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.

Effectiveness and safety of rivaroxaban compared with low-molecular-weight heparin in cancer-associated thromboembolism.

Guidelines provide differing recommendations regarding direct-acting oral anticoagulants vs low-molecular-weight heparin (LMWH) for treatment of cancer-associated thrombosis (CAT). This study was undertaken to evaluate the effectiveness and safety of rivaroxaban vs LMWH for treatment of CAT. Using US Surveillance, Epidemiology and End Results-Medicare-linked data from 2013 through 2016, we evaluated adults with active breast, lung, ovarian, or pancreatic cancer, who were admitted to the hospital or treated in the emergency department for CAT and were prescribed rivaroxaban or LMWH for outpatient anticoagulation. Patients with luminal gastrointestinal or genitourinary cancers were excluded. Rivaroxaban and LMWH users were 1:1 propensity score matched. Outcomes included the composite of recurrent thrombosis or major bleeding, each outcome separately, and mortality at 6 months, using an intent-to-treat approach. On-treatment analysis after 12 months was also performed. Proportional hazards models for the subdistribution of competing risk were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 529 rivaroxaban- and 529 LMWH-treated patients with CAT. Rivaroxaban was not associated with differences in risk of the composite outcome (HR, 0.71; 95% CI, 0.41-1.22), major bleeding (HR, 1.01; 95% CI, 0.50-2.01), or mortality (HR, 0.87; 95% CI, 0.70-1.07) vs LMWH, but it reduced recurrent thrombosis (HR, 0.37; 95% CI, 0.15-0.95). On-treatment analysis at 12 months showed similar results. Rivaroxaban may be a reasonable alternative to LMWH for patients with CAT without gastrointestinal or genitourinary cancer.

Communication of Medication Nonmedical Switching Policies and Procedures by Insurance Companies: Results of an E-Survey.

PURPOSE: Nonmedical switching is defined as a change in a stable patient's prescribed medication to a clinically distinct, nongeneric alternative for reasons other than lack of clinical response, adverse effects, or poor adherence. Nonmedical switching often results from formulary changes implemented by insurers to lower medication costs. We sought to survey randomly sampled physicians to elicit their opinions regarding insurers' communication about nonmedical switching. METHODS: We performed an online, cross-sectional survey of licensed, practicing physicians who were >2 years but <30 years out of residency and/or fellowship, who practiced in an internal medicine, family medicine, or specialist setting, spent ≥10% of their work time providing direct patient care, and had received at least 1 request for a nonmedical switch for ≥1 patient in the prior 12 months. The survey was fielded from November to December 2018. We report weighted percent responses categorized from 5- or 7-point Likert scale questions. FINDINGS: E-mail invitations were sent to 13,117 randomly sampled physicians, and 1818 opened the e-mail and followed the embedded survey link to participate. Of these, 1010 total physicians (55.5%), 606 primary care and 404 specialists, who treated patients experiencing nonmedical switching in the prior 12 months completed the survey. A few physicians were notified about nonmedical switches by insurers; more frequently physicians learned about them from pharmacies serving their patients. Notification frequently occurred at or after a refill came due. Notification via electronic medical record or insurer letter was less frequent. Few thought that insurers clearly communicated information about alternative medications when a nonmedical switch was required, and most disagreed that insurers provided clear procedures, timelines, and methods to track challenges. Nearly all agreed that insurers should provide supporting documentation or rationale for nonmedical switches and specifics on alternatives. Respondents overwhelmingly agreed that steps to improve communication and physicians' and patients' ability to navigate nonmedical switches or challenge procedures should be implemented. IMPLICATIONS: This survey of primary care and speciality physicians suggests that physicians believe that insurers' current level of communication regarding nonmedical switching is suboptimal. Respondents suggested that insurers did not optimally communicate information about alternative medications when a nonmedical switch was required and did not provide clear procedures, timelines, and methods to track challenges. A preponderance of physicians agreed that steps to improve physician-insurer communication to aid in the navigation of nonmedical switch and to challenge procedures should be implemented. If not addressed, these identified nonmedical switch communication issues may have a negative effect on achieving the quadruple aim of enhancing patient experience, improving population health, reducing costs, and improving the work life of health care practitioners and their staff.

Four-year incidence of major adverse cardiovascular events in patients with atherosclerosis and atrial fibrillation.

