Best Practice Approach to Successful Conversion of Fosaprepitant to Aprepitant IV in a Large Multisite Community Oncology Infusion Center: A Retrospective Analysis.

PURPOSE: To evaluate the impact on cost, time, resource use, and clinic workflow of converting the route of drug administration from a neurokinin-1 receptor antagonist (NK-1 RA) 30-min intravenous (IV) infusion to aprepitant IV, and more specifically to IV push, within a multicenter community oncology practice. METHODS: This was a retrospective, multicenter time, motion, and resource/cost evaluation study. Conversion to aprepitant IV was determined by calculating number of doses of aprepitant IV versus fosaprepitant administered in patients receiving moderately or highly emetogenic chemotherapy regimens. Operational advantages (i.e., supply costs, time saved) of switching from fosaprepitant IV infusion to aprepitant administered as a 2-min IV push were assessed. RESULTS: A total of 12,908 doses of aprepitant IV 130 mg were administered at 13 Rocky Mountain Cancer Centers clinics over an 18-month period. Conversion from fosaprepitant to aprepitant IV reached 90% after 9 months of aprepitant IV initiation. Supply costs per administration were reduced ($2.51 to $0.52) when aprepitant was prepared as an IV push versus an NK-1 RA infusion. The overall time savings per administration of aprepitant was reduced by 90% (from 36.5 to 3.5 min, 33 min saved) as an IV push rather than an infusion. Most of the time saved per administration (30 min) pertained to the infusion nurse, and 3 min was saved by the pharmacy technician. CONCLUSION: Successful conversion to aprepitant, and specifically to a 2-min IV push, provides time, cost, and resource savings, improves operational efficiency, and avoids the negative impact of potential future IV fluid shortages.

Chemotherapy-induced nausea and vomiting (CINV) can have a major impact on quality of life for patients receiving chemotherapy. Intravenous (IV) aprepitant is an approved neurokinin-1 receptor antagonist (NK-1 RA) that has been effective and safe when administered as part of a guideline-recommended regimen in patients receiving chemotherapy. In addition to being approved as a 30-min infusion, aprepitant IV is the only NK-1 RA approved for administration as a 2-min injection. These factors contributed to Rocky Mountain Cancer Centers (RMCC), which is a physician-owned community oncology practice, evaluating the impact on cost, time, and resource use of converting from a 30-min infusion of fosaprepitant to aprepitant IV, and more specifically a 2-min injection. Within 9 months of implementing aprepitant IV at RMCC, the percent utilization compared to fosaprepitant reached over 90%, signifying a successful conversion within the practice. Furthermore, a 2-min injection of aprepitant IV resulted in several operational advantages compared to a 30-min infusion. When accounting for all 13 clinics within RMCC, total monthly time savings to the practice would be over 28,000 min, or approximately 60 workdays per month of saved time. This new workflow is more efficient and allows for pharmacy technicians to complete other necessary tasks in the pharmacy such as cleaning, organizing, managing inventory, drug ordering, and charge/documentation corrections. Time saved by the nurses could be used for enhanced patient care, thoroughly reviewing chemotherapy or other orders, and assisting other nurses.

Cost-minimization analysis of GSTP1c.313A>G genotyping for the prevention of cisplatin-induced nausea and vomiting: A Bayesian inference approach.

