypertensives) from the United States-based Optum® de-identified Electronic Health Record dataset and used machine learning models to identify risk factors of MACE+ or ESRD. Patients had claims for ≥3 antihypertensive classes within 30 days between January 1, 2015 and June 30, 2021, and two office BP measures recorded 1-90 days apart within 30 days to 11 months after the index regimen date. Of a total 18 797 070 patients identified with any hypertension, 71 100 patients had aTRH. During the study period (mean 25.5 months), 4944 (7.0%) patients had a MACE+ and 2403 (3.4%) developed ESRD. In total, 22 risk factors were included in the MACE+ model and 16 in the ESRD model, and most were significantly associated with study outcomes. The risk factors with the largest impact on MACE+ risk were congestive heart failure, stages 4 and 5 chronic kidney disease (CKD), age ≥80 years, and living in the Southern region of the United States. The risk factors with the largest impact on ESRD risk, other than pre-existing CKD, were anemia, congestive heart failure, and type 2 diabetes. The overall study cohort had a 5-year predicted MACE+ risk of 13.4%; this risk was increased in those in the top 50% and 25% high-risk groups (21.2% and 29.5%, respectively). The overall study cohort had a predicted 5-year risk of ESRD of 6.8%, which was increased in the top 50% and 25% high-risk groups (10.9% and 17.1%, respectively). We conclude that risk models developed in our study can reliably identify patients with aTRH at risk of MACE+ and ESRD based on information available in electronic health records; such models may be used to identify aTRH patients at high risk of adverse outcomes who may benefit from novel treatment interventions.

Assessment of clinical and economic impact of rivaroxaban plus aspirin vs. aspirin alone as a secondary prophylaxis in patients with chronic and symptomatic peripheral arterial disease in the United States.

AIM: The objective in this study was to assess the clinical and economic implications of the inclusion of rivaroxaban as a secondary prophylaxis in patients with chronic or symptomatic peripheral artery disease (PAD) in the United States (US). METHODS: A cost-consequence model was adapted to evaluate the economic impact of rivaroxaban plus aspirin in a hypothetical 1-million-member health plan. The model inputs were taken from multiple sources: efficacy and safety of rivaroxaban + aspirin vs. aspirin alone were abstracted from COMPASS and VOYAGER randomized clinical trials; the prevalence of chronic and symptomatic PAD and incidence rates of clinical events (major adverse cardiac events [MACE], major adverse limb events [MALE], and major bleeding), were abstracted from the analysis of claims data; healthcare costs of clinical events and wholesale acquisition costs for rivaroxaban were abstracted from the literature and Red Book, respectively (2022 USD). One-way sensitivity analyses and subgroup analyses were also conducted. RESULTS: Over one year, with a 5% uptake of rivaroxaban, the model estimated rivaroxaban + aspirin to reduce 21 MACE/MALE events in the PAD patient population. The reduction in these clinical events offsets the increased risk of major bleeding (16 additional events), demonstrating a positive health benefit of the rivaroxaban addition. These benefits led to a $0.27 incremental cost per member per month (PMPM) to a US plan. The major driver of the incremental cost was the cost of rivaroxaban. In a subgroup of patients with the presence of any high-risk factor (heart failure, diabetes, renal insufficiency, or history of vascular disease affecting two or more vascular beds), the incremental PMPM cost was $0.13. CONCLUSIONS: Rivaroxaban + aspirin was found to provide positive net clinical benefit on the annual number of MACE/MALE avoided, with a modest increase in the PMPM cost.

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.

Association of uncontrolled blood pressure in apparent treatment-resistant hypertension with increased risk of major adverse cardiovascular events plus.

Patients with apparent treatment-resistant hypertension (aTRH) are at increased risk of end-organ damage and cardiovascular events. Little is known about the effects of blood pressure (BP) control in this population. Using a national claims database integrated with electronic medical records, the authors evaluated the relationships between uncontrolled BP (UBP; ≥130/80 mmHg) or controlled BP (CBP; <130/80 mmHg) and risk of major adverse cardiovascular events plus (MACE+; stroke, myocardial infarction, heart failure requiring hospitalization) and end-stage renal disease (ESRD) in adult patients with aTRH (taking ≥3 antihypertensive medication classes concurrently within 30 days between January 1, 2015 and June 30, 2021). MACE+ components were also evaluated separately. Multivariable regression models were used to adjust for baseline differences in demographic and clinical characteristics, and sensitivity analyses using CBP <140/90 mmHg were conducted. Patients with UBP (n = 22 333) were younger and had fewer comorbidities at baseline than those with CBP (n = 11 427). In the primary analysis, which adjusted for these baseline differences, UBP versus CBP patients were at an 8% increased risk of MACE+ (driven by a 31% increased risk of stroke) and a 53% increased risk of ESRD after 2.7 years of follow-up. Greater MACE+ (22%) and ESRD (98%) risk increases with UBP versus CBP were seen in the sensitivity analysis. These real-world data showed an association between suboptimal BP control in patients with aTRH and higher incidence of MACE+ and ESRD linked with UBP despite the use of multidrug regimens. Thus, there remains a need for improved aTRH management.