BACKGROUND: There is a paucity of contemporary data assessing the implications of atrial fibrillation (AF) on major adverse cardiovascular events (MACE) in patients with or at high-risk for atherosclerotic disease managed in routine practice. HYPOTHESIS: We sought to evaluate the 4-year incidence of MACE in patients with or at risk of atherosclerotic disease in the presence of AF. METHODS: Using US MarketScan data, we identified AF patients ≥45 years old with billing codes indicating established coronary artery disease, cerebrovascular disease, or peripheral artery disease or the presence of ≥3 risk factors for atherosclerotic disease from January 1, 2013 to December 31, 2013 with a minimum of 4-years of available follow-up. We calculated the 4-year incidence of MACE (cardiovascular death or hospitalization with a primary billing code for myocardial infarction or ischemic stroke). Patients were further stratified by CHA2 DS2 -VASc score and oral anticoagulation (OAC) use at baseline. RESULTS: We identified 625,951 patients with 4-years of follow-up, of which 77,752 (12.4%) had comorbid AF. The median (25%, 75% range) CHA2 DS2 -VASc score was 4 (3, 5) and 64% of patients received an OAC at baseline. The incidence of MACE increased as CHA2 DS2 -VASc scores increased (P-interaction<.0001 for all). AF patients receiving an OAC were less likely to experience MACE (8.9% vs 11.6%, P < .0001) including ischemic stroke (5.4% vs 6.7%, P < .0001). CONCLUSION: Comorbid AF carries a substantial risk of MACE in patients with or at risk of atherosclerotic disease. MACE risk increases with higher CHA2 DS2 -VASc scores and is more likely in patients without OAC.

Physicians' perspectives regarding non-medical switching of prescription medications: Results of an internet e-survey.

BACKGROUND: Physicians are in an ideal position to describe the impact of medication non-medical switching (switching commonly due to formulary changes by insurer for reasons unrelated to patient health) on their practice dynamics and patient care. We sought to examine physicians' openness to requests for non-medical switching and their experiences and opinions regarding the impact of non-medical switching on their practice, staff and patients. METHODS: An online survey of randomly-sampled physicians spending ≥10% of time providing patient care and having received ≥1 non-medical switch request during the prior 12-months. The impact of non-medical switching on clinical decision-making process; professional experience with clinical practice, patient-physician relationship, insurance process; and perceived impact on practice, staff and patients were assessed. Weighted percent responses were calculated. RESULTS: We sampled 1,010 physicians (response rate = 55.5%). Many responded being frequently not amenable (26.0%) or had reservations (41.8%) to non-medical switch requests; with >50% indicating patient stability on current therapy and suboptimal alternatives as factors frequently influencing amenability. Physicians agreed non-medical switching can create ethical concerns (clinical judgement, autonomy, ability to treat per guidelines; 74.8%, 82.3%, 53.5%, respectively), while forcing them to take responsibility for insurers' decisions (81.1%) and diverting their clinical time (84.3%). Most indicated non-medical switching increased practice burden (administrative, non-billable interactions, additional staffing, non-office patient contact, calls to/from the pharmacy; 85.0%, 72.5%, 62.2%, 64.2%, 69.5%, respectively). Physicians felt insurer processes discouraged non-medical switch challenges (76.7%) and required inconvenient lengths-of-time (76.1%) speaking to insurer representatives without proper expertise (62.0%). They believed non-medical switching negatively impacted aspects of care (effectiveness, side-effects, medication adherence and abandonment, out-of-pocket costs, medication errors; 46.5%, 53.2%, 50.6%, 49.4%, 59.6%, 54.5%, respectively). CONCLUSIONS: Physicians were frequently not amenable or had reservations regarding non-medical switching. They noted ethical concerns due to non-medical switching. Most felt non-medical switches burdened their practice and negatively impacted care.

Effectiveness, treatment durability, and treatment costs of canagliflozin and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes in the USA.

Introduction: This real-world study compared glycemic effectiveness, treatment durability, and treatment costs with canagliflozin 300 mg versus any dose of glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes mellitus (T2DM) in the USA. Research design and methods: A retrospective cohort study using administrative claims and laboratory data (1 April 2012 to 28 February 2017) from the HealthCore Integrated Research Database were used to assess mean HbA1c at 3-month intervals, achievement of HbA1c thresholds (<7.0%, <8.0%, <9.0%), and treatment durability (ie, adherence, discontinuation, switching, treatment failure (ie, exceeding threshold (7.0%, 8.0%, 9.0%), having a prescription for a new antihyperglycemic agent)) in adults with T2DM who initiated canagliflozin 300 mg or any dose of a GLP-1 receptor agonist. Medication costs were calculated for adherent patients. Results: There were no significant differences in the primary outcome of HbA1c levels at 3-month intervals (≤12 months) in the canagliflozin 300 mg versus any dose GLP-1 receptor agonist cohort. The likelihood of achieving HbA1c<8.0% was not different (p=0.666), the likelihood of achieving HbA1c<7.0% was lower (p=0.016), and the likelihood of achieving HbA1c<9.0% was higher (p=0.020) in the canagliflozin 300 mg versus any dose GLP-1 receptor agonist cohort. The likelihood of treatment failure after reaching any HbA1c target was not different between cohorts. A higher proportion of patients were adherent to treatment (p<0.0001) and a lower proportion discontinued (p<0.0001) or switched medication (p=0.023) in the canagliflozin 300 mg versus any dose GLP-1 receptor agonist cohort. Over 1 year, medication costs were $1421 (p<0.001) lower with canagliflozin 300 mg than any dose of GLP-1 receptor agonists. Conclusions: This real-world, US-based study found that initiation of canagliflozin 300 mg versus any dose of a GLP-1 receptor agonist in patients with T2DM was not associated with significant differences in the primary outcome of HbA1c levels at 3-month intervals for up to 12 months after index, but showed better adherence, less discontinuation, and lower drug acquisition costs compared with initiation of any dose of a GLP-1 receptor agonist.

