Switching to Another Oral Anticoagulant and Drug Discontinuation Among Elderly Patients With Nonvalvular Atrial Fibrillation Treated With Different Direct Oral Anticoagulants.

We compared the risks of switching to another oral anticoagulant (OAC) and discontinuation of direct oral anticoagulants (DOACs) among elderly patients with nonvalvular atrial fibrillation (NVAF) who were prescribed rivaroxaban or dabigatran versus apixaban. Patients (≥65 years of age) with NVAF prescribed DOACs (January 1, 2013 to September 30, 2017) were identified from the Humana research database and grouped into DOAC cohorts. Cox regression analyses were used to evaluate whether the risk for switching to another OAC or discontinuing index DOACs differed among cohorts. Of the study population (N = 38 250), 55.9% were prescribed apixaban (mean age: 78.6 years; 49.8% female), 37.3% rivaroxaban (mean age: 77.4 years; 46.7% female), and 6.8% dabigatran (mean age: 77.0 years; 44.0% female). Compared to patients prescribed apixaban, patients prescribed rivaroxaban (hazard ratio [HR]: 2.08; 95% confidence interval [CI], 1.92-2.25; P < .001) or dabigatran (HR: 3.74; 95% CI, 3.35-4.18, P < .001) had a significantly higher risk of switching to another OAC during the follow-up; compared to patients prescribed apixaban, the risks of discontinuation were also higher for patients treated with rivaroxaban (HR: 1.10; 95% CI, 1.07-1.13, P < .001) or dabigatran (HR: 1.29; 95% CI, 1.23-1.35, P < .001).

Comparison of Drug Switching and Discontinuation Rates in Patients with Nonvalvular Atrial Fibrillation Treated with Direct Oral Anticoagulants in the United States.

INTRODUCTION: Continuous usage of direct oral anticoagulants (DOACs) among nonvalvular atrial fibrillation (NVAF) patients is essential to maintain stroke prevention. We examined switching and discontinuation rates for the three most frequently initiated DOACs in NVAF patients in the USA. METHODS: Patients who initiated apixaban, rivaroxaban, or dabigatran (index event/date) were identified from the Pharmetrics Plus claims database (Jan 1, 2013-Sep 30, 2016, includes patients with commercial and Medicare coverage) and grouped into cohorts by index DOAC. Patients were required to have a diagnosis of NVAF and continuous health plan enrollment for 12 months prior to the index date (baseline period) and at least 3 months during the follow-up period. Drug switching rates to any other DOAC or warfarin and index DOAC discontinuation rate were evaluated separately with descriptive statistics, Kaplan-Meier analysis, and multivariable Cox regression analysis. RESULTS: Of the NVAF study population (n = 41,864), 37% initiated apixaban (n = 15,352; mean age 62 years), 51% initiated rivaroxaban (n = 21,250; mean age 61 years), and 13% initiated dabigatran (n = 5262; mean age 61 years). During the follow-up period, the unadjusted drug switching rates of patients treated with apixaban, rivaroxaban, and dabigatran were 3.6%, 6.3%, and 11.1%, respectively (p < 0.001 across the three cohorts); while the index DOAC discontinuation rates were 52.8%, 60.3%, and 62.9%, respectively (p < 0.001). After we controlled for differences in patient characteristics, patients treated with rivaroxaban (HR 1.8; 95% CI 1.6-2.0; p < 0.001) and dabigatran (HR 3.4; 95% CI 3.0-3.8, p < 0.001) had a significantly greater likelihood for drug switching than patients treated with apixaban. Also, both rivaroxaban (HR 1.1; 95% CI 1.1-1.2, p < 0.001) and dabigatran (HR 1.3; 95% CI 1.2-1.3, p < 0.001) treated patients were more likely to discontinue treatment. CONCLUSION: In the real-world setting, patients with NVAF newly treated with apixaban were less likely to switch or discontinue treatment compared to patients treated with rivaroxaban or dabigatran. FUNDING: Pfizer and Bristol-Myers Squibb.

Economic value of regular monitoring of response to treatment among US patients with chronic myeloid leukemia based on an economic model.

