Psychometric properties of the Japanese version of the Kansas City Cardiomyopathy Questionnaire in Japanese patients with chronic heart failure.

BACKGROUND: Heart failure is a worldwide health problem that significantly affects patients' physical function and health state. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific patient-reported outcome measure commonly used for the assessment of health states of patients with heart failure. This study aimed to evaluate the psychometric properties of the Japanese version of the KCCQ. METHODS: Using pooled data of 141 Japanese patients with chronic heart failure from three clinical trials, the Japanese version of the KCCQ was evaluated for validity and reliability, with a focus on the clinical summary score (CSS) and its component domains. For construct validity, the associations of baseline KCCQ scores with New York Heart Association (NYHA) class and the EuroQol five-dimension, three-level (EQ-5D-3L) scores at baseline were analyzed. For reliability, internal consistency was assessed using Cronbach's α, and test-retest reliability (reproducibility) was assessed among stable patients. Responsiveness to changes in patients' clinical status was assessed by analyzing score changes between two timepoints among patients whose health states improved. RESULTS: Among 141 patients (mean age, 73.7 ± 10.9 years), 76.6% were NYHA class II at baseline. For CSS and its component domains (physical limitations, symptom frequency, and symptom severity), baseline scores were all significantly lower in patients with a higher NYHA class (p <  0.001 for all, Jonckheere-Terpstra test). The physical limitations domain and CSS showed a moderate correlation (Spearman's ρ = - 0.40 to - 0.54) with three functional status-related EQ-5D dimensions (mobility, self-care, and usual activities). The Cronbach's standardized α was high (> 0.70) for all KCCQ domain/summary scores. In the test-retest analysis among 58 stable patients, all domain/summary scores minimally changed by 0.3-4.2 points with intraclass correlation coefficients of 0.65-0.84, demonstrating moderate to good reproducibility, except for the symptom stability domain. Among 44 patients with improved health states, all domain/summary scores except for the symptom stability and self-efficacy domains substantially improved from baseline with a medium to large effect size of 0.62-0.88. CONCLUSIONS: The Japanese version of the KCCQ was demonstrated to be a valid and reliable tool for the assessment of symptoms and physical function of Japanese patients with chronic heart failure.

Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The VITALITY-HFpEF Randomized Clinical Trial.

Importance: Patients with heart failure and preserved ejection fraction (HFpEF) are at high risk of mortality, hospitalizations, and reduced functional capacity and quality of life. Objective: To assess the efficacy of the oral soluble guanylate cyclase stimulator vericiguat on the physical limitation score (PLS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ). Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled, multicenter trial of 789 patients with chronic HFpEF and left ventricular ejection fraction 45% or higher with New York Heart Association class II-III symptoms, within 6 months of a recent decompensation (HF hospitalization or intravenous diuretics for HF without hospitalization), and with elevated natriuretic peptides, enrolled at 167 sites in 21 countries from June 15, 2018, through March 27, 2019; follow-up was completed on November 4, 2019. Interventions: Patients were randomized to receive vericiguat, up-titrated to 15-mg (n = 264) or 10-mg (n = 263) daily oral dosages, compared with placebo (n = 262) and randomized 1:1:1. Main Outcomes and Measures: The primary outcome was change in the KCCQ PLS (range, 0-100; higher values indicate better functioning) after 24 weeks of treatment. The secondary outcome was 6-minute walking distance from baseline to 24 weeks. Results: Among 789 randomized patients, the mean age was 72.7 (SD, 9.4) years; 385 (49%) were female; mean EF was 56%; and median N-terminal pro-brain natriuretic peptide level was 1403 pg/mL; 761 (96.5%) completed the trial. The baseline and 24-week KCCQ PLS means for the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 60.0 and 68.3, 57.3 and 69.0, and 59.0 and 67.1, respectively, and the least-squares mean changes were 5.5, 6.4, and 6.9, respectively. The least-squares mean difference in scores between the 15-mg/d vericiguat and placebo groups was -1.5 (95% CI, -5.5 to 2.5; P = .47) and between the 10-mg/d vericiguat and placebo groups was -0.5 (95% CI, -4.6 to 3.5; P = .80). The baseline and 24-week 6-minute walking distance mean scores in the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 295.0 m and 311.8m , 292.1 m and 318.3 m, and 295.8 m and 311.4 m, and the least-squares mean changes were 5.0 m, 8.7 m, and 10.5 m, respectively. The least-squares mean difference between the 15-mg/d vericiguat and placebo groups was -5.5 m (95% CI, -19.7 m to 8.8 m; P = .45) and between the 10-mg/d vericiguat and placebo groups was -1.8 m (95% CI, -16.2 m to 12.6 m; P = .81), respectively. The proportions of patients who experienced symptomatic hypotension were 6.4% in the 15-mg/d vericiguat group, 4.2% in the 10-mg/d vericiguat group, and 3.4% in the placebo group; those with syncope were 1.5%, 0.8%, and 0.4%, respectively. Conclusions and Relevance: Among patients with HFpEF and recent decompensation, 24-week treatment with vericiguat at either 15-mg/d or 10-mg/d dosages compared with placebo did not improve the physical limitation score of the KCCQ. Trial Registration: ClinicalTrials.gov Identifier: NCT03547583.

