Overall Effectiveness of Rivaroxaban in Patients with Pulmonary Embolism.

PURPOSE: Due to limited evidence on the impact of rivaroxaban in clinical practice, we compared the effectiveness of rivaroxaban versus standard of care (SOC) among patients in the Veterans Health Administration. METHODS: Adult patients with continuous enrollment in a health plan with medical and pharmacy benefits for ≥12 months before and ≥3 months after an inpatient diagnosis of pulmonary embolism (PE) between October 1, 2011, and June 30, 2015, and a prescription claim for an anticoagulant during the index hospitalization, were included. SOC drugs were low-molecular-weight heparin, unfractionated heparin, and warfarin. Propensity score matching was used in comparing PE-related outcomes (recurrent venous thromboembolism, major bleeding, and death), hospital-acquired complications (HACs), health care resource utilization, and costs among patients receiving SOC versus rivaroxaban. We defined net clinical benefit as 1 minus the combined rate of PE-related outcomes and HACs. FINDINGS: Among 6746 patients with PE, 208 received rivaroxaban, 4641 received SOC and 1897 received other anticoagulants. Most (95%) were male; 22% were black. After 1:3 propensity score matching, there were 203 rivaroxaban and 609 SOC patients. During the 90-day follow-up, rivaroxaban users had similar rates of PE-related outcomes, but fewer had experienced at least 1 HAC (10.3% vs 15.9%; P = 0.0506), resulting in better net clinical benefit (82.8% vs 71.1%; P = 0.001). Rivaroxaban users had fewer outpatient visits per patient (17.0 vs 19.9; P = 0.0005), a similar rehospitalization rate (0.2 vs 0.3; P = 0.084), lesser inpatient costs (US $3501 vs $6189; P < 0.0001), lesser inpatient costs and lesser total costs ($10,545 vs $14,192; P = 0.0002). When the sample was limited to patients with low-risk PE, we found similar patterns. IMPLICATIONS: Patients with PE prescribed rivaroxaban had similar PE-related outcomes, but fewer HACs and lesser total costs, than did patients on SOC.

Rivaroxaban versus Heparin Bridging to Warfarin Therapy: Impact on Hospital Length of Stay and Treatment Costs for Low-Risk Patients with Pulmonary Embolism.

STUDY OBJECTIVE: To compare hospital length of stay (LOS) and hospital treatment costs in low-risk patients with pulmonary embolism (PE) anticoagulated with rivaroxaban or heparin bridging to warfarin therapy. DESIGN: Retrospective review of electronic health records and hospital billing records. SETTING: Large, teaching hospital in the northeastern United States. PATIENTS: One hundred ninety adults with objectively confirmed acute PE presenting to the emergency department between November 1, 2012, and May, 12, 2015, who were classified as low risk of early mortality and received anticoagulation with either rivaroxaban or heparin (i.e., unfractionated heparin or low-molecular-weight heparin) bridging to warfarin therapy were included in the analysis. Patients were identified as low risk by at least one of the following prediction rules: simplified Pulmonary Embolism Severity Index (sPESI; 115 patients), Hestia criteria (87 patients), or In-hospital Mortality for Pulmonary Embolism using Claims Data (IMPACT; 108 patients); these were not mutually exclusive, as patients could be classified as low risk by more than one risk stratification tool. MEASUREMENTS AND MAIN RESULTS: We divided low-risk patients identified by each prediction rule into two cohorts: those receiving rivaroxaban (allowing ≤ 2 days of prior heparin use) or heparin bridging to warfarin therapy. The primary end points for this study were LOS (number of days from the patient's arrival at our institution until discharge) and total hospital treatment costs (our institution's actual costs to provide treatment) for the index PE hospital encounter. Using multivariable generalized linear model regression (gamma-distributed error and log-link), we estimated differences in LOS and hospital costs (in 2015 U.S. dollars) between the two cohorts after covariate adjustment. Rivaroxaban was associated with significantly shorter adjusted LOS (range -2.1 to -4.3 days) and significantly lower index hospital costs (range -$3835 to -$7094) versus heparin bridging to warfarin, regardless of the prediction rule used to identify low-risk patients. CONCLUSION: Among low-risk PE patients identified by using sPESI, Hestia or IMPACT, rivaroxaban was associated with significantly shorter LOS and lower hospital treatment costs versus heparin bridging to warfarin.

Bioenergetic gain of citrate anticoagulated continuous hemodiafiltration--a comparison between 2 citrate modalities and unfractionated heparin.

