Real-world treatment patterns, healthcare resource utilization, and cost among adults with pulmonary arterial hypertension in the United States.

Treatment for pulmonary arterial hypertension (PAH) has evolved over the past decade, including approval of new medications and growing evidence to support earlier use of combination therapy. Despite these changes, few studies have assessed real-world treatment patterns, healthcare resource utilization (HCRU), and costs among people with PAH using recent data. We conducted a retrospective cohort study using administrative claims from the HealthCore Integrated Research Database®. Adult members with claims for a PAH diagnosis, right heart catheterization, and who initiated PAH treatment (index date) between October 1, 2015 and November 30, 2020 were identified. Members had to be continuously enrolled in the health plan for 6 months before the index date (baseline) and ≥30 days after. Treatment patterns, HCRU, and costs were described. A total of 843 members with PAH (mean age 62.3 years, 64.2% female) were included. Only 21.0% of members received combination therapy as their first-line treatment, while most members (54.6%) received combination therapy as second-line treatment. All-cause HCRU remained high after treatment initiation with 58.0% of members having ≥1 hospitalization and 41.3% with ≥1 emergency room visit. Total all-cause costs declined from $15,117 per patient per month at baseline to $14,201 after treatment initiation, with decreased medical costs ($14,208 vs. $6,349) more than offsetting increased pharmacy costs ($909 vs. $7,852). In summary, despite growing evidence supporting combination therapy, most members with PAH initiated treatment with monotherapy. Total costs decreased following treatment, driven by a reduction in medical costs even with increases in pharmacy costs.

How Assessment-Schedule Matching Limits Bias When Comparing Progression-Free Survival in Single-Arm Studies: An Application in Second-Line Urothelial Carcinoma Treatments.

OBJECTIVES: Population-adjusted comparisons of progression-free survival (PFS) from single-arm trials of cancer treatments can be derived using matching-adjusted indirect comparisons (MAICs); however, results are still susceptible to bias, particularly if the trials had different tumor assessment schedules. This study aims to assess the effects of assessment-schedule matching (ASM) on the relative effectiveness on the PFS of avelumab versus approved comparator immunotherapies or chemotherapy after population matching in the second-line (2L) setting for metastatic urothelial carcinoma. METHODS: The MAIC used patient-level data for avelumab from the JAVELIN Solid Tumor trial (NCT01772004). PFS was compared with published curves for other treatments to obtain population-adjusted hazard ratios (HRs). The MAIC was repeated after conducting ASM for differences in tumor assessment scheduled first at 6 weeks for avelumab and durvalumab and at 8 or 9 weeks for other treatments. RESULTS: MAIC adjustment alone altered the HR estimates up to 23%, whereas MAIC plus ASM resulted in up to 32.7% reductions from naive comparisons. Even in cases in which MAIC had little effect, ASM brought an additional change of 11.1% to 15.4%. Overall, the HR range of avelumab versus other treatments changed from 0.83 to 1.25 for naive comparisons to 0.76 to 0.99 after ASM plus MAIC, numerically favoring avelumab. CONCLUSIONS: Small variations in assessment schedules can introduce bias in unanchored indirect treatment comparisons of interval-censored time-to-event outcomes. In this study, adjusted PFS was comparable across second-line urothelial carcinoma treatment options, numerically favoring avelumab versus immunotherapies and chemotherapy agents. Correcting this bias is especially important when HRs are applied in cost-effectiveness models to transition patients between states.

Real-World Clinical and Economic Outcomes in Selected Immune-Related Adverse Events Among Patients with Cancer Receiving Immune Checkpoint Inhibitors.

