Risks and cost burden of venous thromboembolism and bleeding for patients undergoing total hip or knee replacement in a managed-care population

Abstract

Background:

Total hip and total knee replacement (THR/TKR) patients are at increased risk of developing venous thromboembolism (VTE). VTE prevention using anticoagulation therapy increases the risk of bleeding. Therefore, any assessment of the cost of VTE and its prevention should also take into consideration risks and costs of bleeding.

Objective:

To assess the risks of developing VTE and bleeding in patients after THR or TKR given real-world use of thromboprophylaxis, and to quantify the incremental cost associated with each.

Methods:

Analyses of insurance healthcare claims from the Ingenix IMPACT National Managed Care Database^TM from January 2004 to December 2008 were conducted. Subjects were ≥18 years and had ≥1 procedure code for THR or TKR. Patients had to have ≥180 days of observation prior to surgery and were observed for ≤3 months after THR or TKR. VTE was defined as ≥1 diagnosis code for deep vein thrombosis or pulmonary embolism. Bleeding events were classified as major or non-major. Risks of VTE or bleeding events were calculated as number of patients with an event divided by number of patients with the procedure. Incremental all-cause healthcare costs associated with VTE or bleeding were calculated as the difference between cohorts of patients without VTE or bleeding matched 1:1 to patients with VTE or bleeding.

Results:

Of 119,729 patients (43,670 THR and 76,059 TKR), 7974 had a VTE event and 4849 had a bleeding event (2216 major bleeding [a subset of ‘any bleeding’]). The risks of VTE, any bleeding, and major bleeding were 6.7, 4.0, and 1.9 events, respectively, per 100 patients. Up to 3 months after THR/TKR, mean incremental all-cause healthcare costs per patient per month associated with VTE, bleeding, and major bleeding were $2729, $2696, and $4304, respectively. Total monthly costs versus matched controls over 3 months were: VTE: $12,333 vs. $9604; any bleeding: $12,481 vs. $9785; major bleeding: $14,015 vs. $9710; p?<?0.001 for all.

Limitations:

Key limitations included potential inaccuracies or omissions in procedures, diagnoses, or costs of claims data; lack of information on the amount of blood transfused or decreases in the hemoglobin level to evaluate the severity of a bleeding event; and potential biases due to the observational design of the study.

Conclusion:

From the managed-care population perspective, in THR/TKR patients the greater incidence of VTE compared to any bleeding and major bleeding translated into a higher cumulative cost burden.     

Healthcare resource utilization and costs associated with venous thromboembolism recurrence in patients with cancer

Abstract

Objective: Patients with cancer are at high risk for developing primary but also recurrent venous thromboembolism (VTE). This study examined healthcare utilization (HRU) and costs related to VTE recurrence among cancer patients.

Methods: Medical and pharmacy claims from the Humana Database were used to compare HRU (outpatient visits, emergency room visits, hospitalizations, and hospitalization days) and healthcare costs among cancer patients with a single VTE event (between 01/2013 and 06/2015) and those with recurrent VTE during the follow-up period (from initiation of anticoagulant therapy until end of eligibility or data availability). All-cause and VTE-related HRU and costs were evaluated using Poisson regression, and healthcare costs were compared using mean differences reported as per-patient-per-year (PPPY).

Results: Of 2,428 newly diagnosed cancer patients who developed VTE, 413 (17.1%) experienced recurrent VTE during the follow-up period (mean = 9 months). Patients with recurrent VTE had higher all-cause and VTE-related HRU and costs compared to those without recurrence. Patients with recurrent VTE also had over 3.19-times more VTE-related hospitalizations (RR [95% CI]?=?3.19 [2.93–3.47]), and 3.88-times more VTE-related hospitalization days (RR [95% CI]?=?3.88 [3.74–4.02]) than patients without a VTE recurrence. Total VTE-related healthcare costs were $39,641 PPPY among patients with recurrent VTE, $29,142 higher compared to those without recurrence ($10,499 PPPY). This difference was mainly driven by hospitalization costs.