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.

Healthcare Resource Utilization and Costs of Rivaroxaban Versus Warfarin Among Non-valvular Atrial Fibrillation (NVAF) Patients with Diabetes in a US Population.

INTRODUCTION: The healthcare resource utilization (HRU) and costs of oral anticoagulant-naïve patients with non-valvular atrial fibrillation (NVAF) and diabetes initiated on rivaroxaban or warfarin in the United States (US) has not been previously evaluated. METHODS: This retrospective study used data from the Optum's de-identified Clinformatics® Data Mart Database (1 January, 2012 to 30 September, 2021) to evaluate the HRU and costs of adult patients with NVAF and diabetes newly initiated on rivaroxaban or warfarin (on or after January 2013). Inverse probability of treatment weighting (IPTW) was used to adjust for confounding between cohorts. HRU and costs (USD 2021) were assessed per patient-year (PPY) post-treatment initiation. Weighted cohorts were compared using rate ratios (RR) from Poisson regression models, odds ratios (OR) from logistic regression models, and cost differences; 95% confidence intervals (CI) and p values were generated using non-parametric bootstrap procedures. RESULTS: After IPTW, 17,881 and 19,274 patients initiated on rivaroxaban and warfarin were included, respectively (mean age: 73 years; 40% female). During 12 months of follow-up, the rivaroxaban cohort had lower all-cause HRU PPY across all components, including lower rates of inpatient stays (RR: 0.84, 95% CI 0.81, 0.88), outpatient visits (RR: 0.67, 95% CI 0.66, 0.68), and 30 day hospital readmission (OR: 0.75, 95% CI 0.66, 0.83; all p < 0.001) compared to the warfarin cohort. Moreover, rivaroxaban was associated with medical cost savings PPY (mean cost difference: - $9306, 95% CI - $11,769, - $6607), which compensated for higher pharmacy costs relative to warfarin (mean cost difference: $5518, 95% CI $5193, $5839), resulting in significantly lower all-cause total healthcare costs for rivaroxaban versus warfarin (mean cost difference: - $3788, 95% CI - $6258, - $1035; all p < 0.001). CONCLUSION: Among NVAF patients with diabetes in a real-world US setting, rivaroxaban was associated with lower healthcare costs compared to warfarin.

Occurrence of Thromboembolic Events and Mortality Among Hospitalized Coronavirus 2019 Patients: Large Observational Cohort Study of Electronic Health Records.

Background Most symptoms of coronavirus 2019 (COVID-19) are mild; however, some patients experience cardiovascular complications, including thromboembolic events and death. Data are needed to better inform prevention and treatment of these events. This analysis was designed to describe patient characteristics, medication use, thromboembolic events, and all-cause mortality in hospitalized COVID-19 patients in the United States. Methods This retrospective, observational cohort study identified adults hospitalized with COVID-19 (January 21, 2020-January 07, 2021) in the deidentified Optum COVID-19 Electronic Health Records dataset. Thromboembolic events and all-cause mortality were collected at any time during the variable follow-up period (up to 50 weeks). Results Of 181,995 COVID-19 patients who met eligibility criteria, 40,524 (22.3%) were hospitalized with COVID-19. Hospitalized patients had a mean age of 63 years and a Quan-Charlson comorbidity index of 1.3. Anticoagulants were used in 89.2% of patients during hospitalization and in 18.7% of postdischarge patients. Of hospitalized patients, 17.6% had a thromboembolic event during the entire follow-up period (mean time to the first event of 15 days), of whom 13.4% had an event during hospitalization; of discharged patients, 4.3% had a thromboembolic event (mean time from discharge to event of 43 days). Death during the follow-up period was reported in 15.0% of patients. Conclusions In this large, observational cohort study, patients hospitalized with COVID-19 had high rates of thromboembolic events during hospitalization and in the postdischarge period; mortality was also high in this population. Anticoagulant use was common during hospitalization. These findings support further studies to optimize in-hospital and extended prophylaxis for hospitalized COVID-19 patients.