BACKGROUND: With increased use of immune checkpoint inhibitors (ICIs) among patients with cancer, there is substantial interest in understanding clinical and economic outcomes and management of immune-related adverse events (irAEs). PATIENTS, MATERIALS, AND METHODS: A retrospective study was conducted using Premier Healthcare Database, a U.S. national hospital discharge database, from March 1, 2015, through December 31, 2017. The database comprises more than 880 million inpatient and hospital-based outpatient encounters, with more than 200 million unique patients reported by 966 hospitals. Patients with four solid tumors known to benefit from ICI therapy were included. The list of irAEs assessed was defined a priori per American Society of Clinical Oncology clinical guidelines for irAE management. Baseline irAE-related inpatient and outpatient visits were defined as the first inpatient or hospital-based outpatient visit with discharge diagnosis of any irAE of interest following confirmed ICI usage within 90 days prior to the baseline visit. Patients were followed for 90 days after baseline irAE-related inpatient discharge date or outpatient visit date to assess irAE-related inpatient admissions, all-cause in-hospital mortality, ICI reinitiation, and to determine costs and health care resource utilization. RESULTS: Records from 673,957 patients with four tumor types were reviewed for ICI therapy. Of 13,030 patients receiving ICIs, approximately 40% experienced at least one irAE, with a total of 10,121 irAEs occurring within 90 days of the ICI visit. The most frequent (>1,000 events) irAEs were anemia, impaired ventricular function with heart failure and vasculitis, thrombocytopenia, thyroid conditions, and peripheral edema. As might be expected, compared with those with baseline irAE-related outpatient visits, patients with baseline irAE-related inpatient visits had a significantly higher percentage of irAE-related inpatient admissions (23% vs. 14%) and all-cause in-hospital mortality (22% vs. 6%) and lower reinitiation of ICI therapy (31% vs. 71%). Baseline irAE-related inpatient visits had significantly higher mean costs ($29,477 vs. $5,718) with longer hospital stays (12.6 vs. 7.8 days). CONCLUSION: Findings from a U.S. national hospital discharge database suggest that irAEs in patients treated with ICIs are common, occur in multiples and with greater frequency in those with pre-existing comorbidities. Those with inpatient admissions have poorer outcomes. IMPLICATIONS FOR PRACTICE: The present work addressed the knowledge gap in understanding real-world outcomes of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs). Patients who experienced irAEs had significantly higher baseline comorbidities and were more likely to have immune-related or immune-compromised comorbid conditions. Patients with baseline irAE-related hospitalizations were more likely to be rehospitalized and to experience in-hospital mortality and less likely to reinitiate ICI treatment. Real-world patients are more diverse than clinical trials, and clinicians should consider both the efficacy and safety profile of ICI treatments, especially for patients with comorbidity conditions. Close monitoring is needed after patients have experienced an irAE.

Clinical Outcomes, Costs, and Healthcare Resource Utilization in Patients with Metastatic Merkel Cell Carcinoma Treated with Immune Checkpoint Inhibitors vs Chemotherapy.

PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with poor prognosis. This study compared patient characteristics, comorbidities, adverse events (AEs), treatment persistence, healthcare resource utilization (HRU) and costs in patients with metastatic MCC (mMCC) treated with immune checkpoint inhibitors (ICIs) or recommended chemotherapy per 2018 National Comprehensive Cancer Network (NCCN) Guidelines. PATIENTS AND METHODS: A retrospective, observational study was conducted using data from 3/1/2015 through 12/31/2017 from the Premier Healthcare Database, a US hospital discharge database. The study included patients aged ≥12 years with International Classification of Diseases Codes for MCC and metastasis, categorized by their first treatment (index) during the study period (ICI or NCCN-recommended chemotherapy [chemotherapy]). Patient, hospital, and visit characteristics were assessed at the index date and Charlson Comorbidity Index (CCI) score and comorbidities during a 6-month look-back period. Clinical outcomes, including AEs and treatment persistence were assessed over 90 days and HRU and costs over 180 days post-index. RESULTS: Of 75 patients with mMCC receiving ICIs (n=37) or chemotherapy (n=38), mean age was ≈73 years, and 21.3% had a history of immune-related (IR) conditions. Overall, ICI- and chemotherapy-treated patients were similar in most baseline characteristics, IR comorbidities, and CCI score. However, more ICI patients (46%) than chemotherapy patients (26%) persisted on treatment over 90-day follow-up, odds ratio (95% CI): 2.04 (0.93, 4.47), P=0.07. Over 180-day follow-up, 33% of patients had an inpatient admission with mean length of stay (LOS) ≈2 days shorter for ICI vs chemotherapy (not statistically significant). Total costs, primarily driven by pharmacy costs, were higher for ICIs than chemotherapy; other departmental costs were similar between treatment groups. CONCLUSION: In a real-world setting, patients with mMCC receiving ICIs had higher treatment persistence over 90 days, shorter inpatient LOS and similar departmental cost (excluding pharmacy cost) than those receiving chemotherapy.

Real-world outcomes among US Merkel cell carcinoma patients initiating immune checkpoint inhibitors or chemotherapy.