Cost-effectiveness analysis of treatment of venous thromboembolism with rivaroxaban compared with combined low molecular weight heparin/vitamin K antagonist.

BACKGROUND: Venous thromboembolism (VTE) is a burden on healthcare systems. Standard treatment involves parenteral anticoagulation overlapping with a vitamin K antagonist, an approach that is effective but associated with limitations including the need for frequent coagulation monitoring. The direct oral anticoagulant rivaroxaban is similarly effective to standard therapy as a single-drug treatment for VTE and does not require routine coagulation monitoring. The objective of this economic evaluation was to estimate the cost-effectiveness of rivaroxaban compared with standard VTE treatment from a UK perspective. METHODS: A Markov model was constructed using data and probabilities derived from the EINSTEIN DVT and EINSTEIN PE studies of rivaroxaban and other published sources. Health outcomes included VTE rates, bleeding events avoided, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: There was greater discounted quality-adjusted life expectancy with rivaroxaban than with standard therapy, irrespective of indication and treatment duration. Rivaroxaban was associated with per-patient cost savings for each treatment duration modelled (3, 6 and 12 months), and these were greatest with shorter durations. Rivaroxaban was found to be dominant (cheaper and more effective) and, therefore, cost-effective, in both patients with deep vein thrombosis and pulmonary embolism in all three treatment duration groups, and was also cost-effective in patients requiring lifelong anticoagulation (ICERs: £8677 per QALY and £7072 per QALY in patients with index deep vein thrombosis and pulmonary embolism, respectively). The cost-effectiveness of rivaroxaban was largely insensitive to variations in one-way sensitivity analysis. Probabilistic sensitivity analysis demonstrated that at a threshold of £20,000 per QALY, rivaroxaban had a consistent probability of being cost-effective, compared with LMWH/VKA treatment, of around 80% regardless of index VTE or duration of anticoagulation therapy (3, 6, 12 months or lifelong). CONCLUSIONS: This analysis suggests that rivaroxaban represents a cost-effective choice for acute treatment of deep vein thrombosis and pulmonary embolism and secondary prevention of VTE in the UK, compared with LMWH/VKA treatment, regardless of the required treatment duration.

Patient Perspectives on the Burden of Heart Failure with Preserved Ejection Fraction in a US Commercially Insured and Medicare Advantage Population: A Survey Study.