Real-World Analysis of Thromboembolic Events and Mortality of COVID-19 Outpatients in the United States.

Limited data are available on thromboembolic events (TEEs) and mortality in outpatients with coronavirus disease 2019 (COVID-19). This retrospective, observational cohort study identified non-hospitalized COVID-19 outpatients (01/21/2020-01/07/2021) using de-identified Optum® COVID-19 Electronic Health Records data. Patient characteristics, occurrence of TEEs, all-cause mortality, and anticoagulant or thrombolytic medication use were evaluated. Of 1,246,067 patients with COVID-19 diagnosis, 141 471 met entry criteria. Mean (standard deviation [SD]) age was 46.1 (17.2) years, 56.8% were female, 72.9% Caucasian, 11.2% African American, and 11.1% Hispanic. Comorbidity burden was low (mean [SD] Quan-Charlson comorbidity index score of 0.43 [1.10]); however, of those with body mass index data, half were obese. During the follow-up period, a TEE occurred in 1.4%, with the proportion of patients with ischemic stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism being similar (approximately 0.4% each). All-cause mortality was 0.7%. Medications included corticosteroids (13.7%), anticoagulants (4.9%), and antiplatelets (2.9%). Overall, in this large cohort analysis, certain demographic and clinical characteristics of patients who experienced TEEs were identified and may help guide management decisions and future clinical trials for COVID-19 outpatients.

Risk factors for recurrent venous thromboembolism: a real-world analysis.

This study was conducted in patients treated for initial venous thromboembolism (VTE) for approximately 6 months to enhance understanding of the risk factors to inform clinical decision-making about long-term anticoagulation therapy. This retrospective cohort study was conducted using a large administrative claims database in the United States. A Cox proportional hazards model was used to examine demographic and clinical characteristics associated with recurrent VTE. A total of 13 831 patients had an index VTE event, and recurrent VTE occurred in 844 (6.1%) of these patients over a median follow-up of 22.8 months. Baseline comorbidities of arrhythmia, congestive heart failure, and chronic kidney disease were significantly associated with recurrent VTE. During the period of anticoagulation treatment after the index VTE, use of antidepressants was associated with an increased risk of recurrent VTE, whereas use of antibiotics and major surgery were associated with a decreased risk. In the 6 months prior to index VTE, anti-inflammatory agents and major surgery were associated with a decreased risk of recurrent VTE. The type of index VTE was also significantly associated with recurrent VTE, with an increased risk observed in patients with pulmonary embolism (PE) alone or PE with deep vein thrombosis (DVT) versus DVT alone. This real-world analysis identified baseline comorbidities, medications, and index VTE type to be factors predictive of recurrent VTE among patients treated for index VTE for approximately 6 months. Consideration of these factors may assist in the identification of patients who may benefit from extended anticoagulant therapy.

Improved Prediction of Body Mass Index in Real-World Administrative Healthcare Claims Databases.

INTRODUCTION: To continue closing the gap between the predictive modeling and its real-world application, we report a new data-to-prediction pipeline that advanced the state-of-the-art predictive performance of body mass index (BMI) classifications by integrating siloed claims databases via a common data model. METHODS: This study adapted the ensemble-based methodology of the baseline prediction model and focused on removing the silos in the claims databases. We applied the Super Learner machine learning algorithm (SLA) to learn a combined dataset consisting of 50% data from the Optum Date of Death database and 50% data from the IBM MarketScan Commercial Claims and Encounters (CCAE), and omitted the commonly used one-hot-encoding step and used multi-categorical variables directly in the feature engineering process. These developments were then optimized via a standard cross-validation scheme and the performance was evaluated on a holdout test set. RESULTS: Sociodemographic and clinical characteristics were used with (denoted as SLA1) and without (denoted as SLA2) baseline BMI values to predict BMI classifications (≥ 30, ≥ 35, and ≥ 40 kg/m2). Although the newly implemented SLA1 performed similarly to the previous model, with the area under the receiver operating characteristic curve (ROC AUC) being approximately 88% for all BMI classifications, specificity ranging from 90% to 96%, and accuracy ranging from 88% to 93%. The new SLA2 achieved consistently better performance on all metrics across all BMI classes. In particular, the new SLA2 achieved 77-79% in ROC AUC, increasing from the previously reported level (73%). Its specificity improved to the range of 76-90% from 71-86%. Its accuracy improved to the range of 77-86% from 73-80%. Its recall (i.e., sensitivity) improved to the range of 64-78% from 60-76%. CONCLUSIONS: This study demonstrates dramatic improvements in the prediction of BMI across classifications using integrated databases in a common data model for the generation of real-world evidence.