Aim: Retrospectively assessed treatment patterns and clinical and economic outcomes in Merkel cell carcinoma (MCC) patients receiving recommended first-line regimens. Materials & methods: MCC patients newly treated with either immune checkpoint inhibitors (ICIs) or chemotherapies (CTs) were selected from the Veterans Health Administration database (2013-2018); 74 patients (ICIs: 20 and CTs: 54) were selected. Results: Median duration of therapy was 300 days for ICIs and 91 days for CTs. Time to next treatment was 245 and 184 days, respectively. Mean total (per patient per month) costs were $15,306 (ICIs) and $10,957 (CTs), of which 51% and 86%, respectively, were non-MCC therapy-related costs. Conclusion: Despite higher costs, utilization of ICIs in first-line MCC shows clinical advantages over CTs in the real world.

Budget Impact Of Including Avelumab As A Second-Line Treatment For Locally Advanced Or Metastatic Urothelial Cancer In The United States: Commercial And Medicare Payer Perspectives.

OBJECTIVE: To estimate the budget impact of introducing avelumab as a second-line (2L) treatment option for patients with locally advanced or metastatic urothelial cancer (mUC) from the perspective of a US third-party payer (commercial and Medicare). METHODS: A budget impact model (BIM) with a three-year time horizon was developed for avelumab. Efficacy and safety data were sourced from published literature and US package inserts. The analysis was conducted in collaboration with a specialist oncologist who validated clinical assumptions. Costs were based on the number of eligible patients, time-to-treatment failure, overall survival, adverse events (AEs), and projected market shares of various treatments. RESULTS: In a hypothetical commercial health plan of 30,000,000 members, 884 patients were estimated to be eligible for 2L treatment over a three-year time period. Without avelumab, the total cost for treating patients with mUC was estimated to be US$70,268,035. The introduction of avelumab increased total costs by $73,438 (0.10% increase). In a hypothetical Medicare health plan of 30,000,000 beneficiaries, a total of 4,705 patients were estimated to be eligible for 2L treatment. Without avelumab, the total cost for treating patients with mUC was estimated to be $292,923,098 from a Medicare perspective; however, with avelumab, there was an increase of $719,324 (0.25% increase) in total costs. Results of the sensitivity analyses demonstrated a cost-neutral impact across all tested scenarios from both perspectives. CONCLUSION: The BIM estimated that avelumab would have a cost-neutral impact within a US commercial and a Medicare health plan. Overall, avelumab can be an affordable and valuable treatment option for patients with locally advanced or mUC in the 2L setting. These findings demonstrate a consistently favorable budget impact in both populations. Further studies should be conducted to more comprehensively assess the clinical and economic implications of adding avelumab to the treatment armamentarium of 2L mUC.

Value assessment of immuno-oncology in the treatment of rare tumors in the era of accelerated conditional approvals.

Aim: To conduct a value assessment of an immuno-oncology (IO) therapy for a rare cancer and evaluate whether existing frameworks consider challenges associated with valuing IOs for rare cancers. Materials & methods: Value frameworks developed by American Society of Clinical Oncologists, Memorial Sloan Kettering Cancer Center and National Comprehensive Cancer Network were used to estimate the value of an IO therapy in a rare cancer based on single-arm trial data and retrospective studies. Results: Paucity of direct evidence comparing rare cancer treatments and lack of acceptance of indirect comparisons hinder appropriate value assessment. Measurement of value based on short-term outcomes may not capture the value of IOs, where survival is often characterized by a plateau. Conclusion: Further work is required to factor in nuances associated with rare cancers and guide end users of the frameworks. To capture true value, multiple or more holistic value assessments are required.

Assessment-Schedule Matching in Unanchored Indirect Treatment Comparisons of Progression-Free Survival in Cancer Studies.