Conclusion: Recurrent VTE among cancer patients is associated with significant HRU and healthcare costs, notably hospitalizations. Strategies to reduce VTE recurrence in patients with cancer can contribute to reducing healthcare cost.     

Healthcare resource utilization and costs associated with venous thromboembolism in cancer patients treated with anticoagulants

Abstract

Objective: The standard of care for cancer-related venous thromboembolism (VTE) has been low molecular weight heparin (LMWH), but oral anticoagulants are also widely prescribed. This study compared VTE-related healthcare resource utilization and costs of cancer patients treated with anticoagulants.

Methods: Claims data from Humana Database (January 1, 2013–May 31, 2015) were analyzed. Based on the first anticoagulant received, patients were classified into LMWH, warfarin, or rivaroxaban cohorts. Characteristics were evaluated during the 6 months pre-index date (i.e. the first VTE); VTE-related resource utilization and costs were evaluated during follow-up. Cohorts were compared using rate ratios, and p-values and 95% confidence intervals were calculated. Healthcare costs were evaluated per-patient-per-year (PPPY) and compared using mean cost differences.

Results: A total of 2,428 patients (LMWH: n?=?660; warfarin: n?=?1,061; rivaroxaban: n?=?707) were included. Compared to patients treated with LMWH, patients treated with rivaroxaban had significantly fewer VTE-related hospitalizations, hospitalization days, and emergency room and outpatient visits, resulting in an increase of $12,000 VTE-related healthcare costs PPPY with LMWH vs rivaroxaban. Patients treated with rivaroxaban had significantly lower VTE-related resource utilization compared to patients treated with warfarin; however, VTE-related costs were similar between cohorts. The higher drug costs ($1,519) were offset by significantly lower outpatient (?$1,039) and hospitalization costs (?$522) in rivaroxaban relative to the warfarin cohort.

Conclusions: Healthcare resource use and costs associated with VTE treatment in cancer patients are highest with LMWH relative to warfarin and rivaroxaban.     

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.     

Cost and outcomes associated with rivaroxaban vs enoxaparin for the prevention of postsurgical venous thromboembolism from a US payer’s perspective

Abstract

Objective:

The objective of this analysis was the evaluation of the outcomes and costs associated with rivaroxaban and enoxaparin for the prevention of postsurgical venous thromboembolism (VTE) in patients undergoing total hip replacement (THR) and total knee replacement (TKR) from the US payer perspective.

Methods:

VTE event rates have been reported in three Phase III clinical trials that compared rivaroxaban and enoxaparin for VTE prevention after orthopedic surgery during the prophylaxis (≤35 days for THR patients and 10–14 days for TKR patients) and post-prophylaxis periods (≤90 days following surgery). These data were used in this decision-analytic model to estimate and compare health outcomes and costs associated with rivaroxaban and enoxaparin. The base-case analysis considered the number and costs of symptomatic VTE events during the prophylaxis period only. A 90-day horizon was considered in the sensitivity analysis.

Results:

Following THR, when extended durations of prophylaxis (35 days) were compared, rivaroxaban was associated with lower costs than enoxaparin, with total saving costs of $695/patient. When an extended duration of rivaroxaban prophylaxis (35 days) was compared with a short duration (10–14 days) of enoxaparin prophylaxis, rivaroxaban was estimated to prevent 9.9 additional symptomatic VTE events per 1000 patients, while saving $244/patient (rate/1000 patients). In the TKR population, short duration of rivaroxaban prophylaxis was estimated to prevent 13.1 additional symptomatic VTE events per 1000 patients. It was also less costly than short duration enoxaparin prophylaxis, with a saving of $411/patient (rate/1000 patients).

Limitations:

Only statistically significant differences were captured in the base-case economic analysis, and, therefore, differences in pulmonary embolism (PE) and bleeding events were not captured.

Conclusions:

In this model, rivaroxaban reduced total treatment payer costs vs enoxaparin for the prevention of VTE in THR or TKR patients.     