PURPOSE: To determine bioenergetic gain of 2 different citrate anticoagulated continuous hemodiafiltration (CVVHDF) modalities and a heparin modality. MATERIALS AND METHODS: We compared the bio-energetic gain of citrate, glucose and lactate between 29 patients receiving 2.2% acid-citrate-dextrose with calcium-containing lactate-buffered solutions (ACD/Ca(plus)/lactate), 34 on 4% trisodium citrate with calcium-free low-bicarbonate buffered fluids (TSC/Ca(min)/bicarbonate), and 18 on heparin with lactate buffering (Hep/lactate). RESULTS: While delivered CVVHDF dose was about 2000 mL/h, total bioenergetic gain was 262 kJ/h (IQR 230-284) with ACD/Ca(plus)/lactate, 20 kJ/h (8-25) with TSC/Ca(min)/bicarbonate (P < .01) and 60 kJ/h (52-76) with Hep/lactate. Median patient delivery of citrate was 31.2 mmol/h (25-34.7) in ACD/Ca(plus)/lactate versus 14.8 mmol/h (12.4-19.1) in TSC/Ca(min)/bicarbonate groups (P < .01). Median delivery of glucose was 36.8 mmol/h (29.9-43) in ACD/Ca(plus)/lactate, and of lactate 52.5 mmol/h (49.2-59.1) in ACD/Ca(plus)/lactate and 56.1 mmol/h (49.6-64.2) in Hep/lactate groups. The higher energy delivery with ACD/Ca(plus)/lactate was partially due to the higher blood flow used in this modality and the calcium-containing dialysate. CONCLUSIONS: The bioenergetic gain of CVVHDF comes from glucose (in ACD), lactate and citrate. The amount substantially differs between modalities despite a similar CVVHDF dose and is unacceptably high when using ACD with calcium-containing lactate-buffered solutions and a higher blood flow. When calculating nutritional needs, we should account for the energy delivered by CVVHDF.

Cost-effectiveness of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor in the treatment of acute ST-segment elevation myocardial infarction.

OBJECTIVE: To assess the cost-effectiveness of bivalirudin versus heparin and glycoprotein IIb/IIIa inhibitor (H-GPI) in patients undergoing primary percutaneous coronary intervention (PPCI) for acute ST-segment elevation myocardial infarction (STEMI), from a UK health service perspective. DESIGN: Cost-utility analysis with life-long time horizon. MAIN OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness. METHODS: Event risks and medical resource use data derived from the HORIZONS-AMI trial were entered into a decision analytic model. Clinical events until the end of year 1 (main model) or year 3 (alternative model) were modelled in detail. Adjustments were applied to approximate UK routine practice characteristics. Life expectancy of 1-year or 3-year survivors, health-state utilities, initial hospitalisation length of stay in the comparator strategy and unit costs were based on UK sources. Costs and effects were discounted at 3.5%. RESULTS: The main model predicted bivalirudin and H-GPI patients to survive 11.52 and 11.35 (undiscounted) years on average, respectively, and to accrue 6.26 and 6.17 QALYs. Patient lifetime costs were £267 lower in the bivalirudin strategy (£12 843 vs £13 110). Extensive sensitivity and scenario analyses confirmed these results to be robust. In probabilistic analysis, quality-adjusted survival was higher and costs were lower with bivalirudin in 95.0% of simulation runs. In 99.2%, cost-effectiveness was better than £20 000 per QALY gained. Results from the alternative model were fully consistent. CONCLUSION: The use of bivalirudin instead of H-GPI in STEMI patients undergoing PPCI is cost-effective, and offers a high probability of dominance. Background treatment with aspirin and clopidogrel is assumed.

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.

Cost-minimization analysis of low-molecular-weight heparin (dalteparin) compared to unfractionated heparin for inpatient treatment of cancer patients with deep venous thrombosis.

GOALS: Low-molecular-weight heparin (LMWH) has shown to be as effective as unfractionated heparin (UFH) in the treatment of deep venous thrombosis (DVT). Although the acquisition cost of LMWH is significantly greater than that of UFH, we hypothesized that once-daily dalteparin, a LMWH, could reduce treatment costs of cancer patients with DVT by eliminating anticoagulation monitoring and shortening hospitalization. PATIENTS AND METHODS: We developed a cost-minimization model by using outcomes and resource utilization data from two retrospective matched cohorts of cancer patients who, between 1994 and 1999, were hospitalized at our comprehensive cancer center for treatment of DVT with either LMWH ( n=21) or UFH ( n=168). We assumed all LMWHs and UFH to be equally effective. The total costs for the dalteparin strategy and the UFH strategy were calculated in year 2003 U.S. dollars, from the provider's perspective, by multiplying the number of resources used for inpatient treatment of DVT by their unit costs. RESULTS: The mean total cost for inpatient care was $3,383 US dollars (95% CI= $2,683- $4,083) for dalteparin and $4,952 US dollars (95% CI=$4,718-$5,185) for UFH. Substantial savings resulted from shorter hospitalization among the dalteparin-treated patients (mean 3.19 versus 5.22 days). Sensitivity analysis did not change the conclusion that dalteparin is less expensive than UFH. CONCLUSIONS: Savings realized from less anticoagulant monitoring and shorter hospitalization offset the higher acquisition cost of dalteparin. The dalteparin strategy is less expensive than the UFH strategy for the inpatient treatment of DVT among cancer patients.