BACKGROUND: The timing of efficacy-related clinical events recorded at scheduled study visits in clinical trials are interval censored, with the interval duration pre-determined by the study protocol. Events may happen any time during that interval but can only be detected during a planned or unplanned visit. Disease progression in oncology is a notable example where the time to an event is affected by the schedule of visits within a study. This can become a source of bias when studies with varying assessment schedules are used in unanchored comparisons using methods such as matching-adjusted indirect comparisons. OBJECTIVE: We illustrate assessment-time bias (ATB) in a simulation study based on data from a recent study in second-line treatment for locally advanced or metastatic urothelial carcinoma, and present a method to adjust for differences in assessment schedule when comparing progression-free survival (PFS) against a competing treatment. METHODS: A multi-state model for death and progression was used to generate simulated death and progression times, from which PFS times were derived. PFS data were also generated for a hypothetical comparator treatment by applying a constant hazard ratio (HR) to the baseline treatment. Simulated PFS times for the two treatments were then aligned to different assessment schedules so that progression events were only observed at set visit times, and the data were analysed to assess the bias and standard error of estimates of HRs between two treatments with and without assessment-schedule matching (ASM). RESULTS: ATB is highly affected by the rate of the event at the first assessment time; in our examples, the bias ranged from 3 to 11% as the event rate increased. The proposed method relies on individual-level data from a study and attempts to adjust the timing of progression events to the comparator's schedule by shifting them forward or backward without altering the patients' actual follow-up time. The method removed the bias almost completely in all scenarios without affecting the precision of estimates of comparative effectiveness. CONCLUSIONS: Considering the increasing use of unanchored comparative analyses for novel cancer treatments based on single-arm studies, the proposed method offers a relatively simple means of improving the accuracy of relative benefits of treatments on progression times.

Budget impact model of avelumab in patients with metastatic merkel cell carcinoma in the US.

Objective: To estimate the budget impact of avelumab as a treatment option for patients with treatment-naïve first-line (1L) and previously treated second-line or later (2L+) metastatic Merkel cell carcinoma (mMCC) in the US. Methods: A budget impact model was developed to evaluate the addition of avelumab for the treatment of mMCC patients using a hypothetical 30 million-member US health plan over a 3-year time horizon (2019-2021). The comparator treatments included in the analysis were pembrolizumab and nivolumab (other immuno-oncology agents); and the chemotherapies routinely used in the eligible mMCC population. Model inputs included market share uptake of avelumab and other comparators, duration of treatments, and costs (drugs, health care resource utilization, adverse events). The model was evaluated from a commercial payer perspective. Sensitivity analyses were conducted to test uncertainties arising from the input values used in the model. Results: In a hypothetical commercial health plan of 30 million members, 285 patients with mMCC were identified over 3 years; 43 patients received avelumab as a 1L treatment over 3 years. In a world without avelumab, the total health care costs of treating patients with mMCC over 3 years were estimated to be US$11,710,115 from a commercial health plan perspective. With avelumab, there were estimated savings of $2,643,173 considering the total costs related to the treatment of mMCC over 3 years (23% reduction in the budget). The incremental cost per member per month over 3 years was -$0.0025. Conclusion: The model results indicate that the adoption of avelumab as a treatment option for mMCC would likely result in minimal budget impact from a US health plan perspective. Patients with mMCC, a rare condition with a poor prognosis and high unmet need, may benefit greatly from recently approved immunotherapies.

Treatment Patterns, Overall Survival, and Total Healthcare Costs of Advanced Merkel Cell Carcinoma in the USA.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive type of cancer with poor outcomes. OBJECTIVE: To describe treatment patterns, overall survival, and healthcare costs associated with advanced MCC (aMCC) using data from Medicare enrollees who received an aMCC diagnosis in the USA States between 2006 and 2013. METHODS: Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2006 to 2013 were used to describe treatment patterns, 1- and 5-year overall survival, and total healthcare costs for the periods 12 months before aMCC diagnosis and 4-12 months afterward in patients aged ≥ 65 years. RESULTS: We identified 257 patients with an aMCC diagnosis, of whom 51% had stage IIIb disease and 49% had stage IV. Within 4 months after diagnosis, 84% of patients (n = 216) received treatment; 45% (n = 115) received surgery, 48% (n = 124) radiation therapy, and 31% (n = 80) chemotherapy. Second-line chemotherapy was administered in 33% of patients (n = 26) receiving first-line chemotherapy. Median overall survival was 27 months in patients whose aMCC was diagnosed at stage IIIb and 12 months in patients whose aMCC was diagnosed at stage IV. Median total 12-month direct healthcare costs were US$48,006 (25th-75th percentile range = US$30,594-US$69,797) per patient. Total costs were highest in patients receiving chemotherapy, either alone or combined with radiation and/or surgery (US$52,854; 25th-75th percentile range = US$34,473-US$71,987). CONCLUSION: Most patients with aMCC received initial treatment, including surgery, radiation, and/or chemotherapy, and approximately one-third of those receiving chemotherapy received second-line chemotherapy. Total 12-month direct healthcare costs were highest in patients who received chemotherapy alone or combined with radiation and/or surgery. These poor survival results and high treatment costs highlight the need for effective new aMCC therapies.