BACKGROUND: Chemotherapy-induced nausea and vomiting are concerning adverse events resulting from cancer treatment, and current guidelines recommend the use of neurokinin-1-selective antagonists, such as fosaprepitant, in highly emetogenic schemes. However, the implementation of this strategy may be limited by the cost of treatment. GSTP1 c.313A>G genotype was recently described as a predictor of vomiting related to high-dose cisplatin. We hypothesized that the inclusion of routine GSTP1 c.313A>G screening may be promising in financial terms, in contrast to the wide-spread use of fosaprepitant. METHODS: A cost-minimization analysis was planned to compare GSTP1 c.313A>G genotyping versus overall fosaprepitant implementation for patients with head and neck cancer under chemoradiation therapy with high-dose cisplatin. A decision analytic tree was designed, and conditional probabilities were calculated under Markov chain Monte Carlo simulations using the Metropolis-Hastings algorithm. The observed data included patients under treatment without fosaprepitant, while priors were derived from published studies. RESULTS: To introduce screening with real-time polymerase chain reaction, an initial investment of U$ 39,379.97 would be required, with an amortization cost of U$ 7,272.97 per year. The mean cost of standard therapy with fosaprepitant is U$ 243.24 per patient, and although the initial cost of routine genotyping is higher, there is a tendency of progressive minimization at a threshold of 155 patients (Credible interval-CI: 119 to 216), provided more than one sample is incorporated for simultaneous analysis. A resulting reduction of 35.83% (CI: 30.31 to 41.74%) in fosaprepitant expenditures is then expected with the implementation of GSTP1 c.313A>G genotyping. CONCLUSION: GSTP1 c.313A>G genotyping may reduce the use of preventive support for chemotherapy induced nausea and lower the overall cost of treatment. Despite the results of this simulation, randomized, interventional studies are required to control for known and unknown confounders as well as unexpected expenses.

A cost-analysis model for anticoagulant treatment in the hospital setting.

BACKGROUND: Rivaroxaban is the first oral factor Xa inhibitor approved in the US to reduce the risk of stroke and blood clots among people with non-valvular atrial fibrillation, treat deep vein thrombosis (DVT), treat pulmonary embolism (PE), reduce the risk of recurrence of DVT and PE, and prevent DVT and PE after knee or hip replacement surgery. The objective of this study was to evaluate the costs from a hospital perspective of treating patients with rivaroxaban vs other anticoagulant agents across these five populations. METHODS: An economic model was developed using treatment regimens from the ROCKET-AF, EINSTEIN-DVT and PE, and RECORD1-3 randomized clinical trials. The distribution of hospital admissions used in the model across the different populations was derived from the 2010 Healthcare Cost and Utilization Project database. The model compared total costs of anticoagulant treatment, monitoring, inpatient stay, and administration for patients receiving rivaroxaban vs other anticoagulant agents. The length of inpatient stay (LOS) was determined from the literature. RESULTS: Across all populations, rivaroxaban was associated with an overall mean cost savings of $1520 per patient. The largest cost savings associated with rivaroxaban was observed in patients with DVT or PE ($6205 and $2742 per patient, respectively). The main driver of the cost savings resulted from the reduction in LOS associated with rivaroxaban, contributing to ∼90% of the total savings. Furthermore, the overall mean anticoagulant treatment cost was lower for rivaroxaban vs the reference groups. LIMITATIONS: The distribution of patients across indications used in the model may not be generalizable to all hospitals, where practice patterns may vary, and average LOS cost may not reflect the actual reimbursements that hospitals received. CONCLUSION: From a hospital perspective, the use of rivaroxaban may be associated with cost savings when compared to other anticoagulant treatments due to lower drug cost and shorter LOS associated with rivaroxaban.

Economic analysis of aprepitant-containing regimen to prevent chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy in Hong Kong.

AIM: We aim to evaluate the cost effectiveness of aprepitant-containing regimens for the prevention of chemotherapy-induced nausea and vomiting (CINV) among patients receiving high emetogenic chemotherapy (HEC) in Hong Kong. METHODS: Both cost-effectiveness and cost-utility analyses were conducted utilizing a decision-analytic model to measure the economic costs and clinical outcomes associated with the aprepitant-containing regimen versus a standard regimen in the prevention of CINV. Analyses were conducted on the basis of four published double-blind randomized clinical trials involving different usages of serotonin receptor antagonists. RESULTS: The use of aprepitant-containing regimens is associated with an improvement in quality-adjusted life years (QALYs) compared with non-aprepitant regimens. For cisplatin-based chemotherapy, the incremental cost per QALY gained is HKD 239,644 (1 USD approximates HKD 7.8) when ondansetron is administered on day 1 only. The incremental cost per QALY is HKD 440,950 when ondansetron is used on day 1 to 4. For anthracycline and cyclophosphamide chemotherapy, the aprepitant-containing regimen is associated with incremental cost of HKD 195,442 per QALY gained. Similar results were obtained when other 5HT3 receptor antagonists are used. The use of aprepitant was associated with higher cost of drug but lower costs of emesis-related management. With the cost-effectiveness threshold set at the World Health Organization endorsed criteria of three times gross domestic product (GDP) per capita (three times GDP per capita in Hong Kong in 2011 is HKD 798,078), the current analyses showed that the aprepitant-containing regimen was cost-effective. CONCLUSIONS: In patients undergoing HEC, the use of aprepitant as the anti-emetic is cost-effective in Hong Kong.