Background: Patient-reported health related quality of life (HRQOL) is not routinely assessed in clinical practice. Little is known about health status outcomes reported by patients with heart failure with preserved ejection fraction (HFpEF) in non-clinical trial settings. Purpose: To better understand patient burden of HFpEF in terms of HF-specific functional and symptom status, HRQOL, healthcare resource utilization (HCRU) and costs in a US-based commercial and Medicare Advantage insured population. Patients and methods: We conducted a cross-sectional survey of patients with HFpEF and linked their survey and administrative claims data. Consenting, eligible patients completed a survey that included the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ-23) and the PROMIS Global Health-10 (GH-10) questionnaire, as well as clinical and demographic questions. HF medication use, HCRU and costs during the 12-month baseline period before the survey were determined from claims data. Generalized linear regression was used to assess the associations between baseline characteristics and the KCCQ-23 overall summary score. Results: Of 598 survey respondents with survey and claims data, 54.7% were female with mean age 74.0 years. The KCCQ-23 overall summary and clinical summary scores were 64.8 and 63.0, respectively, and the GH-10 physical and mental health summary scores were 39.9 and 45.5. Factors related to lower KCCQ-23 overall summary scores were HF treatment and symptom changes during the past 4-weeks before the survey, hospital admission during the past year, low household income, high comorbidity index, and morbid obesity (BMI>40). Total all-cause healthcare costs were $38,243 during the year prior to the survey, of which 42% were HF-related. Conclusion: Patient-reported outcome measure scores indicated impairment due to HF symptoms and physical limitations in this real-world sample of patients with HFpEF, highlighting a need to assess patient-reported outcomes as well as the clinical and economic outcomes traditionally assessed by clinicians, health systems and payers.

The Anti-Clot Treatment Scale (ACTS) in clinical trials: cross-cultural validation in venous thromboembolism patients.

BACKGROUND: The Anti-Clot Treatment Scale (ACTS) is a 15-item patient-reported instrument of satisfaction with anticoagulant treatment. It includes a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale. Its role in clinical trials and other settings should be supported by evidence that it is both clinically meaningful and scientifically sound. The aim of the study was to evaluate the measurement performance of the ACTS (Dutch, Italian, French, German and English language versions) in patients with venous thromboembolism based on traditional psychometric methods. METHODS: ACTS Burdens and Benefits scale data from a large clinical trial (EINSTEIN DVT) involving 1336 people with venous thromboembolism were analysed at both the scale and item level. Five key psychometric properties were examined using traditional psychometric methods: acceptability, scaling assumptions, reliability (including internal consistency reliability, test-retest reproducibility); validity (including known groups and discriminant validity); and responsiveness. These methods of examination underpin the US Food and Drug Administration recommendations for patient-reported outcome instrument evaluation. RESULTS: Overall, the 12-item ACTS Burdens scale and 3-item ACTS Benefits scale met the psychometric criteria evaluated at both item and scale levels, with the exception of some relatively minor issues in the Dutch language version, which were just below reliability criteria (i.e. alpha = 0.72, test-retest intraclass correlation = 0.79). A consistent finding from item-level evaluations of aggregate endorsement frequencies and skewness suggested that response scales may be improved by reducing the number of response options from five to four. CONCLUSIONS: Both the ACTS Burdens and ACTS Benefits scales consistently satisfied traditional reliability and validity criteria across multiple language datasets, supporting it as a clinically useful patient-reported instrument of satisfaction with anticoagulant treatment in clinical trials. TRIAL REGISTRATION NUMBER: NCT00440193.

Defining changes in physical limitation from the patient perspective: insights from the VITALITY-HFpEF randomized trial.