BACKGROUND: Regular molecular monitoring with reverse-transcription quantitative PCR (RT-qPCR) analysis of BCR-ABL1 transcripts is associated with reduced disease progression among patients with chronic myeloid leukemia (CML). Molecular monitoring assists in the timely detection of primary or secondary resistance to tyrosine kinase inhibitor (TKI) therapy and is a recommended practice by the National Comprehensive Cancer Network guidelines. An economic model was developed to estimate the potential impact of CML monitoring vs lack of monitoring on patient healthcare costs. METHODS: An Excel-based decision-analytic economic model was developed from a US payer perspective. The model was used to estimate the expected healthcare cost differences between regular molecular monitoring of CML patients and lack of monitoring. CML progression rates among patients with vs without monitoring, the annual cost of CML progression, the average number of monitoring tests per year, and the average cost per RT-qPCR monitoring test were incorporated into the model. Univariate and multivariable sensitivity analyses were conducted. RESULTS: Based on estimates in published literature, disease progression to the accelerated/blast phase occurs among 0.35% of patients with monitoring and 5.12% of patients without monitoring, and the annual cost of CML progression is $136,308 per patient year. The analysis found that total healthcare costs, including the costs associated with CML progression and RT-qPCR monitoring tests (three tests per year), were $1,142 for patients with monitoring and $6,982 for patients without monitoring (difference = $5,840). In a hypothetical cohort of 100 patients with CML, achieving a 100% monitoring rate was associated with a total cost-savings of $584,005 compared to a 0% monitoring rate. This cost-savings remained consistent under both univariate and multivariable sensitivity analyses. CONCLUSION: Regular CML monitoring was associated with improved outcomes among CML patients and, consequently, reduced healthcare costs.

Comparison of effectiveness and safety of treatment with apixaban vs. other oral anticoagulants among elderly nonvalvular atrial fibrillation patients.

OBJECTIVE: To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) of elderly (≥65 years of age) nonvalvular atrial fibrillation (NVAF) patients initiating apixaban vs. rivaroxaban, dabigatran, or warfarin. METHODS: NVAF patients with Medicare Advantage coverage in the US initiating oral anticoagulants (OACs, index event) were identified from the Humana database (1 January 2013-30 September 2015) and grouped into cohorts depending on OAC initiated. Propensity score matching (PSM), 1:1, was conducted among patients treated with apixaban vs. each other OAC, separately. Rates of S/SE and MB were evaluated in the follow-up. Cox regressions were used to compare the risk of S/SE and MB between apixaban and each of the other OACs during the follow-up. RESULTS: The matched pairs of apixaban vs. rivaroxaban (n = 13,620), apixaban vs. dabigatran (n = 4654), and apixaban vs. warfarin (n = 14,214) were well balanced for key patient characteristics. Adjusted risks for S/SE (hazard ratio [HR] vs. rivaroxaban: 0.72, p = .003; vs. warfarin: 0.65, p < .001) and MB (HR vs. rivaroxaban: 0.49, p < .001; vs. warfarin: 0.53, p < .001) were significantly lower during the follow-up for patients treated with apixaban vs. rivaroxaban and warfarin. Adjusted risks for S/SE (HR: 0.78, p = .27) and MB (HR: 0.82, p = .23) of NVAF patients treated with apixaban vs. dabigatran trended to be lower, but did not reach statistical significance. CONCLUSIONS: In the real-world setting after controlling for differences in patient characteristics, apixaban is associated with significantly lower risk of S/SE and MB than rivaroxaban and warfarin, and a trend towards better outcomes vs. dabigatran among elderly NVAF patients in the US.

Major bleeding risk and healthcare economic outcomes of non-valvular atrial fibrillation patients newly-initiated with oral anticoagulant therapy in the real-world setting.