Travel burden associated with rare cancers: The example of Merkel cell carcinoma.

BACKGROUND: There are limited data on the travel burden for cancer patients with rare tumor types, such as Merkel cell carcinoma (MCC). OBJECTIVE: The objective of this study was to understand the travel burden of MCC patients. METHODS: This study used data from an MCC registry at the Seattle Cancer Care Alliance (SCCA). All MCC patients enrolled at SCCA with a valid 3-digit ZIP code were included. Patients were followed up from January 1, 2012 until their last follow-up, death, or end of data (January 1, 2017). Travel burden was measured by one-way travel distance to SCCA from each patient's 3-digit ZIP code. Patient demographics, tumor characteristics, and follow-up visit were evaluated and stratified by one-way driving distance of ≤300 and >300 miles. RESULTS: A total of 391 MCC patients were included (68% men, mean age = 67 years [±SD = ±11 years], 67% residing in the West, and 70% white). At diagnosis, 53% of the patients had Stage III or IV MCC. Mean one-way distance traveled by patients was 1,137 (median: 813) miles, and 57% of patients traveled >300 miles. Compared to patients who traveled ≤300 miles, those who traveled >300 miles were more likely to be <70 years old (46% vs 65%; P < 0.001), were diagnosed with advanced stage (III or IV) MCC (46% vs 59%; P = 0.01), had shorter follow-up in the cancer registry (mean: 509 vs 212 days; P < 0.001), and had fewer visits during follow-up (mean: 5.2 vs 2.5; P < 0.001). CONCLUSIONS: In this single cancer center study, the majority of MCC patients trav-eled long distances to receive expert care. Longer travel distances appeared to be associated with younger age, a more advanced stage of cancer at study entry and fewer in-clinic visits, suggesting that travel burden may impact timely and adequate patient care for this rare cancer.

Cost-effectiveness Analysis of Apixaban against Warfarin for Stroke Prevention in Patients with Nonvalvular Atrial Fibrillation in Japan.

PURPOSE: The aim of this study was to evaluate the cost-effectiveness of apixaban compared with to warfarin, current standard of care, for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in Japan. METHODS: A previously published lifetime Markov model was adapted to evaluate the cost-effectiveness of apixaban compared with warfarin in patients with NVAF in Japan. In the same model, the costs associated with each clinical event and background mortality were replaced with Japanese data. Whenever available, some of the utility parameters were derived from Japanese published literature. Lifetime horizon was selected to evaluate the value of the treatment benefit (stroke prevention) against potential risks (such as major bleedings) among patients with NVAF. Direct medical cost, long-term care cost, and quality-adjusted life years (QALYs) were calculated from the payers' perspective. FINDINGS: Compared with warfarin, treatment with apixaban was estimated to increase life expectancy by 0.231 year or 0.240 QALYs while treatment cost increased by ¥511,692 (US $5117 at an exchange rate of US $1 = ¥100). The incremental cost-effectiveness ratio was ¥2,135,743 per QALY (US $21,357 per QALY). On the basis of the results of the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set at approximately ≥¥2,250,000 (US $22,500) per QALY, the probability of apixaban being cost-effective was ≥50%. Assuming a willingness-to-pay threshold of ¥5,000,000 (US $50,000) and ¥6,700,000 (US $67,000) in Japan, the probability of apixaban being cost-effective was 85% and 91%, respectively. CONCLUSION: Although most participants in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial used for the efficacy data of apixaban in the model were non-Japanese patients, the impact of the limitations on our results was considered small, and our results were deemed robust because of the additional effect in Japanese patients compared with that in the global population according to the subanalysis of Japanese patients in the trial. Therefore, based on an adaptation of a published Markov model, apixaban is a cost-effective alternative to warfarin in Japan for stroke prevention among patients with NVAF.

Cost-effectiveness of Apixaban Compared With Edoxaban for Stroke Prevention in Nonvalvular Atrial Fibrillation.