Cost and inpatient burden of peripheral artery disease: Findings from the National Inpatient Sample.

BACKGROUND AND AIMS: We aimed to examine the prevalence, demographics, clinical outcomes and economic burden of hospitalizations for patients with PAD. METHODS: Using the National Inpatient Sample, we retrospectively evaluated patients hospitalized with PAD in 2014. Hospitalizations in patients with PAD were identified by the presence of an International Classification of Diseases-9th Revision (ICD-9) diagnosis code of 440.20-440.24. We calculated hospitalization rates/100,000 patients, the proportion of hospitalizations with a major adverse limb event (MALE), as well as minor amputation, mortality, median (interquartile range) length-of-stay (LOS) and treatment costs (in 2017 US$). A separate analysis of hospitalizations of patients with clinical limb ischemia defined as Fontaine class III or IV PAD (440.22, resting pain; 440.23-440.24, ulcers or gangrene) was also performed. RESULTS: We identified 286,160 hospitalizations for patients with PAD. The rate of hospitalizations for PAD was 89.5/100,000, with 137,050 (or 45%) of these having Fontaine class III-IV disease. The proportion of hospitalizations resulting in MALE, major or minor lower extremity amputation or in-hospital death was 45.8%, 8.9%, 8.2% and 3.1%, respectively. Median hospital LOS was 5 (3, 9) days and costs were $15,755 ($8972, $27,800), resulting in an annual cost burden for hospitalization of patients with PAD of ∼$6.31 billion. In hospitalizations of Fontaine class III-IV PAD, MALE, major and minor amputation and death occurred in 60.9%, 16.8%, 15.8% and 3.3% of cases, respectively. Median LOS and costs were 7 (4, 11) days and $18,984 ($10,913, $31,816). CONCLUSIONS: Hospitalizations of patients with PAD represent a substantial medical and financial burden for patients and the US healthcare system.

Healthcare costs of stroke and major bleeding in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants.

Objective: To assess long-term healthcare costs related to ischemic stroke and systemic embolism (stroke/SE) and major bleeding (MB) events in patients with non-valvular atrial fibrillation (NVAF) treated with non-vitamin K antagonist oral anticoagulants (NOACs). Materials and methods: Optum's Clinformatics Data Mart database from 1/2009-12/2016 was analyzed. Adult patients with ≥1 stroke/SE hospitalization (index date) were matched 1:1 to patients without stroke/SE (random index date), based on propensity scores. Patients with an MB event were matched to patients without MB. All patients had an NOAC dispensing overlapping index date, ≥12 months of eligibility pre-index date, and ≥1 NVAF diagnosis. The observation period spanned from the index date until the earliest date of death, switch to warfarin, end of insurance coverage, or end of data availability. Mean costs were evaluated: (1) per-patient-per-year (PPPY) and (2) at 1, 2, 3, and 4 years using Lin's method. Results: The cost differences were, respectively, $48,807 and $28,298 PPPY for NOAC users with stroke/SE (n = 1,340) and those with MB (n = 3,774) events compared to controls. Cost differences of patients with vs without stroke/SE were $49,876, $51,627, $57,822, and $60,691 at 1, 2, 3, and 4 years post-index, respectively (p < 0.001). These cost differences were $31,292, $35,658, $44,069, and $47,022 for patients with vs without MB after 1, 2, 3, and 4 years post-index, respectively (p < 0.001). Limitations: Limitations include unobserved confounders, coding and/or billing inaccuracies, limited sample sizes over longer follow-up, and the under-reporting of mortality for deaths occurring after 2011. Conclusions: The incremental healthcare costs incurred by patients with vs without stroke/SE was nearly twice as high as those of patients with vs without MB. Moreover, each additional year up to 4 years after the first event was associated with an incremental cost for patients with a stroke/SE or MB event compared to those without an event.

The value of sPESI for risk stratification in patients with pulmonary embolism.