New anticoagulants as thromboprophylaxis after total hip or knee replacement.

OBJECTIVES: Due to a high risk of thromboembolism in patients undergoing major orthopedic surgery, it has become standard practice to give thromboprophylactic treatment. We assessed the relative efficacy and cost-effectiveness of two new oral anticoagulants, rivaroxaban and dabigatran, relative to subcutaneous enoxaparin for the prevention of thromboembolism after total hip replacement (THR) and total knee replacement surgery (TKR). METHODS: We conducted a systematic review of the literature to assess efficacy and safety, and evaluated quality of documentation using GRADE. Cost-effectiveness was assessed by developing a decision model. The model combined two modules; a decision tree for the short-term prophylaxis and a Markov model for the long-term complications and survival gain. RESULTS: For rivaroxaban compared with enoxaparin, we found statistically significant decreases in deep vein thrombosis, but also a trend toward increased risk of major bleeding. For mortality and pulmonary embolism there were no statistically significant differences between the treatments. We did not find statistically significant differences between dabigatran and enoxaparin for our efficacy and safety outcomes. Assuming a willingness to pay of EUR62,500 per QALY, rivaroxaban following THR had a probability of 38 percent, and enoxaparin following TKR had a probability of 34 percent of being cost-effective. Clinical efficacy had the greatest impact on decision uncertainty. CONCLUSIONS: Dabigatran and rivaroxaban are comparable with enoxaparin following THR and TKR regarding the efficacy and safety outcomes. However, there is great uncertainty regarding which strategy is the most cost-effective. More research on clinical efficacy of rivaroxaban and dabigatran is likely to change our results.

Conventional and new oral anticoagulants in the treatment of chest disease and its complications.

Oral anticoagulants block the coagulation cascade either by an indirect mechanism (e.g., vitamin K antagonists) or by a direct one (e.g., the novel oral anticoagulants). Vitamin K antagonists are widely used as treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation. Although low molecular weight heparin remains the first line in venous thromboembolism prophylaxis, more recently the novel oral anticoagulants such as dabigatran (initial dose of 110 mg within 1-4 h after surgery, followed by the full dose of 220 mg once daily), rivaroxaban (dose of 10 mg once daily, with the first dose administered 6-10 h after the surgery), and apixaban (dose of 2.5 mg twice daily, starting 12-24 h after surgery, but available only in Europe) are approved for prophylaxis in patients undergoing major orthopedic surgery. The period in which thromboembolic risk abates remains uncertain, and trials of extended therapy are still ongoing. After showing at least noninferiority to warfarin in RE-LY, ROCKET-AF, and ARISTOTLE trials, dabigatran (110 or 150 mg twice daily), rivaroxaban (20 or 15 mg once daily), and apixaban (5 mg twice daily), respectively, were approved also for stroke prevention in patients with atrial fibrillation. While awaiting long-term safety data, the choice among all these available therapies should be based on patient preferences, compliance, and ease of administration, as well as on local factors affecting cost-effectiveness.

A multi-perspective cost-effectiveness analysis comparing rivaroxaban with enoxaparin sodium for thromboprophylaxis after total hip and knee replacement in the German healthcare setting.