AIMS: This study compared the risk for major bleeding (MB) and healthcare economic outcomes of patients with non-valvular atrial fibrillation (NVAF) after initiating treatment with apixaban vs rivaroxaban, dabigatran, or warfarin. METHODS: NVAF patients who initiated apixaban, rivaroxaban, dabigatran, or warfarin were identified from the IMS Pharmetrics Plus database (January 1, 2013-September 30, 2015). Propensity score matching (PSM) was used to balance differences in patient characteristics between study cohorts: patients treated with apixaban vs rivaroxaban, apixaban vs dabigatran, and apixaban vs warfarin. Risk of hospitalization and healthcare costs (all-cause and MB-related) were compared between matched cohorts during the follow-up. RESULTS: During the follow-up, risks for all-cause (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.2-1.7) and MB-related (HR = 1.57, 95% CI = 1.0-2.4) hospitalizations were significantly greater for patients treated with rivaroxaban vs apixaban. Adjusted total all-cause healthcare costs were significantly lower for patients treated with apixaban vs rivaroxaban ($3,950 vs $4,333 per patient per month [PPPM], p = .002) and MB-related medical costs were not statistically significantly different ($100 vs $233 PPPM, p = .096). Risk for all-cause hospitalization (HR = 1.98, 95% CI = 1.6-2.4) was significantly greater for patients treated with dabigatran vs apixaban, although total all-cause healthcare costs were not statistically different. Risks for all-cause (HR = 2.22, 95% CI = 1.9-2.5) and MB-related (HR = 2.05, 95% CI = 1.4-3.0) hospitalizations were significantly greater for patients treated with warfarin vs apixaban. Total all-cause healthcare costs ($3,919 vs $4,177 PPPM, p = .025) and MB-related medical costs ($96 vs $212 PPPM, p = .026) were significantly lower for patients treated with apixaban vs warfarin. LIMITATIONS: This retrospective database analysis does not establish causation. CONCLUSIONS: In the real-world setting, compared with rivaroxaban and warfarin, apixaban is associated with reduced risk of hospitalization and lower healthcare costs. Compared with dabigatran, apixaban is associated with lower risk of hospitalizations.

Use of Real-World Claim Databases to Assess Prevalence of Comorbid Conditions Relevant to the Treatment of Chronic Myelogenous Leukemia Based on National Comprehensive Network Treatment Guidelines.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines state that based on toxicity profiles, 1 second-generation tyrosine kinase inhibitor (TKI) indicated for first-line therapy (ie, dasatinib, nilotinib) may be preferred over the other for treatment of chronic myelogenous leukemia (CML) patients with certain comorbidities. This study assessed the prevalence of comorbid conditions relevant to TKI treatment choice among CML patients in the US real-world setting. PATIENTS AND METHODS: Patients who had CML and initiated TKI treatment were identified from the MarketScan Commercial and Medicare databases (January 1, 2006, to June 30, 2013). Demographics and prevalence of comorbid conditions relevant to TKI treatment choice per NCCN guidelines (heart disease, arrhythmia, diabetes, pancreatitis, pleural effusion, lung disease) were assessed among the overall study population and among subgroups. RESULTS: The median age of the CML study population newly initiated on TKI treatment (ie, imatinib, dasatinib, or nilotinib; n = 2296) was 56 years. Approximately 41% of the CML study population had at least 1 comorbid condition that may influence the choice of TKI treatment as recommended by NCCN guidelines. The most prevalent comorbid condition was heart disease (23%), followed by diabetes (18%) and lung disease (13%). The prevalence of comorbid conditions relevant to TKI treatment choice varied among patients of different age groups, gender, and US regions. CONCLUSION: The results of this analysis provide real-world evidence that the prevalence of relevant comorbid conditions is substantial among CML patients in the US managed care setting and therefore needs to be considered throughout various health care decision-making processes related to CML.

Comparison of differences in medical costs when new oral anticoagulants are used for the treatment of patients with non-valvular atrial fibrillation and venous thromboembolism vs warfarin or placebo in the US.