Costs of hospital visits among patients with deep vein thrombosis treated with rivaroxaban and LMWH/warfarin

Background:

For many years, the standard of care for patients diagnosed with deep vein thrombosis (DVT) has been low-molecular-weight heparin (LMWH) bridging to an oral Vitamin-K antagonist (VKA). The availability of new non-VKA oral anticoagulants (NOAC) agents as monotherapy may reduce the likelihood of hospitalization for DVT patients.

Objective:

To compare hospital visit costs of DVT patients treated with rivaroxaban and LMWH/warfarin.

Methods:

A retrospective claim analysis was conducted using the MarketScan Hospital Drug Database for care provided between January 2011 and December 2013. Adult patients using rivaroxaban or LMWH/warfarin with a primary diagnosis of DVT during the first day of a hospital visit were identified (i.e., index hospital visit). Based on propensity-score methods, historical LMWH/warfarin patients (i.e., patients who received LMWH/warfarin before the approval of rivaroxaban) were matched 4:1 to rivaroxaban patients. The hospital-visit cost difference between these groups was evaluated for the index hospital visit, as well as for total hospital-visit costs (i.e., including index and subsequent hospital visit costs).

Results:

All rivaroxaban users (n?=?134) in the database were well-matched with four LMWH/warfarin users (n?=?536). The mean hospital-visit costs were $5257 for the rivaroxaban cohort and $6764 in the matched-cohort of patients using LMWH/warfarin. The $1508 cost difference was statistically significant between cohorts (95% CI?=?[?$2296; ?$580]; p-value?=?0.002). Total hospital-visit costs were lower for rivaroxaban compared to LMWH/warfarin users within 1, 2, 3, and 6 months after index visit (significantly lower within 1 and 3 months, p-values <0.05)

Limitations:

Limitations were inherent to administrative-claims data, completeness of baseline characteristics, adjustments restricted to observational factors, and lastly the sample size of the rivaroxaban cohort.

Conclusion:

The availability of rivaroxaban significantly reduced the costs of hospital visits in patients with DVT treated with rivaroxaban compared to LMWH/warfarin.     

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.     

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

Objective:

Venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [(PE]) represents a substantial economic burden to the healthcare system. Using data from the randomized EINSTEIN DVT and PE trials, this North American sub-group analysis investigated the potential of rivaroxaban to reduce the length of initial hospitalization in patients with acute symptomatic DVT or PE.

Methods:

A post-hoc analysis of hospitalization and length-of-stay (LOS) data was conducted in the North American sub-set of patients from the randomized, open-label EINSTEIN trial program. Patients received either rivaroxaban (15?mg twice daily for 3 weeks followed by 20?mg once daily; n?=?405) or dose-adjusted subcutaneous enoxaparin overlapping with (guideline-recommended ‘bridging’ therapy) and followed by a vitamin K antagonist (VKA) (international normalized ratio?=?2.0–3.0; n?=?401). The open-label study design allowed for the comparison of LOS between treatment arms under conditions reflecting normal clinical practice. LOS was evaluated using investigator records of dates of admission and discharge. Analyses were carried out in the intention-to-treat population using parametric tests. Costs were applied to the LOS based on weighted mean cost per day for DVT and PE diagnoses obtained from the Healthcare Cost and Utilization Project dataset.

Results:

Of 382 patients hospitalized, 321 (84%), had acute symptomatic PE; few DVT patients required hospitalization. Similar rates of VTE patients were hospitalized in the rivaroxaban and enoxaparin/VKA treatment groups, 189/405 (47%) and 193/401 (48%), respectively. In hospitalized VTE patients, rivaroxaban treatment produced a 1.6-day mean reduction in LOS (median?=?1 day) compared with enoxaparin/VKA (mean?=?4.5 vs 6.1; median?=?3 vs 4), translating to total costs that were $3419 lower in rivaroxaban-treated patients.