AIMS: Clinically important thresholds in patient-reported outcomes measures like the Kansas City Cardiomyopathy Questionnaire (KCCQ) have not been defined for patients with heart failure and preserved ejection fraction (HFpEF). The aim of this study was to estimate meaningful thresholds for improvement or worsening in the KCCQ physical limitation score (PLS) in patients with HFpEF. METHODS AND RESULTS: In this pre-specified analysis from VITALITY-HFpEF, anchor- and distribution-based approaches were used to estimate thresholds for improvement or worsening in the KCCQ-PLS using Patient Global Impression of Change (PGIC) as an anchor. The KCCQ-PLS contains six elements, with each increment in response resulting in a change of 4.17 points when converted to a 0-100 scale. The mean change in KCCQ-PLS from baseline to week 12 was calculated for each PGIC group to estimate a meaningful within-patient change. Of 789 patients enrolled, 698 had complete KCCQ-PLS and PGIC data at week 12. The mean (± standard deviation) changes in KCCQ-PLS corresponding to PGIC changes of 'a little better', 'better', and 'much better' were 5.7 ± 18.6, 11.6 ± 19.3, and 18.4 ± 25.3 points, respectively. The scores of patients who responded 'a little better' (n = 177) overlapped substantially with those who reported 'no change' (n = 193; mean change 2.8 ± 18.9). The mean change in KCCQ-PLS for patients responding 'a little worse' (n = 32) was -2.6 ± 18.0 points. The threshold for meaningful within-patient change in KCCQ-PLS based on distribution-based analyses was 12.3 points. Using area under the curve (AUC) analyses of KCCQ-PLS, the sensitivity and specificity of a 4.17-point change were 0.61 and 0.57, for an 8.33-point change they were 0.49 and 0.64, and for a 12.5-point change they were 0.44 and 0.72 for being at least a little better on the PGIC (AUC = 0.54). CONCLUSION: In the VITALITY-HFpEF trial, a change in KCCQ-PLS of ≥8.33 points (corresponding to an improvement in ≥2 response categories of KCCQ-PLS) may represent the minimal clinically important difference for improvement and a change of ≤ -4.17 points (corresponding to a worsening in ≥1 response category of KCCQ-PLS) may suggest deterioration in patients with HFpEF.

Real-Life Multimarker Monitoring in Patients with Heart Failure: Continuous Remote Monitoring of Mobility and Patient-Reported Outcomes as Digital End Points in Future Heart-Failure Trials.

AIMS: Heart failure (HF) affects approximately 26 million people worldwide. With an aging global population, innovative approaches to HF evaluation and management are needed to cope with the worsening HF epidemic. The aim of the Real-Life Multimarker Monitoring in Patients with Heart Failure (REALIsM-HF) study (NCT03507439) is to evaluate a composite instrument comprising remote, real-time, activity-monitoring devices combined with daily electronic patient-reported outcome (ePRO) items in patients who have been hospitalized for HF and are undergoing standard HF assessment (e.g., 6-min walking distance [6MWD], blood biomarkers, Kansas City Cardiomyopathy Questionnaire [KCCQ], and echocardiography). METHODS: REALIsM-HF is an ongoing, 12-week, observational study enrolling 80-100 patients aged ≥45 years with HF with preserved ejection fraction (HFpEF; EF ≥45%) or reduced EF (HFrEF; EF ≤35%). Statistical analyses will include examining the association between data from wearables (the AVIVO© mobile patient management patch or VitalPatch© biosensor, and the DynaPort MoveMonitor©), daily ePROs, and conventional HF metrics (e.g., serum/plasma biomarkers, 6MWD, KCCQ, and echocardiographic parameters). The feasibility of and patient compliance with at-home devices will be documented, and the data captured for the purpose of establishing reference values in patients with HFpEF or HFrEF will be summarized. CONCLUSIONS: The REALIsM-HF study is to evaluate the longitudinal daily activity profiles of patients with HF and correlate these with changes in serum/plasma biomarker profiles, symptoms, quality of life, and cardiac function and morphology to inform the use of wearable activity monitors for developing novel therapies and managing patients.

Comparing the EQ-5D-5L utility index based on value sets of different countries: impact on the interpretation of clinical study results.

OBJECTIVE: To compare the country-specific value sets of the EQ-5D-5L utility index and to evaluate the impact on the interpretation of clinical study results. Six country value sets from Canada, England, Japan, Korea, Netherlands and Uruguay were obtained from literature. In addition, ten crosswalk value sets were downloaded from the EuroQol.org website. RESULTS: For each of the 3125 possible health states the difference between the country with the highest index and the country with the lowest index was calculated. The median difference was 0.417 across the health states. When analyzing multinational clinical studies, country-specific value sets should be used to evaluate treatment effects. Additional country-specific analyses are needed.

Rationale and Design of the VITALITY-HFpEF Trial.