Effectiveness, safety, and healthcare costs associated with rivaroxaban versus warfarin among venous thromboembolism patients with obesity: a real-world study in the United States.

Prior observational studies suggest rivaroxaban is safe and effective among patients with morbid obesity who suffered a venous thromboembolism (VTE) event, but existing data are more limited in the broader population of VTE patients with obesity. This study assessed VTE recurrence, major bleeding, healthcare resource utilization, and healthcare costs among VTE patients with obesity who received rivaroxaban versus warfarin. VTE patients with obesity who initiated rivaroxaban or warfarin after a first VTE (index date) were identified from the IQVIA PharMetrics® Plus database (01/02/2011-09/30/2019). The follow-up period spanned from the index date until health plan disenrollment, end of data availability, cancer diagnosis/treatment, end of the 12 month post-index period, or (for the analysis of major bleeding) anticoagulant discontinuation or switch. Patient characteristics were balanced using inverse probability of treatment weighting. The weighted rivaroxaban (N = 8666) and warfarin cohorts (N = 5946) were well balanced (mean age = 51 years, females = 52%). Over a 9.6 months mean observation period, rivaroxaban users had a significantly lower risk of VTE recurrence [7.0% vs. 8.2%, HR(95% CI) = 0.85(0.75;0.97)] and a similar risk of major bleeding [4.1% vs. 3.6%, HR(95% CI) = 1.11(0.89;1.37)] relative to warfarin users at 12 months. Relative to warfarin users, rivaroxaban users had significantly fewer all-cause outpatient visits [RR(95% CI) = 0.71(0.70;0.74)]. The higher pharmacy costs incurred by rivaroxaban recipients (cost difference = $1252) were offset by lower medical costs (cost difference = - $2515, all p < 0.05) compared with warfarin recipients. Our findings suggest that rivaroxaban is safe and effective versus warfarin, and associated with lower medical costs among VTE patients with obesity.

Effectiveness and Safety of Rivaroxaban versus Warfarin Among Nonvalvular Atrial Fibrillation Patients with Obesity and Polypharmacy.

BACKGROUND: Current evidence suggests that rivaroxaban may be well tolerated and effective in patients with nonvalvular atrial fibrillation (NVAF) and obesity; however, there is limited evidence on the impact of polypharmacy in this population. This study evaluated real-world clinical outcomes with rivaroxaban versus warfarin in patients with NVAF and obesity according to the number of concurrent medications. METHODS: This retrospective cohort study identified patients with one or more pharmacy claim for rivaroxaban or warfarin from two large claims databases. Patients were required to have an atrial fibrillation diagnosis, body mass index ≥ 30 kg/m2 and the presence of polypharmacy (1-4, 5-9, or ≥ 10 concurrent medications). Outcomes of stroke, systemic embolism, and major bleeding were compared between the rivaroxaban and warfarin cohorts after propensity score matching (PSM). RESULTS: A total of 95,875 patients were identified with one or more claim for either rivaroxaban or warfarin. After PSM, patient characteristics were balanced between cohorts (n = 21,547 in each cohort). The overall composite risk of stroke and systemic embolism was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70-0.84; p < 0.001). The risks of ischemic stroke, hemorrhagic stroke, and systemic embolism separately were also significantly reduced with rivaroxaban. Major bleeding risk was similar between cohorts (HR 0.93, 95% CI 0.81-1.06; p = 0.2842), and results were consistent across the three polypharmacy groups. CONCLUSIONS: In this real-world study of NVAF patients with obesity, rivaroxaban was associated with lower risks of stroke and systemic embolism and similar risk of major bleeding versus warfarin across polypharmacy categories.

Adherence and persistence to rivaroxaban in non-valvular atrial fibrillation patients receiving 30- or 90-day supply prescription fills.