BACKGROUND: Patients undergoing major orthopaedic surgery (MOS), such as total hip (THR) or total knee replacement (TKR), are at high risk of developing venous thromboembolism (VTE). For thromboembolism prophylaxis, the oral anticoagulant rivaroxaban has recently been included in the German diagnosis related group (DRG) system. However, the cost-effectiveness of rivaroxaban is still unclear from both the German statutory health insurance (SHI) and the German hospital perspective. OBJECTIVES: To assess the cost-effectiveness of rivaroxaban from the German statutory health insurance (SHI) perspective and to analyse financial incentives from the German hospital perspective. METHODS: Based on data from the RECORD trials and German cost data, a decision tree was built. The model was run for two settings (THR and TKR) and two perspectives (SHI and hospital) per setting. RESULTS: Prophylaxis with rivaroxaban reduces VTE events (0.02 events per person treated after TKR; 0.007 after THR) compared with enoxaparin. From the SHI perspective, prophylaxis with rivaroxaban after TKR is cost saving (€27.3 saving per patient treated). However, the cost-effectiveness after THR (€17.8 cost per person) remains unclear because of stochastic uncertainty. From the hospital perspective, for given DRGs, the hospital profit will decrease through the use of rivaroxaban by €20.6 (TKR) and €31.8 (THR) per case respectively. CONCLUSIONS: Based on our findings, including rivaroxaban for reimbursement in the German DRG system seems reasonable. Yet, adequate incentives for German hospitals to use rivaroxaban are still lacking.

Value-of-information analysis to reduce decision uncertainty associated with the choice of thromboprophylaxis after total hip replacement in the Irish healthcare setting.

BACKGROUND: The National Centre for Pharmacoeconomics, in collaboration with the Health Services Executive, considers the cost effectiveness of all new medicines introduced into Ireland. Health Technology Assessments (HTAs) are conducted in accordance with the existing agreed Irish HTA guidelines. These guidelines do not specify a formal analysis of value of information (VOI). OBJECTIVE: The aim of this study was to demonstrate the benefits of using VOI analysis in decreasing decision uncertainty and to examine the viability of applying these techniques as part of the formal HTA process for reimbursement purposes within the Irish healthcare system. METHOD: The evaluation was conducted from the Irish health payer perspective. A lifetime model evaluated the cost effectiveness of rivaroxaban, dabigatran etexilate and enoxaparin sodium for the prophylaxis of venous thromboembolism after total hip replacement. The expected value of perfect information (EVPI) was determined directly from the probabilistic analysis (PSA). Population-level EVPI (PEVPI) was determined by scaling up the EVPI according to the decision incidence. The expected value of perfect parameter information (EVPPI) was calculated for the three model parameter subsets: probabilities, preference weights and direct medical costs. RESULTS: In the base-case analysis, rivaroxaban dominated both dabigatran etexilate and enoxaparin sodium. PSA indicated that rivaroxaban had the highest probability of being the most cost-effective strategy over a threshold range of &U20AC;0-&U20AC;100 000 per QALY. At a threshold of &U20AC;45 000 per QALY, the probability that rivaroxaban was the most cost-effective strategy was 67%. At a threshold of &U20AC;45 000 per QALY, assuming a 10-year decision time horizon, the PEVPI was &U20AC;11.96 million and the direct medical costs subset had the highest EVPPI value (&U20AC;9.00 million at a population level). In order to decrease uncertainty, a more detailed costing study was undertaken. In the subsequent analysis, rivaroxaban continued to dominate both comparators. In the PSA, rivaroxaban continued to have the highest probability of being optimal over the threshold range &U20AC;0-&U20AC;100 000 per QALY. At &U20AC;45 000 per QALY, the probability that rivaroxaban was the most cost-effective strategy increased to 80%. At &U20AC;45 000 per QALY, the 10-year PEVPI decreased to &U20AC;3.58 million and the population value associated with the direct medical costs fell to &U20AC;1.72 million. CONCLUSION: This increase in probability of cost effectiveness, coupled with a substantially reduced potential opportunity loss could influence a decision maker's confidence in making a reimbursement decision. On discussions with the decision maker we now intend to incorporate the use of VOI into our HTA process.

Anticoagulation prophylaxis in orthopedic surgery: an efficiency frontier approach.