OBJECTIVE: Medical costs that may be avoided when any of the four new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, are used instead of warfarin for the treatment of non-valvular atrial fibrillation (NVAF) were estimated and compared. Additionally, the overall differences in medical costs were estimated for NVAF and venous thromboembolism (VTE) patient populations combined. METHODS: Medical cost differences associated with NOAC use vs warfarin or placebo among NVAF and VTE patients were estimated based on clinical event rates obtained from the published trial data. The clinical event rates were calculated as the percentage of patients with each of the clinical events during the trial periods. Univariate and multivariate sensitivity analyses were conducted for the medical-cost differences determined for NVAF patients. A hypothetical health plan population of 1 million members was used to estimate and compare the combined medical-cost differences of the NVAF and VTE populations and were projected in the years 2015-2018. RESULTS: In a year, the medical-cost differences associated with NOAC use instead of warfarin were estimated at -$204, -$140, -$495, and -$340 per patient for dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. In 2014, among the hypothetical population, the medical-cost differences were -$3.7, -$4.2, -$11.5, and -$6.6 million for NVAF and acute VTE patients treated with dabigatran, rivaroxaban, apixaban, and edoxaban, respectively. In 2014, for the combined NVAF, acute VTE, and extended VTE patient populations, medical-cost differences were -$10.0, -$10.9, -$21.0, and -$21.0 million for dabigatran, rivaroxaban, 2.5 mg apixaban, and 5 mg apixaban, respectively. Medical-cost differences associated with use of NOACs were projected to steadily increase from 2014 to 2018. CONCLUSIONS: Medical costs are reduced when NOACs are used instead of warfarin/placebo for the treatment of NVAF or VTE, with apixaban being associated with the greatest reduction in medical costs.

Increased risk of venous thromboembolic events with corticosteroid vs biologic therapy for inflammatory bowel disease.

BACKGROUND & AIMS: We investigated whether treatment of active inflammatory bowel disease with biologic agents is associated with a reduced risk of venous thromboembolic events (VTEs) compared with corticosteroid therapy. METHODS: We performed a retrospective analysis of 15,100 adults with inflammatory bowel disease who were identified from the Truven Health MarketScan databases. We analyzed data from patients who received 6 months of continuous medical and prescription coverage before and 12 months after their first diagnosis and had no VTE during the 6 months before they first received biologic or corticosteroid therapy. The outcome assessed was any VTE that occurred during the 12-month follow-up period. A multivariate logistic regression model was used to evaluate the effects of biologic, corticosteroid, and combination therapies (biologics and corticosteroids) on VTE risk. RESULTS: Three hundred twenty-five VTEs occurred during the study period (in 2.25% of patients receiving only corticosteroids, in 0.44% of patients receiving biologics, and in 2.49% of patients receiving combination therapy). Compared with patients receiving only corticosteroids, the odds ratio for VTE in patients receiving only biologics was 0.21 (95% confidence interval, 0.05-0.87) in the multivariate model, and the odds ratio for VTE in patients on combination therapy was 1.01. CONCLUSIONS: Compared with treatment with only a biologic agent, corticosteroid therapy is associated with a nearly 5-fold increase in risk for VTE. Combination therapy with corticosteroids and biologic agents was associated with the same risk for VTE as that of corticosteroids alone. Corticosteroids therefore appear to increase risk for VTE.

Evaluation of medical costs associated with use of new oral anticoagulants compared with standard therapy among venous thromboembolism patients.

OBJECTIVE: This study evaluated differences in medical costs associated with clinical end-points from randomized clinical trials that compared the new oral anticoagulants (NOACs), dabigatran, rivaroxaban, apixaban, and edoxaban, to standard therapy for treatment of patients with venous thromboembolism (VTE). RESEARCH DESIGN AND METHODS: Event rates of efficacy and safety end-points from the clinical trials (RE-COVER, RE-COVER II, EINSTEIN-Pooled, AMPLIFY, Hokusai-VTE trial) were obtained from published literature. Incremental annual medical costs among patients with clinical events from a US payer perspective were obtained from the literature or healthcare claims databases and inflation adjusted to 2013 costs. Differences in total medical costs associated with clinical end-points for the NOACs vs standard therapy were then estimated. One-way and Monte Carlo sensitivity analyses were carried out. RESULTS: A lower rate of major bleedings was associated with use of any of the NOACs vs standard therapy. Except for dabigatran, use of NOACs was also associated with a lower rate of recurrent VTE/death. As a result of the reduction in clinical event rates, the overall medical cost differences were -$146, -$482, -$918, and -$344 for VTE patients treated with dabigatran, rivaroxaban, apixaban, and edoxaban, respectively, vs patients treated with standard therapy. CONCLUSIONS: When any of the four NOACs are used instead of standard therapy for acute VTE, treatment medical costs are reduced. Apixaban is associated with the greatest reduction in medical costs, which is driven by medical cost reductions associated with both efficacy and safety end-points. Further evaluation may be needed to validate these results in the real-world setting.