Background The VITALITY-HFpEF trial (Evaluate the Efficacy and Safety of the Oral sGC Stimulator Vericiguat to Improve Physical Functioning in Daily Living Activities of Patients With Heart Failure and Preserved Ejection Fraction) is designed to determine the efficacy and safety of a novel oral soluble guanylate cyclase stimulator, vericiguat, on quality of life and exercise tolerance in heart failure patients with preserved ejection fraction (HFpEF). Impaired physical functioning reduces the quality of life in patients with HFpEF. The primary goal of HF treatment along with improving survival is to improve function, reduce symptoms, and maximize quality of life. Abnormal cyclic guanosine monophosphate signaling may contribute to physical limitations in patients with HFpEF via central and peripheral mechanisms. Exploratory post hoc analyses from a prior trial showed that vericiguat can improve patient-relevant domains of the Kansas City Cardiomyopathy Questionnaire, especially the physical limitation score. Methods and Results VITALITY-HFpEF is a placebo-controlled, double-blind, multi-center, phase IIb trial of ≈735 patients, ≥45 years with HFpEF and ejection fraction ≥45% who will be randomized 1:1:1 to placebo, 10 mg, or 15 mg vericiguat. The primary end point is change in Kansas City Cardiomyopathy Questionnaire physical limitation score from baseline to week 24 and change in 6-minute walk test from baseline to week 24 is the secondary end point. Conclusions VITALITY-HFpEF is the first trial designed to assess the efficacy of vericiguat in patients with HFpEF using the Kansas City Cardiomyopathy Questionnaire physical limitation score as a novel primary end point. This study will also extend the prior dosing experience with vericiguat in HF by studying the safety and efficacy of a 15 mg dose. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT03547583.

Epidemiology of first and recurrent venous thromboembolism in patients with active cancer. A population-based cohort study.

Population studies on the incidence of venous thromboembolism (VTE) in patients with active cancer are limited. An observational cohort study was undertaken to estimate the incidence of first and recurrent VTE. The source population consisted of all patients in the UK Clinical Practice Research Datalink, with additional information on hospitalisation and cause of death, between 2001 and 2011. A cancer-related clinical diagnosis or therapy within the 90 days before or after a VTE constituted an active-cancer-associated VTE. Incidence rates of first VTE among patients with active cancer and incidence rates of recurrent VTE during the 10-year observational period after a first VTE event were estimated. Incidence rates of all-cause mortality and age- and gender-specific mortality were also calculated. There were 6,592 active-cancer-associated VTEs with a total of 112,738 cancer-associated person-years of observation. The incidence rate of first VTE in patients with active cancer was 5.8 (95 % confidence interval 5.7-6.0) per 100 person-years. A first VTE recurrence was observed in 591 patients. The overall incidence rate for recurrence was 9.6 (95 % confidence interval 8.8-10.4) per 100 person-years, with a peak at 22.1 in the first six months. Recurrence rates were similar after initial pulmonary embolism and after initial deep-vein thrombosis. The mortality risk after VTE was considerable, with 64.5 % mortality after one year and 88.1 % after 10 years. VTE in patients with active cancer is common and associated with high recurrence and mortality rates. Efforts are needed to prevent VTE and reduce recurrence, especially in the first year after VTE diagnosis.

Patient-reported outcomes in the SOluble guanylate Cyclase stimulatoR in heArT failurE patientS with PRESERVED ejection fraction (SOCRATES-PRESERVED) study.