Conclusion:

In hospitalized North American patients with VTE, treatment with rivaroxaban produced a statistically significant reduction in LOS. When treating DVT and PE patients, clinicians should consider newer anti-coagulants with less complex treatment regimens.     

Cost-effectiveness of rivaroxaban compared with enoxaparin plus a vitamin K antagonist for the treatment of venous thromboembolism

Background:

Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is commonly treated with a low-molecular-weight heparin such as enoxaparin plus a vitamin K antagonist (VKA) to prevent recurrence. Administration of enoxaparin?+?VKA is hampered by complexities of laboratory monitoring and frequent dose adjustments. Rivaroxaban, an orally administered anticoagulant, has been compared with enoxaparin?+?VKA in the EINSTEIN trials. The objective was to evaluate the cost-effectiveness of rivaroxaban compared with enoxaparin?+?VKA as anticoagulation treatment for acute, symptomatic, objectively-confirmed DVT or PE.

Methods:

A Markov model was built to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios associated with rivaroxaban compared to enoxaparin?+?VKA in adult patients treated for acute DVT or PE. All patients entered the model in the ‘on-treatment’ state upon commencement of oral rivaroxaban or enoxaparin?+?VKA for 3, 6, or 12 months. Transition probabilities were obtained from the EINSTEIN trials during treatment and published literature after treatment. A 3-month cycle length, US payer perspective ($2012), 5-year time horizon and a 3% annual discount rate were used.

Results:

Treatment with rivaroxaban cost $2,448 per-patient less and was associated with 0.0058 more QALYs compared with enoxaparin?+?VKA, making it a dominant economic strategy. Upon one-way sensitivity analysis, the model’s results were sensitive to the reduction in index VTE hospitalization length-of-stay associated with rivaroxaban compared with enoxaparin?+?VKA. At a willingness-to-pay threshold of $50,000/QALY, probabilistic sensitivity analysis showed rivaroxaban to be cost-effective compared with enoxaparin?+?VKA approximately 76% of the time.

Limitations:

The model did not account for the benefits associated with an oral and minimally invasive administration of rivaroxaban. ‘Real-world’ applicability is limited because data from the EINSTEIN trials were used in the model. Also, resource utilization and costs were based on the US healthcare system.

Conclusion:

Rivaroxaban is a cost-effective option for anticoagulation treatment of acute VTE patients.     

In-hospital risk of venous thromboembolism and bleeding and associated costs for patients undergoing total hip or knee arthroplasty

Abstract

Objective:

Benefits of anti-coagulation for venous thromboembolism (VTE) prevention in total hip and knee arthroplasty (THA/TKA) may be offset by increased risk of bleeding. The aim was to assess in-hospital risk of VTE and bleeding after THA/TKA and quantify any increased costs.

Methods:

Healthcare claims from the Premier Perspective^TM Comparative Hospital Database (January 2000–September 2008) were selected for subjects ≥18 years with ≥1 diagnosis code for THA/TKA. VTE was defined as ≥1 code for deep vein thrombosis or pulmonary embolism. Bleeding was classified as major/non-major. Incremental in-hospital costs associated with VTE and bleeding were calculated as cost differences between inpatients with VTE or bleeding matched 1:1 with inpatients without VTE or bleeding.

Results:

A total of 820,197 inpatient stays were identified: 8042 had a VTE event and 7401 a bleeding event (2740 major bleeding). The risks of VTE, any bleeding, and major bleeding were 0.98, 0.90, and 0.33/100 inpatient stays, respectively. Mean incremental in-hospital costs per inpatient were $2663 for VTE, $2028 for bleeding, and $3198 for major bleeding.

Limitations:

These included possible inaccuracies or omissions in procedures, diagnoses, or costs of claims data; no information on the amount of blood transfused or decreases in the hemoglobin level to evaluate bleeding event severity; and potential biases due to the observational design of the study.

Conclusions:

In-hospital risk and incremental all-cause costs with THA/TKA were higher for VTE than for bleeding. Despite higher costs, major bleeding occurred less frequently than VTE, suggesting a favorable benefit/risk profile for VTE prophylaxis in THA/TKA.     