Warfarin therapy in patients with venous thromboembolism: patterns of use and predictors of clinical outcomes.

INTRODUCTION: Few studies have investigated current practices in the USA relating to warfarin use and monitoring, or the effects of warfarin discontinuation on risk of venous thromboembolism (VTE) and bleeding complications. This study investigated the effect of warfarin discontinuation on rates of VTE recurrence in a real-world setting. METHODS: Integrated Healthcare Information Services database records from January 2003 to September 2007 from patients aged at least 18 years, hospitalized for VTE, and with at least two prescriptions or 60 days of warfarin treatment were reviewed, with warfarin discontinuation and international normalized ratio (INR) data collated. RESULTS: A total of 1027 of 8380 (12.3%) patients discontinued warfarin within 3 months. Overall, 1656 (19.8%) patients had no INR monitoring, with 38.1% of INR values being inside the therapeutic range (INR 2-3). Recurrent VTE was observed in 915 (10.9%) patients. Significant predictors of recurrent VTE (at any time) included discontinuation of warfarin within 3 months, time from index VTE to warfarin initiation, previous VTE-related hospitalization, and duration of index hospitalization. CONCLUSION: This study found that in a real-world population, less than 50% of warfarin patients achieved INR values within the therapeutic range. Warfarin discontinuation within 3 months was associated with a higher rate of recurrent VTE.

Cost of atrial fibrillation in United States managed care organizations.

INTRODUCTION: Atrial fibrillation (AF) has been shown to be associated with high healthcare costs; however, limited data are available from large-scale studies quantifying the overall cost burden of AF in the USA. We therefore aimed to provide an up to date estimate of the overall per-patient costs of AF in managed care organizations across the USA. METHODS: This retrospective cohort study used claims data from the Integrated Healthcare Information Systems National Managed Care Benchmark Database from January 2005 to December 2006. Patients included in the analysis were aged > or =20 years and had at least two outpatient AF-related claims without hospitalization, or a hospitalization with a primary or secondary discharge diagnosis of AF in 2005. AF-related inpatient and outpatient costs over 12 months from the initial outpatient claim or first hospitalization were examined. For secondary AF hospitalizations, incremental costs associated with AF were measured by comparing costs for patients with AF with a group of matched controls hospitalized without AF. RESULTS: In total, 35,255 patients diagnosed as having AF (5008 with a primary AF diagnosis, 10,776 with a secondary AF diagnosis, 19,471 with outpatient-managed AF), and 20,571 controls without AF, were included in the analysis. Over 12 months, for primary AF hospitalization patients, inpatient costs were $11,306.53 and outpatient costs were $2826.78 (total $14,133.30) per patient. For hospitalized patients with secondary AF, incremental AF-related inpatient costs were $5181.19 and outpatient costs were $1376.33 (total $6557.52). For AF patients with outpatient management in 2005, 12-month AF-related costs were $2177.30 ($175.47 for AF hospitalizations in 2006 and $2001.85 for outpatient costs). CONCLUSIONS: Overall costs of AF in the US managed care organizations are high. Costs are primarily due to inpatient expenses. Improved disease management strategies to reduce AF-related hospitalizations and decrease the overall cost burden of AF are needed.

National assessment of Medicare prescription plan coverage gaps among patients with atrial fibrillation in the US.