AIMS: Exploratory assessment of the potential benefits of the novel soluble guanylate cyclase stimulator vericiguat on health status in patients with heart failure (HF) with preserved ejection fraction. METHODS AND RESULTS: The SOCRATES-PRESERVED trial randomized patients with chronic HF and ejection fraction ≥ 45% within 4 weeks of decompensation to 12 weeks of treatment with titrated doses of vericiguat (1.25, 2.5, 5, and 10 mg once daily) or placebo. Health status was assessed with the disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ) and the generic health-related quality of life measure EQ-5D. In total, 477 patients were randomized 12.9 ± 9.0 days after hospitalization or if requiring outpatient treatment with intravenous diuretics for HF. Baseline KCCQ clinical summary score (CSS), a combination of symptom and physical function domains, was 52.3 ± 20.4 in the 10 mg arm and 54.1 ± 23.0 in placebo, and EQ-5D US index score was 0.74 ± 0.2 and 0.73 ± 0.2, respectively. A larger proportion of patients treated with vericiguat in the 10 mg arm, compared with placebo, achieved clinically meaningful improvements in KCCQ-CSS (82.0% vs. 59.0%, number needed to treat = 4.35, P = 0.0052). Important domains of the KCCQ as well as EQ-5D scores demonstrated a dose-dependent relationship with vericiguat. In the 10 mg arm, the mean physical limitations domain increased by +17.2 ± 19.1 at 12 weeks, compared with +4.5 ± 21.6 in placebo (P = 0.0009). The EQ-5D US index score increased by +0.064 ± 0.167 in the 10 mg arm, compared with a decrease of -0.009 ± 0.195 in placebo (P = 0.0461). Improvements in KCCQ and EQ-5D scores paralleled physician-assessed NYHA class and clinical congestion. CONCLUSION: Vericiguat, in exploratory hypothesis-generating analyses, was associated with clinically important improvements in patients' health status, as assessed by the KCCQ and EQ-5D. Further studies should be conducted to test the hypothesis that vericiguat improves physical functioning and health-related quality of life in patients with HF with preserved ejection fraction.

Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of pulmonary embolism; results from the EINSTEIN PE trial.

INTRODUCTION: Rivaroxaban is an oral, direct Factor Xa inhibitor, approved for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT) and the secondary prevention of recurrent PE and DVT as a fixed-dose, monotherapy regimen that does not require initial heparinisation, routine coagulation monitoring or dose adjustment. Approval in this indication was supported by results from EINSTEIN PE, a large, randomised, open-label study that compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy in patients with acute symptomatic PE with or without DVT. MATERIALS AND METHODS: Patient-reported treatment satisfaction was evaluated in a predefined subanalysis of EINSTEIN PE to enable monitoring and optimisation of patient-reported outcomes and, therefore, patient compliance. As part of EINSTEIN PE, 2,397 patients in seven countries were asked to complete a validated measure of treatment satisfaction, the Anti-Clot Treatment Scale (ACTS) throughout the duration of treatment (up to 12 months). RESULTS: Patients reported greater satisfaction in the rivaroxaban treatment arm as compared with the enoxaparin/VKA treatment arm. Treatment with rivaroxaban was reported as being significantly less burdensome than enoxaparin/VKA therapy, and the benefits of treatment were significantly greater. CONCLUSION: Rivaroxaban treatment resulted in improved treatment satisfaction compared with enoxaparin/VKA in PE patients, particularly in reducing patient-reported anticoagulation burden.

Length of stay and economic consequences with rivaroxaban vs enoxaparin/vitamin K antagonist in patients with DVT and PE: findings from the North American EINSTEIN clinical trial program.

OBJECTIVE: Venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [(PE]) represents a substantial economic burden to the healthcare system. Using data from the randomized EINSTEIN DVT and PE trials, this North American sub-group analysis investigated the potential of rivaroxaban to reduce the length of initial hospitalization in patients with acute symptomatic DVT or PE. METHODS: A post-hoc analysis of hospitalization and length-of-stay (LOS) data was conducted in the North American sub-set of patients from the randomized, open-label EINSTEIN trial program. Patients received either rivaroxaban (15 mg twice daily for 3 weeks followed by 20 mg once daily; n = 405) or dose-adjusted subcutaneous enoxaparin overlapping with (guideline-recommended 'bridging' therapy) and followed by a vitamin K antagonist (VKA) (international normalized ratio = 2.0-3.0; n = 401). The open-label study design allowed for the comparison of LOS between treatment arms under conditions reflecting normal clinical practice. LOS was evaluated using investigator records of dates of admission and discharge. Analyses were carried out in the intention-to-treat population using parametric tests. Costs were applied to the LOS based on weighted mean cost per day for DVT and PE diagnoses obtained from the Healthcare Cost and Utilization Project dataset. RESULTS: Of 382 patients hospitalized, 321 (84%), had acute symptomatic PE; few DVT patients required hospitalization. Similar rates of VTE patients were hospitalized in the rivaroxaban and enoxaparin/VKA treatment groups, 189/405 (47%) and 193/401 (48%), respectively. In hospitalized VTE patients, rivaroxaban treatment produced a 1.6-day mean reduction in LOS (median = 1 day) compared with enoxaparin/VKA (mean = 4.5 vs 6.1; median = 3 vs 4), translating to total costs that were $3419 lower in rivaroxaban-treated patients. CONCLUSION: In hospitalized North American patients with VTE, treatment with rivaroxaban produced a statistically significant reduction in LOS. When treating DVT and PE patients, clinicians should consider newer anti-coagulants with less complex treatment regimens.