BACKGROUND: It is unclear whether 90-day supply fills with rivaroxaban result in better adherence and persistence compared to 30-day supply fills. We assessed patients' adherence and persistence to rivaroxaban at 12- and 24-months in nonvalvular atrial fibrillation (NVAF) patients whose rivaroxaban prescriptions were filled every 30- vs. 90-days. METHODS: Using the IBM MarketScan Commercial and Medicare Supplemental data sets, we identified adult NVAF patients with ≥12-months of continuous insurance coverage who filled a prescription in May 2018 and their immediate subsequent prescription for rivaroxaban for the same days' supply. We propensity score-matched 30- and 90-day rivaroxaban interval fill patients and compared the percentage with a proportion of days covered (PDC) ≥80%, mean PDC, and percentage persistent to rivaroxaban therapy over 12- and 24-months of follow-up. RESULTS: Following propensity score matching, 2237 patients were included in the rivaroxaban 30- and 90-day supply fill cohorts. The proportion of patients with a PDC ≥80% was greater in the 90-day vs. 30-day cohort at both 12-months (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.54-1.97) and 24-months (OR = 1.78, 95%CI = 1.58-2.00), as were mean PDC values (absolute difference in mean PDC = 9.4%, 95%CI = 8.2-10.7% at 12-months and 11.2%, 95%CI = 9.5-12.9% higher at 24-months, respectively). Persistence to rivaroxaban was not found to significantly differ between the 30- and 90-day supply cohorts at 12- or 24-months (assuming a 30-day permissible gap); however, greater persistence was observed with 90-day fills at both time points when a 14-day gap was utilized (HR = 1.22, 95%CI = 1.10-1.36 at 12-months and HR = 1.12, 95%CI = 1.02-1.22 at 24-months). CONCLUSIONS: Dispensing 90-day supply fills with rivaroxaban appears to increase the proportion of patients achieving acceptable (PDC ≥80%) adherence as well as mean adherence compared to 30-day supply fills. Ninety-day rivaroxaban fills may also result in improved persistence vs. 30-day fills.

Healthcare Resource Utilization and Costs of Rivaroxaban Versus Warfarin Among Nonvalvular Atrial Fibrillation Patients with Obesity and Diabetes.

INTRODUCTION: Nonvalvular atrial fibrillation (NVAF) is associated with a substantial economic burden, particularly in patients with comorbid conditions. This study compared healthcare resource utilization (HRU) and costs of rivaroxaban and warfarin in patients with NVAF, obesity, and diabetes. METHODS: A de-identified healthcare claims database was used to identify adult patients newly initiating rivaroxaban or warfarin and having at least one medical claim with a diagnosis of AF, obesity determined by validated algorithm, and at least one claim with a diagnosis of diabetes or for antidiabetic medication from December 2011 to March 2020. Propensity score matching was used to balance the treatment cohorts on the basis of demographics and baseline characteristics. All-cause and NVAF-related HRU rates and costs were compared between treatments using rate ratios, and mean cost differences were calculated on a per patient per year (PPPY) basis. RESULTS: A total of 9999 matched pairs of patients with NVAF, obesity, and diabetes were identified in the rivaroxaban and warfarin cohorts. Rate ratios of all-cause HRU were significantly reduced with rivaroxaban versus warfarin in all healthcare settings evaluated, except emergency room visits. The greatest impact was on physician office visits followed by hospital outpatient and inpatient visits. NVAF-related HRU was significantly lower for rivaroxaban versus warfarin in all care settings. Consistent with these findings, the length of hospital stay was significantly reduced by approximately 4 days among all patients for both all-cause and NVAF-related hospitalizations in the rivaroxaban cohort compared with the warfarin cohort. Rivaroxaban was associated with reductions in all-cause total healthcare costs by more than $5000 PPPY and NVAF-related medical costs by approximately $1100 PPPY. CONCLUSION: In comparison with warfarin, rivaroxaban reduced HRU and costs, particularly hospital inpatient and outpatient visits and physician office visits, in patients with NVAF and comorbidities of obesity and diabetes.