UNLABELLED: This study assesses the use of new anticoagulants for the prevention of venous thromboembolism (VTE) in patients undergoing elective orthopedic surgery using traditional cost-effectiveness analysis and efficiency frontier methodology. RATIONALE: Efficiency frontier methodology has the potential to systematically improve the information used in policy and decision making, though it is still relatively uncommon in health economics. Anticoagulation in elective orthopedic surgery provides a fitting and timely case study for examining the influence of choosing one methodology over another. METHODS: An economic model was developed to capture the relative benefits and consequences of choosing one anticoagulation strategy over another in the context of orthopedic surgery. Three novel oral anticoagulants (apixaban, rivaroxaban, dabigatran) are compared with enoxaparin 40 mg daily from the UK National Health Service perspective using traditional cost-effectiveness estimates (cost/quality-adjusted life years, cost/life years gained) and the efficiency frontier. The latter explicitly includes embolic and bleeding events as outcomes. A 5-year time horizon was adopted. RESULTS: Total discounted costs ranged from about £200 000 to £431 000 over 5 years per 1000 patients undergoing elective total hip arthroplasty, and from £243 000 to £463 000 per 1000 patients for elective total knee arthroplasty. Analysis of the efficiency frontier demonstrates that apixaban and rivaroxaban are the preferred choices, depending on the outcome examined and the type of surgery. In terms of safety, apixaban is associated with more bleeding events avoided; yet, rivaroxaban demonstrated better VTE outcomes. CONCLUSION: Traditional cost-effectiveness analysis systematically excludes information related to the safety profiles of these anticoagulants. The efficiency frontier approach presented in this study provides critical information, without substantial effort, to permit a fully informed decision by taking into account all relevant outcomes as they relate to the costs associated with treatment choice.

Cost effectiveness of rivaroxaban versus enoxaparin for prevention of post-surgical venous thromboembolism from a U.S. payer's perspective.

BACKGROUND: Major orthopaedic surgery, such as total hip replacement (THR) and total knee replacement (TKR), is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: Clinical trials have demonstrated the efficacy of rivaroxaban, a once-daily, orally administered Factor Xa inhibitor, for the prevention of VTE in patients undergoing THR or TKR. This analysis evaluated the cost effectiveness of rivaroxaban compared with enoxaparin, from a U.S. payer's perspective. METHODS: A decision-analytic model was developed to compare the costs and outcomes associated with rivaroxaban and enoxaparin for the prevention of VTE. The model replicated short-term clinical outcomes from the phase III RECORD trials. RECORD1 and RECORD2 compared rivaroxaban 10 mg daily (qd), given for 35 days, with enoxaparin 40 mg qd, given for 35 days or 10 to 14 days, respectively, in patients undergoing THR. RECORD3 compared 10 mg of rivaroxaban qd for 10 to 14 days versus 40 mg of enoxaparin qd for 10 to 14 days in patients undergoing TKR. The decision-analytic model also included data on long-term complications and sequelae as captured in observational studies and databases. It also included direct year 2010 medical costs over 1-year and 5-year time horizons. A series of sensitivity analyses were performed to determine the impact of different factors on the results of the model. Results of the cost-effectiveness analysis were reported in terms of symptomatic VTE events avoided. RESULTS: Rivaroxaban was associated with cost savings of $US 511.93 per patient and prevented an average of 0.0145 symptomatic VTE events per patient in the THR population, compared with enoxaparin. For a TKR population, 10 to 14 days of rivaroxaban prophylaxis was associated with cost savings of $US 465.74 and prevented an average 0.0193 symptomatic VTE events per patient. Sensitivity analysis suggested that the results of the model were robust, with cost savings ranging from $US 133.96-629.57 in the THR population and $US 293.01-848.68 in the TKR population, depending on the variables used. Sensitivity analysis also suggested that the economic profile of rivaroxaban is improved when the time horizon of the model is extended from 1 year to 5 years. A probabilistic sensitivity analysis confirmed the findings of baseline results, showing that rivaroxaban was less costly and more effective in all model simulations for both populations. CONCLUSIONS: This decision-analytic model analysis, from the U.S. payer's perspective, concluded that rivaroxaban may be cost saving in both the THR and the TKR populations, when compared with enoxaparin in the U.S.

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

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.

Cost-effectiveness of rivaroxaban versus heparins for prevention of venous thromboembolism after total hip or knee surgery in Sweden.