PURPOSE: The purpose of this analysis was to assess the cost-effectiveness of apixaban 5 mg BID versus high- and low-dose edoxaban (60 mg and 30 mg once daily) as intended starting dose strategies for stroke prevention in patients from a UK National Health Service perspective. METHODS: A previously developed and validated Markov model was adapted to evaluate the lifetime clinical and economic impact of apixaban 5 mg BID versus edoxaban (high and low dose) in patients with nonvalvular atrial fibrillation. A pairwise indirect treatment comparison was conducted for clinical end points, and price parity was assumed between apixaban and edoxaban. Costs in 2012 British pounds, life-years, and quality-adjusted life-years (QALYs) gained, discounted at 3.5% per annum, were estimated. FINDINGS: Apixaban was predicted to increase life expectancy and QALYs versus low- and high-dose edoxaban. These gains were achieved at cost-savings versus low-dose edoxaban, thus being dominant and nominal increases in costs versus high-dose edoxaban. The incremental cost-effectiveness ratio of apixaban versus high-dose edoxaban was £6763 per QALY gained. IMPLICATIONS: Apixaban was deemed to be dominant (less costly and more effective) versus low-dose edoxaban and a cost-effective alternative to high-dose edoxaban.

Clinical and Economic Implications of Apixaban Versus Aspirin in the Low-Risk Nonvalvular Atrial Fibrillation Patients.

BACKGROUND AND PURPOSE: Although recommended by guidelines, the benefits of treating patients with atrial fibrillation with a low-stroke risk score, with aspirin or anticoagulants, have not been clearly established. With advent of safer non-vitamin K antagonist oral anticoagulant, we assessed the clinical and economic implications of 5 mg BID of apixaban versus aspirin among patients with a relative low risk of stroke as assessed using the CHADS2 (congestive heart failure, hypertension, age>75, diabetes mellitus, stroke/transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke/transient ischemic attack, vascular disease) stroke risk classification. METHODS: A previously developed and validated Markov model was adapted. A secondary analysis of the Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) study was conducted to estimate event rates in different low-risk cohorts by treatment. Three cohorts (n=1000) with a CHADS2 score of 1, CHA2DS2-VASc score of 1, and CHA2DS2-VASc of score 2 to 4 were simulated to assess the number of clinical events avoided in terms of strokes and major bleeds, as well as life years gained, quality-adjusted life years gained, costs, and incremental costs per quality-adjusted life year gained. RESULTS: Apixaban was associated with fewer strokes and systemic embolism versus aspirin across all subgroups; however, it caused more major bleeding events. The reduction in systemic embolism offset the increase in major bleeding events leading to increased life expectancy and quality-adjusted life year gains, achieved at an increased cost that was lower than the UK threshold of $44,400 (ie, £30,000) per quality-adjusted life year gained across the 3 cohorts examined. CONCLUSIONS: Anticoagulant treatment with apixaban versus aspirin in low-risk patients, as identified using CHADS2 or CHA2DS2-VASc, is projected to increase life expectancy and provide clinical benefits that are cost effective.

Cost-effectiveness of apixaban vs. current standard of care for stroke prevention in patients with atrial fibrillation.

AIMS: Warfarin, a vitamin K antagonist (VKA), has been the standard of care for stroke prevention in patients with atrial fibrillation (AF). Aspirin is recommended for low-risk patients and those unsuitable for warfarin. Apixaban is an oral anticoagulant that has demonstrated better efficacy than warfarin and aspirin in the ARISTOTLE and AVERROES studies, respectively, and causes less bleeding than warfarin. We evaluated the potential cost-effectiveness of apixaban against warfarin and aspirin from the perspective of the UK payer perspective. RESULTS AND METHODS: A lifetime Markov model was developed to evaluate the pharmacoeconomic impact of apixaban compared with warfarin and aspirin in VKA suitable and VKA unsuitable patients, respectively. Clinical events considered in the model include ischaemic stroke, haemorrhagic stroke, intracranial haemorrhage, other major bleed, clinically relevant non-major bleed, myocardial infarction, cardiovascular hospitalization and treatment discontinuations; data from the ARISTOTLE and AVERROES trials and published mortality rates and event-related utility rates were used in the model. Apixaban was projected to increase life expectancy and quality-adjusted life years (QALYs) compared with warfarin and aspirin. These gains were expected to be achieved at a drug acquisition-related cost increase over lifetime. The estimated incremental cost-effectiveness ratio was £11 909 and £7196 per QALY gained with apixaban compared with warfarin and aspirin, respectively. Sensitivity analyses indicated that results were robust to a wide range of inputs. CONCLUSIONS: Based on randomized trial data, apixaban is a cost-effective alternative to warfarin and aspirin, in VKA suitable and VKA unsuitable patients with AF, respectively.