INTRODUCTION: Various risk stratification methods exist for patients with pulmonary embolism (PE). We used the simplified Pulmonary Embolism Severity Index (sPESI) as a risk-stratification method to understand the Veterans Health Administration (VHA) PE population. MATERIALS AND METHODS: Adult patients with ≥ 1 inpatient PE diagnosis (index date = discharge date) from October 2011-June 2015 as well as continuous enrollment for ≥ 12 months pre- and 3 months post-index date were included. We defined a sPESI score of 0 as low-risk (LRPE) and all others as high-risk (HRPE). Hospital-acquired complications (HACs) during the index hospitalization, 90-day follow-up PE-related outcomes, and health care utilization and costs were compared between HRPE and LRPE patients. RESULTS: Of 6746 PE patients, 95.4% were men, 67.7% were white, and 22.0% were African American; LRPE occurred in 28.4% and HRPE in 71.6%. Relative to HRPE patients, LRPE patients had lower Charlson Comorbidity Index scores (1.0 vs. 3.4, p < 0.0001) and other baseline comorbidities, fewer HACs (11.4% vs. 20.0%, p < 0.0001), less bacterial pneumonia (10.6% vs. 22.3%, p < 0.0001), and shorter average inpatient lengths of stay (8.8 vs. 11.2 days, p < 0.0001) during the index hospitalization. During follow-up, LRPE patients had fewer PE-related outcomes of recurrent venous thromboembolism (4.4% vs. 6.0%, p = 0.0077), major bleeding (1.2% vs. 1.9%, p = 0.0382), and death (3.7% vs. 16.2%, p < 0.0001). LRPE patients had fewer inpatient but higher outpatient visits per patient, and lower total health care costs ($12,021 vs. $16,911, p < 0.0001) than HRPE patients. CONCLUSIONS: Using the sPESI score identifies a PE cohort with a lower clinical and economic burden.

Influence of Polypharmacy on the Effectiveness and Safety of Rivaroxaban Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation.

STUDY OBJECTIVE: Patients with nonvalvular atrial fibrillation (NVAF) often have multiple comorbidities requiring concomitant medications in addition to their oral anticoagulant (OAC). The objective of this study was to evaluate the impact of polypharmacy on the effectiveness and safety of rivaroxaban versus warfarin in patients with NVAF managed in routine clinical practice. DESIGN: Retrospective claims analysis. DATA SOURCE: United States Truven MarketScan database (November 2012-March 2017). PATIENTS: Adults who were OAC naïve during the 12 months before the day of the first qualifying rivaroxaban or warfarin dispensing (index date); had at least two International Classification of Diseases, Ninth or Tenth Revision diagnosis codes for atrial fibrillation without codes suggesting valvular heart disease; had at least 12 months of continuous insurance coverage prior to the qualifying OAC dispensing; and were experiencing polypharmacy (concomitant prescription claims for five or more unique chronic medication claims) were included. Patients who had concomitant prescription claims for ≥ 10 unique chronic medication claims constituted the substantial polypharmacy cohort used in the secondary analysis. Patients receiving rivaroxaban were propensity-score matched in a 1:1 ratio to patients receiving warfarin (13,981 patients in each polypharmacy OAC group, and 1765 patients in each substantial polypharmacy OAC group). MEASUREMENTS AND MAIN RESULTS: Patients were followed until occurrence of an event (stroke or systemic embolism [SSE] combined [primary effectiveness outcome] or major bleeding [primary safety outcome]), OAC discontinuation or switch (30-day permissible gap), insurance disenrollment, or end of follow-up period. Rates of SSE, ischemic stroke, and major bleeding were compared by using Cox regression, reported as hazard ratios (HRs) and 95% confidence intervals (CIs). In patients with NVAF taking five or more chronic medications, rivaroxaban was associated with a 34% (95% CI 12-50) and 40% (95% CI 16-57) hazard reduction of SSE and ischemic stroke, respectively. Occurrence of major bleeding was similar between OAC cohorts (HR 1.08, 95% CI 0.92-1.28). A secondary analysis in patients with NVAF with substantial polypharmacy (taking ≥ 10 chronic medications) was also performed. Similar trends in SSE (HR 0.44), ischemic stroke alone (HR 0.62), and major bleeding (HR 1.07) were observed in patients with NVAF who had substantial polypharmacy, although 95% CIs crossed 1.0 for each outcome in this smaller study cohort. CONCLUSION: This real-world study suggests that in the setting of polypharmacy and NVAF, rivaroxaban is an effective and safe alternative to warfarin.

Clinical and Economic Outcomes in Low-risk Pulmonary Embolism Patients Treated with Rivaroxaban versus Standard of Care.