[Comparison of ambulatory and inpatient treatment of acute deep venous thrombosis of the leg: subjective and economic aspects]. / Vergleich von ambulanter und stationärer Behandlung der akuten tiefen Beinvenenthrombose: subjektive und ökonomische Aspekte.

The frequency of clinical recurrence and pulmonary embolism in patients with acute deep venous thrombosis is reduced to the same extent by hospital treatment (with unfractionated heparin) as by treatment at home (with low-molecular-weight heparin). Very few data on subjective parameters of effectiveness have been published. We performed a prospective randomized trial comparing outpatient with in-hospital treatment in 28 patients. Six clinical and quality-of-life related parameters of effectiveness were assessed quantitatively: clinical course (with a score system), pain of venous congestion of the calf muscles (with Lowenberg's test), subjective perception of pain and general well-being (with visual analogue scales), satisfaction with the care provided, and absence from work. Subjective effectiveness was compared with the costs of each form of treatment. Outpatient treatment was significantly more effective than in-hospital treatment with regard to the objective parameters. It was, however, associated with less well-being and more pain than in-hospital treatment. The discrepancy is explained by eventually insufficient adjuvant treatment measures (which consisted of external leg compression by stockings and forced walking) and by anxiety brought on by the information that potentially lethal pulmonary embolism could occur despite anticoagulant therapy. Outpatient treatment was less costly. On the average and per patient it was CHF 3944 less expensive than treatment in hospital. An estimation reveals that the Swiss health care system would save about CHF 25 million per year if the 85% of patients with deep-vein thrombosis suitable for home care were given this form of treatment. We conclude that outpatient management is subjectively cost-effective but should be optimised to eliminate certain drawbacks associated with it.

Treatment of proximal vein thrombosis with subcutaneous low-molecular-weight heparin vs intravenous heparin. An economic perspective.

BACKGROUND: Subcutaneous low-molecular-weight heparin is at least as effective and safe as classic intravenous heparin therapy for the treatment of proximal vein thrombosis. Anticoagulant monitoring is not required with low-molecular-weight heparin. OBJECTIVE: To perform an economic evaluation of these therapeutic approaches by comparing cost and effectiveness. PATIENTS AND METHODS: A randomized trial in 432 patients with proximal vein thrombosis that compared intravenous heparin and low-molecular-weight heparin with objective documentation of clinical outcomes provided the opportunity to perform an analysis of cost-effectiveness to rank these alternative therapies in terms of both their cost and effectiveness. The economic viewpoint of this analysis was that of a third-party payer (ie, a ministry of health in Canada or an insurance company in the United States). RESULTS: In the intravenous heparin-treated group, the cost incurred for 100 patients was $414,655 (Canadian dollars) or $375,836 (US dollars), with a frequency of objectively documented venous thromboembolism of 6.9%. In the low-molecular-weight heparin-treated group, the cost incurred for 100 patients was $399,403 (Canadian dollars) or $335,687 (US dollars), with a frequency of objectively documented venous thromboembolism of 2.8%, thus providing a cost saving of $15,252 (Canadian dollars) or $40,149 (US dollars). Multiple sensitivity analyses were performed, and these procedures did not alter the findings of the study. CONCLUSIONS: The findings indicate that low-molecular-weight heparin therapy is at least as effective and safe but less costly than intravenous heparin treatment. The potential for outpatient therapy in up to 37% of patients who are receiving low-molecular-weight heparin would substantially augment the cost saving.

Cost effectiveness of adjuvant intraportal chemotherapy in patients with colorectal cancer.

Recent studies have shown that the analysis of published survival curves allows cost-effectiveness evaluations in which two treatments are compared with each other in terms of cost per life-year saved. In patients with colorectal cancer, the administration of adjuvant intraportal chemotherapy (with mitomycin and fluorouracil) has been reported to improve long-term survival in comparison with patients who are not given this treatment. To assess the pharmacoceconomic profile of this adjuvant chemotherapy, we carried out an incremental cost-effectiveness analysis in which we used the Gompertz model to estimate lifetime patient years gained by patients given this chemotherapy in comparison with controls. Using the data of a published controlled long-term trial involving 252 patients treated with intraportal chemotherapy and 253 controls who were given no such therapy, we estimated that the adjuvant treatment improved life expectancy by 89 discounted patient years (or 218 undiscounted patient years) every 100 patients. Cost of chemotherapy was calculated as $107,720 for every 100 patients. On the basis of these data, the administration of adjuvant intraportal chemotherapy was found to imply an incremental cost of $1,210 per discounted life-year saved or $494 per undiscounted life-year saved. The cost-effectiveness ratio of adjuvant intraportal chemotherapy in patients with colorectal cancer seems to be particularly favorable in comparison with estimates of cost per life-year saved previously obtained in many other areas of pharmacological intervention. Even though systemic fluorouracil + levamisole is the form of adjuvant chemotherapy most widely used in these patients, intraportal chemotherapy has the best cost-effectiveness profile.