Clinical and economic benefits of extended treatment with apixaban for the treatment and prevention of recurrent venous thromboembolism in Canada

Background and objective Venous thromboembolism (VTE) is associated with long-term clinical and economic burden. Clinical guidelines generally recommend at least 3 months of anticoagulation, but, in clinical practice, concerns over bleeding risk often limit extended treatment. Apixaban was studied for extended VTE treatment in the AMPLIFY-EXT trial, demonstrating superiority to placebo in VTE reduction without increasing risk of major bleeding. This study assessed the long-term clinical and economic benefits of extending treatment with apixaban when clinical equipoise exists compared to standard of care with enoxaparin/warfarin and other novel oral anti-coagulants (NOACs) for the treatment and prevention of recurrent VTE in Canada.

Methods A Markov model was developed to follow patients with VTE over their lifetimes. Efficacy and safety for apixaban and enoxaparin/warfarin were based on AMPLIFY and AMPLIFY-EXT, while relative efficacy to other NOACs was synthesized by network meta-analysis (NMA). Dosages for NOACs and enoxaparin/warfarin were based on their respective trials and were given up to 18 months and up to 6 months, followed by no treatment, respectively. Patient quality adjusted life years (QALYs) were based on published studies, and costs for resource utilization were from a Ministry of Health perspective, expressed as 2014 CAD ($).

Results Extended treatment with apixaban compared to enoxaparin/warfarin resulted in fewer recurrent VTEs, VTE-related deaths, and bleeding events, but at slightly increased cost. The incremental cost-effectiveness ratio was $4828 per QALY gained. Compared to other NOACs, apixaban had the fewest bleeding events, similar recurrent VTE events, and the lowest overall cost, which was driven by the strong bleeding profile. In scenario analyses of acute and lifetime treatments, apixaban was cost-effective against all strategies.

Conclusions Extended treatment with apixaban can offer substantial clinical benefits and is a cost-effective alternative to enoxaparin/warfarin and other NOACs.     

Cost-effectiveness analysis of rivaroxaban for treatment and secondary prevention of venous thromboembolism in the Netherlands

Background: Until recently, standard treatment of venous thromboembolism (VTE) concerned a combination of short-term low-molecular-weight heparin (LMWH) and long-term vitamin-K antagonist (VKA). Risk of bleeding and the requirement for regular anticoagulation monitoring are, however, limiting their use. Rivaroxaban is a novel oral anticoagulant associated with a significantly lower risk of major bleeds (hazard ratio?=?0.54, 95% confidence interval?=?0.37–0.79) compared to LMWH/VKA therapy, and does not require regular anticoagulation monitoring.

Aims: To evaluate the health economic consequences of treating acute VTE patients with rivaroxaban compared to treatment with LMWH/VKA, viewed from the Dutch societal perspective.

Methods: A life-time Markov model was populated with the findings of the EINSTEIN phase III clinical trial to analyze cost-effectiveness of rivaroxaban therapy in treatment and prevention of VTE from a Dutch societal perspective. Primary model outcomes were total and incremental quality-adjusted life years (QALYs), as well as life expectancy and costs.

Results: Over a patient’s lifetime, rivaroxaban was shown to be dominant, with health gains of 0.047 QALYs and cost savings of €304 compared to LMWH/VKA therapy. Dominance was robustly present in all sensitivity analyses. Major drivers of the differences between the two treatment arms were related to anticoagulation monitoring (medical costs, travel costs, and loss of productivity) and the occurrence of major bleeds.

Conclusion: Rivaroxaban treatment of patients with venous thromboembolism results in health gains and cost savings compared to LMWH/VKA therapy. This conclusion holds for the Dutch setting, both for the societal perspective, as well as the healthcare perspective.     