BACKGROUND: Rivaroxaban, a fixed-dose oral direct factor Xa inhibitor, does not require continuous monitoring and thus reduces the hospital stay and economic burden in low-risk pulmonary embolism (LRPE) patients. Study Question: What is the effectiveness of rivaroxaban versus the standard of care (SOC; low-molecular-weight heparin, unfractionated heparin, warfarin) among LRPE patients in the Veterans Health Administration? STUDY DESIGN: Adult patients with continuous health plan enrollment for ≥12 months pre- and 3 months post-inpatient PE diagnosis (index date=discharge date) between October 1, 2011-June 30, 2015 and an anticoagulant claim during the index hospitalization were included. MEASURES AND OUTCOMES: Patients scoring 0 points on the simplified Pulmonary Embolism Stratification Index were considered low-risk and were stratified into SOC and rivaroxaban cohorts. Propensity score matching (PSM) was used to compare hospital-acquired complications (HACs), PE-related outcomes (recurrent venous thromboembolism, major bleeding, and death), and healthcare utilization and costs between the rivaroxaban and SOC cohorts. RESULTS: Among 6746 PE patients, 1918 were low-risk; of these, 73 were prescribed rivaroxaban, 1546 were prescribed SOC, and 299 were prescribed other anticoagulants during the index hospitalization. After 1:3 PSM, 64 rivaroxaban and 192 SOC patients were included. During the index hospitalization, rivaroxaban users (versus SOC) had similar inpatient length of stay (LOS; 7.0 vs 6.7 days, standardized difference [STD]=1.8) but fewer HACs (4.7% vs 10.4%; STD: 21.7). In the 90-day post-discharge period, PE-related outcome rates were similar between the cohorts (all p>0.05). However, rivaroxaban users had fewer outpatient (15.9 vs 20.4; p=0.0002) visits per patient as well as lower inpatient ($765 vs $2,655; p<0.0001), pharmacy ($711 vs $1,086; p=0.0033), and total costs ($6,270 vs $9,671; p=0.0027). CONCLUSIONS: LRPE patients prescribed rivaroxaban had similar index LOS and PE-related outcomes, but fewer HACs, and lower total costs than those prescribed SOC.

Effectiveness and safety of rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation and heart failure.

AIMS: Heart failure (HF) is a common co-morbidity in non-valvular atrial fibrillation (NVAF) patients and a potent risk factor for stroke, bleeding, and a decreased time-in-therapeutic range with warfarin. We assessed the real-world effectiveness and safety of rivaroxaban and warfarin in NVAF patients with co-morbid HF. METHODS AND RESULTS: Using US Truven MarketScan Commercial and Medicare supplemental database claims data from 11/2011 to 12/2016, we identified oral anticoagulant (OAC)-naïve NVAF patients with HF (International Classification of Diseases, 10th Revision codes of I50 or I09.81) and ≥12 months of insurance coverage prior to the qualifying OAC dispensing. Rivaroxaban users (20 or 15 mg once daily) were 1:1 propensity score matched to warfarin users, with residual absolute standardized differences <0.1 being achieved for all covariates after matching. Patients were followed up until an event, OAC discontinuation/switch, insurance disenrolment, or end of follow-up. Rates [events per 100 person-years (PYs) of follow-up] for stroke or systemic embolism and major bleeding (using the Cunningham algorithm) were compared between the matched cohorts using Cox proportion hazard regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). We matched 3418 rivaroxaban (32% receiving the reduced dose) and 3418 warfarin users with NVAF and HF with a median (interquartile range) available follow-up of 1.4 (0.6, 2.5) years. Median age was 74 (63, 82) years, and median CHA2 DS2 -VASc and HASBLED scores were 4 (3, 5) and 2 (2, 3). Common HF medications included beta-blockers (64%), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (62%), loop diuretics (46%), digoxin (11%), and aldosterone receptor antagonists (10%). The hazard of developing stroke or systemic embolism (0.98 events/100PY vs. 1.28 events/100PY; HR = 0.82, 95% CI = 0.47-1.44), ischaemic stroke (0.70 events/100PY vs. 1.02 events/100PY; HR = 0.77, 95% CI = 0.41-1.46), or major bleeding (3.86 events/100PY vs. 4.23 events/100PY; HR = 0.98, 95% CI = 0.73-1.31) was not found to be different between rivaroxaban and warfarin users. Intracranial haemorrhage was infrequent in both cohorts and numerically less with rivaroxaban (0.27 events/100PY vs. 0.36 events/100PY; HR = 0.73, 95% CI = 0.25-2.08). CONCLUSIONS: Effectiveness and safety of rivaroxaban vs. warfarin are sustained in NVAF patients with co-morbid HF treated in routine practice. The general consistency between this real-world study and those from phase III randomized trial data of rivaroxaban should provide additional reassurance to clinicians regarding the use of rivaroxaban in NVAF patients with HF.

Ranolazine in patients with type 2 diabetes and chronic angina: A cost-effectiveness analysis and assessment of health-related quality-of-life.