AIMS: The objective of this study was to evaluate the cost-effectiveness of rivaroxaban versus the low-molecular-weight heparins (LMWH) enoxaparin and dalteparin for the prevention of venous thromboembolism (VTE) after total hip replacement and total knee replacement in Sweden. METHODS: The model included acute venous thromboembolic events and long-term complications over a 5-year time horizon represented by an acute and a chronic phase with 1-year cycles. Transition probabilities were derived from the Regulation of Coagulation in Orthopaedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism (RECORD) clinical trials. RESULTS: In patients undergoing total hip replacement, the incremental cost per additional quality-adjusted life-year of extended prophylaxis for 35 days with rivaroxaban versus 14 days of prophylaxis with enoxaparin or dalteparin was SEK29,400 and SEK35,400, respectively. In total knee replacement patients, 14 days of rivaroxaban dominated 14 days of LMWH as prophylaxis for VTE. CONCLUSION: The results of the economic model consistently showed that, over a 5-year period, rivaroxaban is a cost-effective alternative to 14 days of LMWH for VTE prophylaxis in Sweden.

Economic impact of venous thromboembolism after hip and knee arthroplasty: potential impact of rivaroxaban.

The number of total hip and knee arthroplasties is increasing, with a consequent rise in the number of patients at risk of venous thromboembolism. Each such event is associated with the risk of morbidity and mortality, plus substantial healthcare costs. Consequently, the American College of Chest Physicians guidelines recommend low-molecular-weight heparins, fondaparinux or vitamin K antagonists (usually warfarin) after total hip and knee arthroplasty. However, such agents are also associated with healthcare costs for administration and monitoring. New oral anticoagulants in development may reduce post-arthroplasty symptomatic thromboembolic events and produce potential savings for the healthcare system. This brief article outlines such potential savings with rivaroxaban based on the results of the REgulation of Coagulation in ORthopaedic surgery to prevent Deep vein thrombosis and pulmonary embolism (RECORD) program.

Cost-effectiveness of rivaroxaban after total hip or total knee arthroplasty.

Venous thromboembolism (VTE) following joint replacement surgery represents an economic as well as a clinical burden; however, the risk of thromboembolic events is greatly reduced by appropriate anticoagulation. Rivaroxaban, a Factor Xa inhibitor currently in phase III development, was compared with the low molecular weight heparin enoxaparin in 4 clinical trials, collectively called the RECORD program (REgulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism). In a pooled analysis of data from the RECORD trials, rivaroxaban was superior to enoxaparin regimens in reducing the composite end point of symptomatic venous thromboembolism and all-cause mortality in patients following elective primary total hip or total knee arthroplasty (THA or TKA), with a comparable incidence of major bleeding events. In cost-effectiveness analyses, compared with enoxaparin, rivaroxaban showed the potential to reduce costs associated with the prophylaxis and treatment of thromboembolic events in a post-orthopedic surgery/arthroplasty population.

An indirect comparison, via enoxaparin, of rivaroxaban with dabigatran in the prevention of venous thromboembolism after hip or knee replacement.

OBJECTIVE: To compare the efficacy, in the prevention of venous thromboembolism (VTE), and safety, of rivaroxaban and dabigatran relative to the common comparator enoxaparin. METHODS: Two randomized clinical trials of dabigatran, one after total hip replacement (THR), RE-NOVATE, and one after total knee replacement (TKR), RE-MODEL, were identified as using the same enoxaparin regimen (40 mg once daily given the evening before surgery) and being of comparable duration to two rivaroxaban trials, RECORD1 and RECORD3. Indirect comparisons were performed on both efficacy and safety endpoints. To enable comparisons, symptomatic VTE results were based on the total study duration period, i.e. including the follow-up period. Major bleeding included surgical-site bleeding events. RESULTS: After THR, rivaroxaban 10 mg once daily significantly reduced total VTE and symptomatic VTE relative to dabigatran 220 mg once daily (relative risk 0.34 and 0.19, respectively). After TKR, rivaroxaban significantly reduced total VTE versus dabigatran (relative risk 0.53); symptomatic VTE was not different between dabigatran and rivaroxaban. There was no significant difference in the rates of major bleeding for patients receiving rivaroxaban or dabigatran. CONCLUSIONS: Based on the indirect comparisons, rivaroxaban was estimated to be more efficacious than dabigatran in the prevention of total VTE after THR and TKR. Our analysis relied upon published data for dabigatran and did not have the advantages of more detailed comparative data obtained directly from a randomized trial, as was the case with rivaroxaban. Further comparative research may be of value, but until available our conclusions represent the best available evidence.