Medical cost reductions associated with the usage of novel oral anticoagulants vs warfarin among atrial fibrillation patients,based on the RE-LY,ROCKET-AF,and ARISTOTLE trials

Abstract

Objective:

The randomized clinical trials, RE-LY, ROCKET-AF, and ARISTOTLE, demonstrate that the novel oral anticoagulants (NOACs) are effective options for stroke prevention among non-valvular atrial fibrillation (AF) patients. This study aimed to evaluate the medical cost reductions associated with the use of individual NOACs instead of warfarin from the US payer perspective.

Methods:

Rates for efficacy and safety clinical events for warfarin were estimated as the weighted averages from the RE-LY, ROCKET-AF and ARISTOTLE trials, and event rates for NOACs were determined by applying trial hazard ratios or relative risk ratios to such weighted averages. Incremental medical costs to a US health payer of an AF patient experiencing a clinical event during 1 year following the event were obtained from published literature and inflation adjusted to 2010 cost levels. Medical costs, excluding drug costs, were evaluated and compared for each NOAC vs warfarin. Sensitivity analyses were conducted to determine the influence of variations in clinical event rates and incremental costs on the medical cost reduction.

Results:

In a patient year, the medical cost reduction associated with NOAC usage instead of warfarin was estimated to be ?$179, ?$89, and ?$485 for dabigatran, rivaroxaban, and apixaban, respectively. When clinical event rates and costs were allowed to vary simultaneously, through a Monte Carlo simulation, the 95% confidence interval of annual medical costs differences ranged between ?$424 and +$71 for dabigatran, ?$301 and +$135 for rivaroxaban, and ?$741 and ?$252 for apixaban, with a negative number indicating a cost reduction. Of the 10,000 Monte-Carlo iterations 92.6%, 79.8%, and 100.0% were associated with a medical cost reduction >$0 for dabigatran, rivaroxaban, and apixaban, respectively.

Conclusions:

Usage of the NOACs, dabigatran, rivaroxaban, and apixaban may be associated with lower medical (excluding drug costs) costs relative to warfarin, with apixaban having the most substantial medical cost reduction.     

Impact of upper and lower gastrointestinal blood loss on healthcare utilization and costs: a systematic review

Abstract

Objectives:

Gastrointestinal (GI) blood loss is a common medical condition which can have serious morbidity and mortality consequences and may pose an enormous burden on healthcare utilization. The purpose of this study was to conduct a systematic review to evaluate the impact of upper and lower GI blood loss on healthcare utilization and costs.

Methods:

We performed a systematic search of peer-reviewed English articles from MEDLINE published between 1990 and 2010. Articles were limited to studies with patients ≥18 years of age, non-pregnant women, and individuals without anemia of chronic disease, renal disease, cancer, congestive heart failure, HIV, iron-deficiency anemia or blood loss due to trauma or surgery. Two reviewers independently assessed abstract and article relevance.

Results:

Eight retrospective articles were included which used medical records or claims data. Studies analyzed resource utilization related to medical care although none of the studies assessed indirect resource use or costs. All but one study limited assessment of healthcare utilization to hospital use. The mean cost/hospital admission for upper GI blood loss was reported to be in the range $3180–8990 in the US, $2500–3000 in Canada and, in the Netherlands, the mean hospital cost/per blood loss event was €11,900 for a bleeding ulcer and €26,000 for a bleeding and perforated ulcer. Mean cost/ hospital admission for lower GI blood loss was $4800 in Canada, and $40,456 for small bowel bleeding in the US.

Conclusions:

Our findings suggest that the impact of GI blood loss on healthcare costs is substantial but studies are limited. Additional investigations are needed which examine both direct and indirect costs as well as healthcare costs by source of GI blood loss focusing on specific populations in order to target treatment pathways for patients with GI blood loss.     