BACKGROUND: Type 2 diabetes (T2D) is associated with a high burden of angina. Ranolazine has been shown to reduce angina frequency versus placebo in patients with T2D and stable angina. We sought to estimate the cost-effectiveness of ranolazine when added to standard-of-care (SoC) versus SoC alone in patients with T2D and stable, but symptomatic coronary disease despite treatment with 1-2 antianginals. METHODS: A Markov model was developed and evaluated using cohort simulation. The model utilized a US societal perspective, 1-month cycle length and 1-year time horizon and was developed to estimate the cost-effectiveness of ranolazine versus SoC. Patients entered the model in 1 of 4 angina frequency health states based on baseline Seattle Angina Questionnaire Angina Frequency scores (100 = no; 61-99 = monthly; 31-60 = weekly; 0-30 = daily) and could transition between health states (first cycle only) or to death (any cycle) based on probabilities derived from the Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina trial. RESULTS: Our model estimated patients treated with ranolazine lived a mean of 0.728 quality adjusted life years (QALYs) at a cost of $16,654. Those not receiving ranolazine lived a mean of 0.702 QALYs and incurred costs of $15,476. The incremental cost-effectiveness ratio for the addition of ranolazine to SoC was $45,308/QALY. Short Form-36 data suggest improvements in patients' bodily pain drove the gain in QALYs associated with ranolazine (2.73 versus 3.96, p = 0.01). CONCLUSION: Our model suggests the addition of ranolazine to SoC is likely cost-effective from a US societal perspective for the treatment of patients with T2D and stable, symptomatic coronary disease despite treatment with 1-2 antianginals.

Effectiveness and safety of rivaroxaban versus warfarin in patients with provoked venous thromboembolism.

A paucity of real-world data evaluating rivaroxaban in provoked venous thromboembolism (VTE) exists. We assessed the effectiveness and safety of rivaroxaban versus warfarin in provoked VTE patients treated in routine practice. Using MarketScan claims data from 1/2012 to 12/2016, we identified adults who had ≥ 1 primary hospitalization/emergency department discharge diagnosis code for VTE (index event) and a provoking factor, received rivaroxaban or warfarin as their first outpatient oral anticoagulant within 30-days of the index event and had ≥ 12-month of insurance coverage prior the index VTE. Provoking factors included cancer, hospital admission for ≥ 3-consecutive days over the prior 3-months, major surgery, trauma or fracture within 90-days or pregnancy within 42-weeks of the index VTE. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weights based on propensity-scores (residual standardized differences < 0.1 achieved for all covariates after adjustment). The incidence of the composite endpoint of recurrent VTE or major bleeding at 3- and 6-months was compared using Cox regression and reported as hazard ratios (HRs) and 95% confidence intervals (CIs). We included 4454 rivaroxaban and 13,164 warfarin users with provoked VTE. At 3- and 6-months, rivaroxaban was associated with a reduced hazard of the composite endpoint (HR 0.72, 95% CI 0.61-0.84 and HR 0.69, 95% CI 0.60-0.80) and recurrent VTE (HR 0.70, 95% CI 0.59-0.84 and HR 0.71, 95% CI 0.60-0.84) versus warfarin. Major bleeding was non-significantly reduced at 3-months (HR 0.77, 95% CI 0.57-1.06) and significantly reduced at 6-months (HR 0.68, 95% CI 0.53-0.88) with rivaroxaban. Rivaroxaban reduces recurrent VTE and major bleeding risk versus warfarin in provoked VTE patients treated in routine practice.

Emergency Department Discharge of Pulmonary Embolus Patients.

BACKGROUND: Hospitalization for low-risk pulmonary embolism (PE) is common, expensive, and of questionable benefit. OBJECTIVE: The objective was to determine if low-risk PE patients discharged from the emergency department (ED) on rivaroxaban require fewer hospital days compared to standard of care (SOC). METHODS: Multicenter, open-label randomized trial in low-risk PE defined by Hestia criteria. Adult subjects were randomized to early ED discharge on rivaroxaban or SOC. Primary outcome was total number of initial hospital hours, plus hours of hospitalization for bleeding or venous thromboembolism (VTE), 30 days after randomization. A 90-day composite safety endpoint was defined as major bleeding, clinically relevant nonmajor bleeding, and mortality. RESULTS: Of 114 randomized subjects, 51 were early discharge and 63 were SOC. Of 112 (98.2%) receiving at least one dose of study drug, 99 (86.8%) completed the study. Initial hospital LOS was 4.8 hours versus 33.6 hours, with a mean difference of -28.8 hours (95% confidence interval [CI] = -42.55 to -15.12 hours) for early discharge versus SOC, respectively. At 90 days, mean total hospital days (for any reason) were less for early discharge than SOC, 19.2 hours versus 43.2 hours, with a mean difference of 26.4 hours (95% CI = -46.97 to -3.34 hours). At 90 days, there were no bleeding events, recurrent VTE, or deaths. The composite safety endpoint was similar in both groups, with a difference in proportions of 0.005 (95% CI = -0.18 to 0.19). Total costs were $1,496 for early discharge and $4,234 for SOC, with a median difference of $2,496 (95% CI = -$2,999 to -$2,151). CONCLUSIONS: Low-risk ED PE patients receiving early discharge on rivaroxaban have similar outcomes to SOC, but fewer total hospital days and lower costs over 30 days.