INTRODUCTION: The Medicare Part D prescription plan has a coverage gap from $2250 to $5100 per year (2006 thresholds) in which patients pay full drug costs (the "donut hole"). We examined prescription costs in patients aged >or=65 years with atrial fibrillation (AF), and the proportions entering/exiting the donut hole in 2006. METHODS: This retrospective cohort study used claims data from the Integrated Healthcare Information Systems National Managed Care Benchmark Database from January 2005 to December 2006. Medicare Advantage patients aged >or=65 years who were hospitalized with a primary/secondary discharge diagnosis of AF, or had >or=2 outpatient AF claims without hospitalization in 2005, were identified. Total 2006 prescription costs were calculated by summing health plan payments and patient copayments. RESULTS: Of 16,655 patients included in the analysis, 1527 were hospitalized with a primary AF diagnosis, 6067 with a secondary AF diagnosis, and 9061 had outpatient-managed AF in 2005. Mean 2006 per-patient prescription costs were $3457.16. In total, 58.8% of patients reached the $2250 threshold in a mean of 199 days; including 59.9% of primary AF hospitalization, 63.5% of secondary AF hospitalization, and 55.5% of patients with outpatient-managed AF. Of the overall population, 21.2% reached the $5100 threshold in a mean of 257 days; including 21.3% of primary AF hospitalization, 27.3% of secondary AF hospitalization, and 17.2% of patients with outpatient-managed AF. AF-related drugs accounted for only 15% of the total prescription costs, with the majority of costs relating to the treatment of non-AF comorbidities. CONCLUSIONS: In 2006, total annual prescription costs in this population of Medicare Advantage AF patients were considerable. In this sample population, over half of patients would have had prescription costs in excess of the 2006 Part D donut hole threshold. The costs of AF treatment itself were relatively low, with the majority of prescription costs relating to the treatment of non-AF comorbidities.

Direct medical costs of venous thromboembolism and subsequent hospital readmission rates: an administrative claims analysis from 30 managed care organizations.

BACKGROUND: Venous thromboembolism (VTE) is a common medical condition manifested as deep vein thrombosis (DVT) or pulmonary embolism (PE). Few data exist on the total economic burden of DVT and PE. OBJECTIVE: To (1) quantify the economic burden of DVT and PE in direct medical costs and utilization and (2) determine the rates of hospital readmission for DVT and PE. METHODS: Hospital claims containing DVT or PE as a primary or secondary discharge diagnosis during the period February 1998 through June 2004 were identified by retrospective analysis using the Integrated Health Care Information Services (IHCIS) National Managed Care Database. For the cost analysis, we included patients that had been enrolled in a health care plan for a minimum of 30 days prior to and 365 days following the DVT or PE hospitalization. For the readmission analysis, patients were required to have a minimum length of stay of 3 days and a pre-enrollment of 365 days. We quantified the cost burden to the health plan by examining annual DVT- and PE-related payments made by the health plan to providers for inpatient and outpatient care. RESULTS: Of 5 million plus discharges in the database with dates of service between February 1, 1998, and June 30, 2004, 32,193 (0.64%) had DVT or PE as a primary discharge diagnosis, and 26,159 (0.52%) had DVT or PE as a secondary discharge diagnosis. After application of the inclusion and exclusion criteria, there were 5,348 patients with a primary discharge diagnosis of DVT and 4,593 patients with a secondary discharge diagnosis of DVT. For PE, 2,984 patients had a primary discharge diagnosis, and 1,119 had a secondary discharge diagnosis. The hospital readmission rates within 1 year for the combined diagnoses (DVT or PE) were 5.3% for primary and 14.3% for secondary diagnoses; 44.3% of the PE readmissions occurred within the first 30 days. Within 90 days, 50.7% of DVT readmissions and 58.6% of PE readmissions occurred. Regarding cost for a primary diagnosis, the average total annual provider payments made by a health plan were $10,804 for DVT and $16,644 for PE. For secondary diagnoses, the average total annual costs were $7,594 for DVT and $13,018 for PE. The mean hospital cost per readmission for a recurrent DVT ($11,862) was higher than the mean cost for the initial hospitalization ($9,805, P=0.006), but the mean cost per PE readmission ($14,722) was similar to the mean cost for the initial hospitalization ($14,146, P =0.38). CONCLUSIONS: The economic burden of DVT and PE in direct medical cost is large, due not only to the initial hospitalization event, but also to the high rate of hospital readmission (5%-14%), over half of which occurs within 90 days.