People who are overweight or obese are at risk of developing atrial fibrillation (AF) along with other medical conditions, such as diabetes. Standard therapy with oral anticoagulants or blood thinners is recommended to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF (NVAF). In this study, we evaluated healthcare insurance claims for people with NVAF, obesity, and diabetes who started therapy with warfarin or rivaroxaban from 2011 to 2020 to compare the use and cost of healthcare services, such as hospitalizations and doctor visits, using diagnosis and procedure codes. The study included nearly 20,000 patients with similar characteristics. Patients who started treatment with rivaroxaban used fewer healthcare services for any cause and for those related to NVAF than those who started treatment with warfarin. The difference in use of services was largest for hospital outpatient and inpatient visits and doctor office visits; emergency room visits were only different for those related to NVAF. Length of hospital stay was also shorter for patients receiving rivaroxaban versus those receiving warfarin. These differences in healthcare service use translated into lower costs associated with rivaroxaban versus warfarin. The findings of this study suggest that treatment with rivaroxaban reduces the use of healthcare services compared with warfarin. This difference may be related, in part, to the reduced risks of stroke and systemic embolism observed in other real-world studies with rivaroxaban compared to warfarin. In addition, rivaroxaban does not require routine blood testing, which is required with warfarin treatment.

Effectiveness and safety of rivaroxaban versus warfarin among nonvalvular atrial fibrillation patients with obesity and diabetes.

AIMS: To compare clinical outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity and diabetes. METHODS: Patients aged ≥18 years were identified from a healthcare claims database with the following criteria: newly initiating rivaroxaban or warfarin, ≥1 medical claim with a diagnosis of AF, obesity determined by validated machine learning algorithm, and ≥1 claim with a diagnosis of diabetes or for antidiabetic medication. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models. RESULTS: A total of 9999 matched pairs of NVAF patients with obesity and diabetes who initiated treatment with rivaroxaban or warfarin were included. The composite risk of stroke/SE was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (HR 0.82; 95% CI 0.74-0.90). Risks of ischemic and hemorrhagic strokes were also significantly reduced with rivaroxaban versus warfarin, but not SE. Major bleeding risk was similar between treatment cohorts (HR 0.92; 95% CI 0.78-1.09). CONCLUSIONS: In NVAF patients with comorbidities of obesity and diabetes, rivaroxaban was associated with lower risks of stroke/SE and similar risk of major bleeding versus warfarin.

Economic burden of rivaroxaban and warfarin among nonvalvular atrial fibrillation patients with obesity and polypharmacy.

Aim: Evaluate healthcare resource utilization (HRU) and costs associated with rivaroxaban and warfarin among nonvalvular atrial fibrillation (NVAF) patients with obesity and polypharmacy. Materials & methods: IQVIA PharMetrics® Plus (January 2010-September 2019) data were used to identify NVAF patients with obesity (BMI ≥30 kg/m2) and polypharmacy (≥5 medications) initiated on rivaroxaban or warfarin. Weighted rate ratios and cost differences were evaluated post-treatment initiation. Results: Rivaroxaban was associated with significantly lower rates of HRU, including hospitalization (rate ratio [95% CI]: 0.83 [0.77, 0.92]). Medical costs were reduced in rivaroxaban users (difference [95% CI]: -US$6868 [-US$10,628, -US$2954]), resulting in significantly lower total healthcare costs compared with warfarin users (difference [95% CI]: -US$4433 [-US$8136, -US$582]). Conclusion: Rivaroxaban was associated with lower HRU and costs compared with warfarin among NVAF patients with obesity and polypharmacy in commercially insured US patients.

Comparative Effectiveness and Safety of Rivaroxaban and Warfarin Among Nonvalvular Atrial Fibrillation (NVAF) Patients with Obesity and Polypharmacy in the United States (US).

INTRODUCTION: Current evidence indicates that rivaroxaban may be a safe and effective alternative to warfarin among patients with nonvalvular atrial fibrillation (NVAF) and obesity. However, evidence regarding the impact of polypharmacy is limited in this population. The present study evaluated the effectiveness and safety of rivaroxaban versus warfarin among NVAF patients with obesity and polypharmacy in the US. METHODS: De-identified health insurance claims data from the IQVIA PharMetrics® Plus data (01/2010-09/2019) were used to identify NVAF patients with obesity (BMI ≥ 30 kg/m2) and polypharmacy (≥ 5 medications) initiated on rivaroxaban or warfarin. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances between groups. Study outcomes were evaluated up to 36 months post-treatment initiation and included the composite of stroke or systemic embolism (stroke/SE) and major bleeding. Subgroup analyses were conducted stratified by polypharmacy category (5-9 or ≥ 10 medications). Outcomes were assessed using Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: A total of 7000 and 3920 NVAF patients with obesity and polypharmacy were initiated on rivaroxaban and warfarin, respectively. At 36 months of follow-up, rivaroxaban was associated with a 29% lower risk of stroke/SE relative to warfarin (HR 0.71, 95% CI 0.57, 0.90). Major bleeding risk was not significantly different among rivaroxaban- compared to warfarin-treated patients (HR 0.85, 95% CI 0.70, 1.03). Subgroup analyses yielded results that were largely consistent with the overall polypharmacy analysis. CONCLUSIONS: These results suggest that rivaroxaban is an effective and safe treatment option among NVAF patients with obesity and polypharmacy in a commercially-insured US population.