CMS hospital readmission reduction program and anticoagulants received following a total hip and knee arthroplasty discharge.

OBJECTIVES: To assess association between 30 day readmission rate and treatment received after total hip and knee arthroplasty (THA/TKA) discharge (rivaroxaban vs. warfarin or non-anticoagulant). To subsequently model impact of increasing rivaroxaban use on the Hospital Readmission Reduction Program (HRRP) penalty, which was imposed on hospitals with excess 30 day readmissions after hospitalizations for selected conditions, including THA/TKA. METHODS: The US Truven Health MarketScan Medicare Supplemental database from 1 July 2010 to 30 April 2015 was used. A retrospective claims analysis was conducted to assess the risk of all-cause 30 day readmission among patients receiving either rivaroxaban or warfarin, or no anticoagulation following THA/TKA discharge. Simulations were performed to estimate the impact of post-discharge treatment on the HRRP penalty. RESULTS: The risk-adjusted all-cause 30 day readmission rates were 1.21% (95% confidence interval [95% CI]: 0.94%-1.49%), 1.41% (95% CI: 1.19%-1.58%) and 1.95% (95% CI: 1.81%-2.11%) for rivaroxaban, warfarin and non-anticoagulant cohorts, respectively. Using these rates, simulations illustrated that when switching patients from warfarin or non-anticoagulant to rivaroxaban, annual penalty per hospital would be reduced up to 67% or 88%, respectively. CONCLUSIONS: Rivaroxaban treatment post-THA/TKA discharge reduced the risk of 30 day readmission compared to non-anticoagulants. Simulations illustrated that increasing rivaroxaban use could decrease the HRRP penalty.

The cost of cardiovascular-disease-related death in patients with type 2 diabetes mellitus.

OBJECTIVES: To assess the magnitude of difference in all-cause healthcare resource utilization (HCRU) and costs between patients with type 2 diabetes mellitus (T2DM) who died from a cardiovascular disease (CVD)-related cause in the year preceding death vs. those who did not die during this same period. METHODS: A large US administrative claims database was used to identify patients with T2DM who died of a CVD-related cause from July 2012 to April 2015. These patients were matched 1:1 to patients with T2DM who did not die, using direct matching methods. HCRU and costs were assessed in each of the four quarters (Q4: 12-10 months; Q3: 9-7 months; Q2: 6-4 months; and Q1: 3-0 months) prior to death and compared between patient cohorts using paired t-tests and McNemar's tests. RESULTS: A final matched cohort of 7648 patients who died and 7648 patients who did not die were identified. A significantly higher proportion of patients who died utilized inpatient services vs. those who did not die (Q4: 12.6% vs. 4.6%, p < .001; Q3: 14.6% vs. 4.6%, p < .001; Q2: 17.6% vs. 5.5%, p < .001; and Q1: 65.0% vs. 10.1%, p < .001). In addition, patients who died incurred significantly higher all-cause costs (Q4: $8882 vs. $3970, p < .001; Q3: $10,462 vs. $3661, p < .001; Q2: $12,564 vs. $4169, p < .001; and Q1: $36,076 vs. $6319, p < .001). CONCLUSIONS: T2DM patients with a CVD-related death had significantly greater HCRU and costs in the year including and preceding death compared to those who did not die.

Agreement between coding schemas used to identify bleeding-related hospitalizations in claims analyses of nonvalvular atrial fibrillation patients.