Cost-effectiveness of apixaban versus other new oral anticoagulants for stroke prevention in atrial fibrillation.

BACKGROUND: Apixaban (5 mg BID), dabigatran (available as 150 mg and 110 mg BID in Europe), and rivaroxaban (20 mg once daily) are 3 novel oral anticoagulants (NOACs) currently approved for stroke prevention in patients with atrial fibrillation (AF). OBJECTIVE: The objective of this study was to evaluate the cost-effectiveness of apixaban against other NOACs from the perspective of the United Kingdom National Health Services. METHODS: A Markov model was developed to evaluate the pharmacoeconomic impact of apixaban versus other NOACs over a lifetime. Pair-wise indirect treatment comparisons were conducted against other NOACs by using ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation), RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy), and ROCKET-AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial results for the following end points: ischemic stroke, hemorrhagic stroke, intracranial hemorrhage, other major bleeds, clinically relevant nonmajor bleeds, myocardial infarction, and treatment discontinuations. Outcomes were life-years, quality-adjusted life years gained, direct health care costs, and incremental cost-effectiveness ratios. RESULTS: Apixaban was projected to increase life expectancy versus other NOACs, including dabigatran (both doses) and rivaroxaban. A small increase in therapeutic management costs was observed with apixaban due to projected gains in life expectancy and lower discontinuation rates anticipated on apixaban versus other NOACs through lifetime. The estimated incremental cost-effectiveness ratio was £9611, £4497, and £5305 per quality-adjusted life-year gained with apixaban compared with dabigatran 150 mg BID, dabigatran 110 mg BID, and rivaroxaban 20 mg once daily, respectively. Sensitivity analyses indicated that results were robust over a wide range of inputs. CONCLUSIONS: Although our analysis was limited by the absence of head-to-head trials, based on the indirect comparison data available, our model projects that apixaban may be a cost-effective alternative to dabigatran 150 mg BID, dabigatran 110 mg BID, and rivaroxaban 20 mg once daily for stroke prevention in AF patients from the perspective of the United Kingdom National Health Services.

Cost of venous thromboembolism in hospitalized medically ill patients.

PURPOSE: The results of a study to estimate the economic costs of venous thromboembolism (VTE) in hospitalized nonsurgical patients during initial admissions and subsequent to hospital discharge are presented. METHODS: Using a database linking admission records from more than 150 U.S. hospitals to health insurance claims, 49,948 patients 40 years of age or older who were hospitalized at least once during a 6-year period for diagnoses other than VTE or traumatic injury and who met other inclusion criteria were identified. Costs were tallied from the index admission to postdischarge day 180 for patients with and patients without evidence of VTE. Ordinary least-squares regression was used to estimate the independent relationship between VTE and total health care costs, controlling for differences in patient characteristics. RESULTS: Two hundred forty-two patients (0.5%) had VTE during the index admission, 317 (0.6%) had VTE after the index admission discharge; in total, 559 (1.1%) had VTE through postdischarge day 180. Among the 242 patients with VTE during their index admission, the adjusted mean total health care costs over 180 days were $17,848 higher than among those without VTE ($47,416 versus $29,568, p < 0.001); for the 317 patients with postdischarge VTE, the adjusted mean total 180-day costs were $51,863 higher than for those without postdischarge VTE ($74,136 versus $22,273, p < 0.001). CONCLUSION: Among medically ill patients admitted to the hospital, health care costs were significantly higher among those who developed VTE during hospitalization or after discharge compared with those who did not develop VTE.

Prevalence of high-risk cardiovascular conditions and the status of hypertension management among hypertensive adults 65 years and older in the United States: analysis of a primary care electronic medical records database.