Cost-effectiveness of rivaroxaban in the prevention of venous thromboembolism: A Canadian analysis using the Ontario Ministry of Health Perspective

Abstract

Objectives:

A cost-effectiveness model for rivaroxaban evaluated the cost-effectiveness of prophylaxis with rivaroxaban (a once-daily, orally administered Factor Xa inhibitor) vs enoxaparin in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) and total knee replacement (TKR). This Canadian analysis was conducted using the Ontario Ministry of Health perspective over a 5-year time horizon. The model combined clinical data and builds upon existing economic models.

Methods:

The model included both acute VTE (represented as a decision tree) and long-term complications (represented as a Markov process with 1-year cycles) phases. The model allowed VTE event rates, quality-adjusted life expectancy and direct medical costs to be estimated over a 5-year time horizon, based on current approved practice patterns in Canada. A number of one-way sensitivity analyses were performed on the baseline assumptions, including a comparison of rivaroxaban with dalteparin, and probabilistic sensitivity analyses were performed to address any uncertainty concerning model inputs.

Results:

When comparing equal durations of therapy, rivaroxaban dominated enoxaparin in the prevention of VTE events in patients undergoing THR and TKR, providing more benefit at a lower cost. Rivaroxaban was cost-effective when comparing 35 days’ prophylaxis with 14 days’ prophylaxis with enoxaparin following THR. One-way and probabilistic sensitivity analyses demonstrated that the results of the economic analysis were robust to variations in key inputs. Rivaroxaban remained dominant during one-way sensitivity analyses comparing rivaroxaban with dalteparin after THR or TKR.

Limitations:

Although clinical trial data were used in the prophylaxis module, assumptions and values used in the post-prophylaxis and long-term complication (LTC) modules were based on several different literature sources; it was not always possible to source Canadian data.

Conclusions:

This economic analysis suggests that the use of rivaroxaban for the prophylaxis of VTE after THR or TKR in Canada was cost-effective.     

Economic burden of venous thromboembolism: a systematic review

Abstract

Objective:

Deep vein thrombosis and pulmonary embolism – together referred to as venous thromboembolism (VTE) – result in a major burden on healthcare systems. However, to the authors’ knowledge no comprehensive review of the economic burden of VTE has so far been published.

Methods:

A literature search was carried out to identify references published in English since 1997 using Medline, the Cochrane Library and the Health Economic Evaluations Database. The primary outcomes of interest were ‘all-cause’ VTE and VTE after major orthopedic surgery.

Results:

A total of 1,037 full research articles and abstracts were screened for inclusion in the review. Of these, ten cost-of-illness studies were identified that met the inclusion criteria and are included in the current review. The results of large US database analyses vary, indicating costs of the initial VTE of approximately US$3,000–9,500. The total costs related to VTE over 3 months (US$5,000), 6 months (US$10,000) and 1 year (US$33,000) were considerable. Studies conducted in the European Union indicate lower additional inpatient costs after VTE of €1,800 after 3 months and €3,200 after 1 year, which still represent a considerable impact on healthcare systems. Complications after VTE can be very expensive, with estimates of the additional cost of treating the post-thrombotic syndrome ranging from $426 to $11,700 and heparin-induced thrombocytopenia from $3,118 to $41,133. A limitation of studies using older data is that recent changes in the treatment of VTE may affect the generalizability of these findings.

Conclusions:

Complications associated with VTE are frequent and costly. In particular, the cost of complications resulting from prophylaxis and treatment of VTE, such as post-thrombotic syndrome and heparin-induced thrombocytopenia, had a considerable economic impact.     

Cost-effectiveness of rivaroxaban versus apixaban for the initial treatment of venous thromboembolism and extended prevention of recurrences in the UK

Abstract

Aim: To evaluate the relative cost-effectiveness of using rivaroxaban vs apixaban for the initial treatment plus extended prevention of venous thromboembolism (VTE) in the UK. Extended prevention was assessed using a 10-mg rivaroxaban dose, as the 20-mg dose has already been evaluated.