BACKGROUND: Schemas to identify bleeding-related hospitalizations in claims data differ in billing codes used and coding positions allowed. We assessed agreement across bleeding-related hospitalization coding schemas for claims analyses of nonvalvular atrial fibrillation (NVAF) patients on oral anticoagulation (OAC). HYPOTHESIS: We hypothesized that prior coding schemas used to identify bleeding-related hospitalizations in claim database studies would provide varying levels of agreement in incidence rates. METHODS: Within MarketScan data, we identified adults, newly started on OAC for NVAF from January 2012 to June 2015. Billing code schemas developed by Cunningham et al., the US Food and Drug Administration (FDA) Mini-Sentinel program, and Yao et al. were used to identify bleeding-related hospitalizations as a surrogate for major bleeding. Bleeds were subcategorized as intracranial hemorrhage (ICH), gastrointestinal (GI), or other. Schema agreement was assessed by comparing incidence, rates of events/100 person-years (PYs), and Cohen's kappa statistic. RESULTS: We identified 151 738 new-users of OAC with NVAF (CHA2DS2-VASc score = 3, [interquartile range = 2-4] and median HAS-BLED score = 3 [interquartile range = 2-3]). The Cunningham, FDA Mini-Sentinel, and Yao schemas identified any bleeding-related hospitalizations in 1.87% (95% confidence interval [CI]: 1.81-1.94), 2.65% (95% CI: 2.57-2.74), and 4.66% (95% CI: 4.55-4.76) of patients (corresponding rates = 3.45, 4.90, and 8.65 events/100 PYs). Kappa agreement across schemas was weak-to-moderate (κ = 0.47-0.66) for any bleeding hospitalization. Near-perfect agreement (κ = 0.99) was observed with the FDA Mini-Sentinel and Yao schemas for ICH-related hospitalizations, but agreement was weak when comparing Cunningham to FDA Mini-Sentinel or Yao (κ = 0.52-0.53). FDA Mini-Sentinel and Yao agreement was moderate (κ = 0.62) for GI bleeding, but agreement was weak when comparing Cunningham to FDA Mini-Sentinel or Yao (κ = 0.44-0.56). For other bleeds, agreement across schemas was minimal (κ = 0.14-0.38). CONCLUSIONS: We observed varying levels of agreement among 3 bleeding-related hospitalizations schemas in NVAF patients.

Implications of stroke and bleeding risk scores and comorbidities on episode-based bundled payments for patients with nonvalvular atrial fibrillation.

OBJECTIVES: Due to the high cost of nonvalvular atrial fibrillation (NVAF), this condition may be a suitable candidate for condition-specific bundled payments. This paper evaluates the healthcare cost of NVAF and uses common bleeding and stroke risk scores (HAS-BLED and CHA2DS2-VASc) to explore the risk-based healthcare cost differences among NVAF patients. METHODS: MarketScan claims of NVAF patients (ICD-9-CM code 427.31) were analyzed from January 2010 to April 2015. These claims feature more than 196 million covered lives and more than 300 contributing employers and 25 contributing health plans. A retrospective cohort design was used to assess episodes of care costs among patients with NVAF. Previously and newly diagnosed NVAF patients were selected from adult patients with ≥2 diagnoses of NVAF, and without valvular disease. Total all-cause healthcare costs at 1 year were stratified by stroke (CHA2DS2-VASc) and bleeding (HAS-BLED) risk scores. Study data was extracted in the MarketScan Commercial Claims and Encounters Database (Commercial Database) and the MarketScan Medicare Supplemental and Coordination of Benefits Database (Medicare Supplemental Database). RESULTS: Mean all-cause 1 year cost of care based on stroke risk (CHA2DS2-VASc) varied from $15,703 to $59,163 for previously diagnosed and $25,992 to $62,458 for newly diagnosed NVAF. Similarly, mean cost varied base on bleeding risk (HAS-BLED) for previously and newly diagnosed NVAF from $17,950 to $57,029 and $26,356 to $67,104 respectively. CONCLUSION: NVAF patients accrue variable healthcare costs. Stroke and bleeding risk should be taken into account during the creation of NVAF payment bundles.

Cost-utility of empagliflozin in patients with type 2 diabetes at high cardiovascular risk.

AIMS: In the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG) trial, empagliflozin reduced cardiovascular and all-cause mortality in type 2 diabetes (T2D) patients at high cardiovascular risk. We sought to estimate the cost-effectiveness of empagliflozin versus standard treatment for the prevention of cardiovascular morbidity and mortality in patients with T2D. METHODS: A Markov model was developed to assess the cost-effectiveness of empagliflozin (versus standard treatment) for the prevention of cardiovascular morbidity and mortality in patients with T2D using a 3-month cycle length and a lifetime horizon. Data sources included the EMPA-REG randomized clinical trial and other published epidemiological studies. Outcomes included treatment costs (in 2016 US$), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Probabilistic sensitivity analysis (PSA) was performed to test the robustness of conclusions. RESULTS: Empagliflozin use resulted in higher total lifetime treatment costs ($371,450 versus $272,966) but yielded greater QALYs (10.712 vs. 9.419) compared to standard treatment. This corresponded to an ICER of $76,167 per QALY gained. PSA suggested empagliflozin would be cost-effective in 96% of 10,000 iterations assuming a willingness-to-pay threshold of $100,000 per QALY gained. CONCLUSION: Empagliflozin may be cost-effective compared to standard treatment in T2D patients at high cardiovascular risk.