This study compared the prevalence of high-risk cardiovascular (CV) conditions, antihypertensive medication treatment patterns, and demographic and clinical characteristics associated with blood pressure (BP) goal attainment between elderly (65 years and older) and nonelderly (younger than 65 years) adults with hypertension. Retrospective cohort study was conducted using an electronic medical record database among patients receiving at least 1 antihypertensive medication. CV risk profiles were assessed by International Classification of Diseases, 9th Revision diagnosis codes. Treatment patterns were assessed by the number of antihypertensive medications prescribed. BP goal attainment was determined by the mean of the last 2 BP readings during 1 year of follow-up. Logistic regression estimated the odds of achieving BP goal. There were 61,355 nonelderly (mean age, 51.8 years) and 47,796 elderly (mean age, 73.2 years) patients in the study. Elderly patients had statistically significant higher levels of isolated systolic hypertension and complicated hypertension. Elderly patients had statistically significant higher levels of prescribing patterns characterized by multiple antihypertensive medications but statistically significant lower levels of BP goal attainment. Age 65 years and older, African American race, body mass index ≥30, and the presence of complicated hypertension were found to be statistically significant factors contributing to a lower likelihood of BP goal attainment. Despite aggressive antihypertensive treatment, elderly patients are less likely to achieve BP goals.

Impact of worsening renal function during hospital admission on resource utilization in patients with heart failure.

Renal impairment frequently accompanies heart failure (HF) and is a recognized independent risk factor for morbidity and mortality. Few data are available assessing the impact of worsening renal function (WRF) during hospitalization on health care resource use in patients with HF. Health Insurance Portability and Accountability Act-compliant, de-identified, clinical, laboratory, and economic data for patients admitted to a tertiary care medical center with a primary diagnosis of HF were extracted by MedMining and reviewed retrospectively by the authors. Patients were excluded if they had no previous HF or were admitted for acute coronary syndrome or coronary artery bypass grafting within 30 days of index hospitalization. WRF was defined as ≥ 0.3 mg/dl increase in serum creatinine from baseline at any time during hospitalization. Of 5,803 hospitalized patients with primary HF diagnosis, 827 patients (14%) fulfilled all prespecified inclusion and exclusion criteria (74 ± 14 years of age, 43% men, 98% white, admission serum creatinine 1.4 ± 0.9 mg/dl, estimated glomerular filtration rate < 90 ml/min/1.73 m(2) at admission in 83%). During index hospitalization, WRF was identified in nearly 33%. Compared to patients without WRF, those with WRF had greater prevalence of diabetes (54% vs 43%), lower estimated glomerular filtration rate (44 ± 30 vs 62 ± 35 ml/min/1.73 m(2)), higher serum potassium (4.3 ± 0.7 vs 4.2 ± 0.7 mEq/L), and higher B-type natriuretic peptide (845 ± 821 vs 795 ± 947 pg/ml) at baseline (all p values < 0.05). Patients developing WRF incurred higher total inpatient costs ($10,977, range 671 to 212,819, vs $7,820, range 697 to 269,797, p < 0.001) and longer hospital stay (8.2 ± 6.8 vs 5.7 ± 5.5 days, p < 0.001). In conclusion, occurrence of WRF during HF-related hospitalization is associated with higher hospitalization costs and longer hospital stay.

Associations between worsening renal function and 30-day outcomes among Medicare beneficiaries hospitalized with heart failure.

BACKGROUND: Kidney disease is common among patients with heart failure, but relationships between worsening renal function (WRF) and outcomes after hospitalization for heart failure are poorly understood, especially among patients with preserved systolic function. We examined associations between WRF and 30-day readmission, mortality, and costs among Medicare beneficiaries hospitalized with heart failure. METHODS: We linked data from a clinical heart failure registry to Medicare inpatient claims for patients >or=65 years old hospitalized with heart failure. We defined WRF as a change in serum creatinine >or=0.3 mg/dL from admission to discharge. Main outcome measures were readmission and mortality at 30 days after hospitalization and total inpatient costs. RESULTS: Among 20,063 patients hospitalized with heart failure, WRF was common (17.8%) and more likely among patients with higher baseline comorbidity and more impaired renal function. In unadjusted analyses, WRF was associated with similar subsequent mean inpatient costs (USD 3,255 vs USD 3,277, P = .2) but higher readmission (21.8% vs 20.6%, P = .01) and mortality (10.0% vs 7.2%, P < .001). The differences persisted after adjustment for baseline patient and hospital characteristics (hazard of readmission 1.10 [95% CI 1.02-1.18], hazard of mortality 1.53 [95% CI 1.34-1.75]). Associations of WRF with readmission and mortality were similar between patients with reduced and preserved systolic function. CONCLUSIONS: Worsening renal function during hospitalization for heart failure is an independent predictor of early readmission and mortality in patients with reduced and preserved systolic function.