Landiolol hydrochloride for prevention of atrial fibrillation after coronary artery bypass grafting: new evidence from the PASCAL trial.

OBJECTIVE: Atrial fibrillation occurs frequently after cardiac surgery and not only prolongs hospitalization but also influences the prognosis. We investigated whether landiolol hydrochloride, an ultrashort-acting beta-blocker, could reduce postoperative atrial fibrillation in a randomized controlled trial. METHODS: The subjects were 140 patients undergoing coronary artery bypass grafting at the Nihon University School of Medicine. The primary end point was occurrence/non-occurrence of atrial fibrillation up to 1 week postoperatively. Logistic regression analysis was performed to investigate risk factors for atrial fibrillation among preoperative, perioperative, and postoperative variables. RESULTS: Atrial fibrillation occurred in 7 patients (10%) in the landiolol group versus 24 patients (34.3%) in the placebo group; the landiolol group had a significantly lower incidence (P = .0006). Postoperative heart rate was significantly lower in the landiolol group than in the placebo group. On returning to the intensive care unit, the landiolol group had significantly lower inflammatory and ischemic parameters. Medical costs were also significantly lower in the landiolol group. Multivariate analysis revealed that significant risk factors for atrial fibrillation were a European System for Cardiac Operative Risk Evaluation of 10 or more, preoperative non-use of angiotensin receptor blockers, and non-use of landiolol. CONCLUSIONS: Postoperative atrial fibrillation was reduced by treatment with landiolol hydrochloride. Amelioration of ischemia, an anti-inflammatory effect, and inhibition of sympathetic hypertonia by landiolol presumably reduced the occurrence of atrial fibrillation. Hypotension or bradycardia did not develop in any of the patients, indicating the safety of this beta-blocker. These findings suggest that landiolol hydrochloride could be useful in the perioperative management of patients undergoing cardiac surgery.

Rivaroxaban for the prevention of venous thromboembolism: a single technology appraisal.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of rivaroxaban for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from four randomised controlled trials (RCTs) comparing rivaroxaban with enoxaparin [RECORD (Regulation of Coagulation in Orthopedic surgery to pRevent Deep venous thrombosis and pulmonary embolism) 1-4] and three comparing dabigatran with enoxaparin [RE-NOVATE (the prevention of venous thromboembolism after total hip replacement trial), RE-MODEL (the prevention of venous thromboembolism after total knee replacement trial) and RE-MOBILIZE (the prevention of venous thromboembolism after total knee arthroplasty trial)]. The evidence from the four RECORD trials indicates that rivaroxaban had superior efficacy over enoxaparin after total hip replacement (THR) and total knee replacement (TKR). For the composite primary outcome of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE) and death from all causes the relative risk reductions were 70-79% in THR and 31-49% in TKR. Rivaroxaban also had superior efficacy over enoxaparin for the secondary outcome major VTE. Rivaroxaban was not inferior to enoxaparin on the safety outcome of major bleeding. After the correction of some errors found by the ERG, the manufacturer's economic model represented a reasonable model of patients receiving prophylaxis for THR or TKR. In the base-case analyses rivaroxaban dominated both enoxaparin and dabigatran. The incremental costs saved and quality-adjusted life-years (QALYs) gained were small (below 200 pounds and 0.005, respectively, per person). Analyses were conducted sampling from the distributions observed from the RCTs. When all parameters were sampled rivaroxaban dominated enoxaparin in all scenarios except for two, in which enoxaparin produced more QALYs than rivaroxaban and had an incremental cost per QALY gained of 5000 pounds and 8000 pounds respectively. Rivaroxaban dominated dabigatran when RECORD 1 and RECORD 2, individually or pooled, were compared with RE-NOVATE and when all four rivaroxaban RCTs pooled were compared with all three dabigatran RCTs. Dabigatran dominated rivaroxaban comparing RECORD 4 with RE-MODEL and RE-MOBILIZE, and was more cost-effective than rivaroxaban comparing RECORD 3 (incremental cost per QALY gained of rivaroxaban compared with dabigatran of 123,000 pounds) or RECORD 3 and RECORD 4 pooled (incremental cost per QALY gained of dabigatran compared with rivaroxaban of 400 pounds) with RE-MODEL and RE-MOBILIZE. In conclusion, the evidence indicates that rivaroxaban is not inferior to enoxaparin in terms of the primary and secondary outcomes. The submission presents a reasonable estimation of the cost-effectiveness of rivaroxaban compared with enoxaparin and dabigatran, although the uncertainty in the decision has been underestimated. The results are particularly sensitive to any assumed difference in the number of fatal PEs, but the ERG does not believe there is sufficient evidence to support a difference between interventions. The NICE guidance issued as a result of the STA states that: riveroxaban, within its marketing authorisation, is recommended as an option for the prevention of venous thromboembolism in adults having elective THR or elective TKB.