Healthcare resource utilization and costs of rivaroxaban versus warfarin among non-valvular atrial fibrillation (NVAF) patients with obesity in a US population.

AIM: To assess the real-world healthcare resource utilization (HRU) and costs of patients with non-valvular atrial fibrillation (NVAF) and obesity newly initiated on rivaroxaban or warfarin in the US. METHODS: This retrospective study used IQVIA PharMetrics Plus data (01/2010-09/2019) to evaluate patients (≥18 years) with NVAF and obesity (body mass index ≥30 kg/m2) initiated on rivaroxaban or warfarin (on or after 01/2013). Inverse probability of treatment weighting (IPTW) was used to adjust for confounding between cohorts. HRU and costs were assessed post-treatment initiation. Weighted cohorts were compared using Poisson regression models and cost differences, with 95% confidence intervals (CIs) and p values generated using non-parametric bootstrap procedures. RESULTS: After IPTW, 10,555 and 5,080 patients were initiated on rivaroxaban and warfarin, respectively (mean age: 59 years). At 12 months follow-up, the rivaroxaban cohort had lower all-cause HRU, including fewer hospitalizations (rate ratio [RR]: 0.80, 95% CI: 0.74, 0.87), emergency room visits (RR: 0.89, 95% CI: 0.83, 0.97), and outpatient visits (RR: 0.72, 95% CI: 0.69, 0.77; all p < .05). Medical costs were also reduced in the rivaroxaban cohort (mean difference: -$6,759, 95% CI: -$9,814, -$3,311) due to reduced hospitalization costs (mean difference: -$5,967, 95% CI: -$8,721, -$3,327), resulting in lower total all-cause healthcare costs compared to the warfarin cohort (mean difference: -$4,579, 95% CI: -$7,609, -$1,052; all p < .05). The rivaroxaban cohort also had lower NVAF-related HRU and medical costs driven by lower hospitalization at 12 months post-treatment initiation. HRU and cost reductions associated with rivaroxaban persisted up to 36 months of follow-up. LIMITATIONS: Claims data may have contained inaccuracies and obesity was classified based on ICD diagnosis codes given that patient BMI values were not available. CONCLUSIONS: Rivaroxaban was associated with reduced HRU and costs compared to warfarin among NVAF patients with obesity in a real-world US setting.

Real-world effectiveness and safety of rivaroxaban versus warfarin among non-valvular atrial fibrillation patients with obesity in a US population.

OBJECTIVES: Current evidence indicates that the pharmacokinetic profile of rivaroxaban is not significantly impacted by body weight. However, real-world data are needed to better assess the potential clinical benefits and risks associated with rivaroxaban in non-valvular atrial fibrillation (NVAF) patients with obesity. Thus, our objectives were to assess the real-world effectiveness and safety of rivaroxaban versus warfarin among NVAF patients with obesity in the US nationally representative commercially-insured population. METHODS: Health insurance claims data from the IQVIA PharMetrics Plus database (January 2010-September 2019) were used to identify NVAF patients with obesity (based on diagnosis codes) initiated on rivaroxaban or warfarin. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances between groups. Study outcomes of interest were evaluated up to 36 months post-treatment initiation and included the composite of stroke or systemic embolism (stroke/SE) and major bleeding. Outcomes were compared using Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: A total of 10,555 patients were initiated on rivaroxaban and 5080 patients on warfarin. Following IPTW, the risk of stroke/SE was 26% lower among patients prescribed rivaroxaban relative to warfarin (HR: 0.74, 95% CI: 0.60, 0.91, p = .004) at 36 months. Rivaroxaban-initiated patients had a risk of major bleeding similar to that of warfarin-initiated patients (HR: 0.85, 95% CI: 0.71, 1.02, p = .085). CONCLUSIONS: These results suggest that rivaroxaban is an effective and safe treatment option among NVAF patients with obesity in a commercially-insured US population.