Methods: A Markov model compared the health outcomes and costs of treating VTE patient cohorts with either rivaroxaban (15?mg twice daily for 3 weeks, followed by 20?mg once daily for 6 months, then extended prevention with 10?mg once daily) or apixaban (10?mg twice daily for 1 week, followed by 5?mg twice daily for 6 months, then extended prevention with 2.5?mg twice daily) over a lifetime horizon. The model included an initial acute treatment and prevention phase (0–6?months) and an extended prevention phase (6–18 months). Efficacy and safety data were derived from two network meta-analyses. Reference treatment comparators were derived from the EINSTEIN-Pooled study and EINSTEIN-CHOICE trial. Healthcare costs and utility data were derived from published literature.

Results: The rivaroxaban regimen was associated with increased quality-adjusted life years (QALYs) and slightly lower total costs compared with apixaban over a lifetime horizon. Deterministic and probabilistic sensitivity analyses demonstrated that rivaroxaban remained a cost-effective alternative to apixaban over a wide range of parameters. Incremental cost-effectiveness ratio estimates were below the £20,000 per QALY threshold in 74.1% of 2,000 model simulations. Scenario analyses further supported that rivaroxaban is a cost-effective alternative to apixaban.

Limitations: Clinical and safety inputs were derived from network meta-analysis, which are subject to inherent limitations whereby small differences between study designs may severely impact efficacy and safety outcomes. Furthermore, these inputs were based on data from clinical trials, which may not reflect real-world data.

Conclusions: Rivaroxaban was associated with a slightly lower total cost and increased QALYs compared with apixaban for VTE management in the UK over a lifetime horizon.     

Real-world comparison of all-cause hospitalizations,hospitalizations due to stroke and major bleeding,and costs for non-valvular atrial fibrillation patients prescribed oral anticoagulants in a US health plan

Aims: To compare the risk of all-cause hospitalization and hospitalizations due to stroke/systemic embolism (SE) and major bleeding, as well as associated healthcare costs for non-valvular atrial fibrillation (NVAF) patients initiating apixaban, dabigatran, rivaroxaban, or warfarin.

Materials and methods: NVAF patients initiating apixaban, dabigatran, rivaroxaban, or warfarin were selected from the OptumInsight Research Database from January 1, 2013–September 30, 2015. Propensity score matching (PSM) was performed between apixaban and each oral anticoagulant. Cox models were used to estimate the risk of stroke/SE and major bleeding. Generalized linear and 2-part models were used to compare healthcare costs.

Results: Of the 47,634 eligible patients, 8,328 warfarin-apixaban pairs, 3,557 dabigatran-apixaban pairs, and 8,440 rivaroxaban-apixaban pairs were matched. Compared to apixaban, warfarin patients were associated with a significantly higher risk of all-cause (hazard ratio [HR]?=?1.30; 95% confidence interval [CI]?=?1.21–1.40) as well as stroke/SE-related (HR?=?1.60; 95% CI?=?1.23–2.07) and major bleeding-related (HR?=?1.95; 95% CI?=?1.60–2.39) hospitalization; rivaroxaban patients were associated with a higher risk of all-cause (HR?=?1.15; 95% CI?=?1.07–1.24) and major bleeding-related hospitalization (HR?=?1.71; 95% CI?=?1.39–2.10); and dabigatran patients were associated with a higher risk of major bleeding hospitalization (HR?=?1.46, 95% CI?=?1.02–2.10). Warfarin patients had significantly higher major bleeding-related and total all-cause healthcare costs compared to apixaban patients. Rivaroxaban patients had significantly higher major bleeding-related costs compared to apixaban patients. No significant results were found for the remaining comparisons.

Limitations: No causal relationships can be concluded, and unobserved confounders may exist in this retrospective database analysis.

Conclusions: This study demonstrated a significantly higher risk of hospitalization (all-cause, stroke/SE, and major bleeding) associated with warfarin, a significantly higher risk of major bleeding hospitalization associated with dabigatran or rivaroxaban, and a significantly higher risk of all-cause hospitalization associated with rivaroxaban compared to apixaban. Lower major bleeding-related costs were observed for apixaban patients compared to warfarin and rivaroxaban patients.