A cost-effectiveness model comparing rivaroxaban and dabigatran etexilate with enoxaparin sodium as thromboprophylaxis after total hip and total knee replacement in the irish healthcare setting.

BACKGROUND: It has been estimated that major orthopaedic surgery has the highest risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) when compared with other surgery. Two new orally active anticoagulants have recently become licensed in Ireland for the primary prevention of venous thromboembolism in adult patients undergoing elective total hip replacement (THR) or total knee replacement (TKR). Rivaroxaban (Xarelto) is a direct factor Xa inhibitor and dabigatran etexilate (Pradaxa) is a prodrug of the active compound dabigatran, which inhibits thrombin. OBJECTIVE: To evaluate the cost effectiveness of rivaroxaban and dabigatran etexilate compared with enoxaparin sodium for the prophylaxis of venous thromboembolism in patients undergoing elective THR and TKR in the Irish healthcare setting. METHODS: The evaluation was conducted from the Irish health-payer perspective. A static decision-tree model was developed with a 180-day post-surgery time horizon. Separate models for the disease states THR and TKR were run to accommodate the different venous thromboembolism risks associated with each procedure. Outcome measures were QALYs and life-years gained (LYG). Costs were valued in euro, year 2008 values. One-way sensitivity analysis of all probabilities in the model was performed. A probabilistic sensitivity analysis using second-order Monte Carlo simulation was performed to determine the probability of cost effectiveness at euro 45,000 per QALY threshold. RESULTS: In the THR base-case model, rivaroxaban dominated both dabigatran etexilate and enoxaparin sodium. The incremental cost-effectiveness ratios for dabigatran etexilate relative to enoxaparin were euro 23,934 per LYG and euro 17,835 per QALY. In the TKR base-case model, rivaroxaban dominated both dabigatran etexilate and enoxaparin sodium. Dabigatran etexilate also dominated enoxaparin sodium. In the one-way sensitivity analysis, the THR model was robust to all but four probability variations; the TKR model was robust to all variations. At a cost-effectiveness threshold of euro 45,000 per QALY, the probability that rivaroxaban was the most cost-effective strategy after THR was 39%, followed by dabigatran etexilate at 32% and enoxaparin sodium at 29%. The probability that rivaroxaban was the most cost-effective strategy after TKR was 46%, followed by dabigatran etexilate at 30% and enoxaparin sodium at 24%. CONCLUSION: Base-case analysis indicates that when both rivaroxaban and dabigatran etexilate are compared with enoxaparin sodium, rivaroxaban is the less costly and more effective option after THR and TKR. Probabilistic sensitivity analysis indicates that rivaroxaban is the most cost-effective strategy at a cost-effectiveness threshold of euro 45,000 per QALY; however, there is uncertainty regarding this strategy being more cost effective than dabigatran etexilate when both are compared with enoxaparin sodium.

Anticoagulation with {blacktriangledown}dabigatran or{blacktriangledown}rivaroxaban.

Anticoagulants such as low molecular weight heparins (LMWH; e.g. enoxaparin) and black triangle downfondaparinux are cost-effective measures for reducing the likelihood of venous thromboembolism (VTE) in patients undergoing surgery.1 black triangle downDabigatran etexilate (Pradaxa-Boehringer Ingelheim)2 and black triangle downrivaroxaban (Xarelto - Bayer) are fixed-dose oral anticoagulants licensed in the European Union (EU) for the prevention of VTE in adults who have undergone or are undergoing elective replacement of the hip or knee joints.2,3 Here, we consider their place for these indications.