Reduction in the length of stay with rivaroxaban as a single-drug regimen for the treatment of deep vein thrombosis and pulmonary embolism.

OBJECTIVE: The phase III EINSTEIN DVT and EINSTEIN PE trials demonstrated the potential of oral rivaroxaban for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). The length of initial hospitalization in patients presenting with either symptomatic DVT or PE was assessed using hospitalization records from these trials. METHODS: Analyses were carried out in the intention-to-treat population, using non-parametric and parametric statistical methods. RESULTS: Overall, 52% (1781/3434) of EINSTEIN DVT patients and 90% (4328/4821) of EINSTEIN PE patients were admitted to hospital. The proportion of hospitalized patients with a length of stay of five or fewer days receiving rivaroxaban was 54% compared with 31% for enoxaparin/vitamin K antagonist (VKA) in patients with DVT. For patients with PE, the corresponding values were 45% and 33%. Stays of 6-10 days were observed in 29% of rivaroxaban-treated patients compared with 45% of enoxaparin/VKA-treated patients for DVT. For patients with PE, these values were 39% and 46% in the rivaroxaban and enoxaparin/VKA groups, respectively. Overall, length of stay was significantly shorter in the rivaroxaban group, compared with the enoxaparin/VKA group across all analyses performed (p < 0.0001). Across regions, the observed admission rates and length of stay duration varied greatly: Asia had the longest overall hospitalization rates, whereas the lowest rates were reported in North America, Australia and New Zealand. Nevertheless, a consistent trend was observed: length of hospital stay in patients with DVT or PE receiving rivaroxaban was shorter than, or at least similar to, patients receiving enoxaparin/VKA. CONCLUSION: A single-drug regimen with rivaroxaban may reduce the burden on healthcare systems and patients, and provides effective and well tolerated treatment. The studies shared an open-label design that allowed comparison of initial hospitalization, but limitations include the well monitored clinical trial setting in which decisions on admission and discharge could vary from real-world management.

Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of acute symptomatic deep-vein thrombosis.

Rivaroxaban, an oral, direct factor Xa inhibitor, has been approved for the treatment of deep-vein thrombosis (DVT) and pulmonary embolism (PE) and the prevention of recurrent DVT and PE as a fixed-dose, single-drug regimen that does not require initial heparinisation, routine coagulation monitoring or dose adjustment. This study evaluated patient-reported treatment satisfaction in EINSTEIN DVT--a large, open-label, randomised study that compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy in patients with acute symptomatic DVT without PE. As part of EINSTEIN DVT, a total of 1,472 patients in seven countries were asked to complete a new, validated measure of treatment satisfaction--the Anti-Clot Treatment Scale (ACTS)--at scheduled visits throughout 12 months of treatment. ACTS scores were compared between study groups in the intention-to-treat population. Patients reported greater satisfaction in the rivaroxaban group compared with the enoxaparin/VKA group, with higher mean ACTS scores across visits. Mean ACTS Burdens scores were 55.2 vs 52.6 (p<0.0001) in favour of rivaroxaban, equivalent to a moderate effect size of 0.42. The treatment effect was consistent over time, with the mean score difference ranging from 2.18 (month 2) to 3.18 (month 12). Overall mean ACTS Benefits scores were 11.7 vs 11.5 in favour of rivaroxaban (p=0.006). This was associated with a small overall effect size of 0.12. The improvement in ACTS Benefits for rivaroxaban became apparent at month 2 and subsequent visits. Rivaroxaban results in improved treatment satisfaction compared with enoxaparin/VKA among patients with DVT, particularly in reducing patient-reported anticoagulation burden.