Structured benefit-risk assessment for enoxaparin, in the context of its label extension, for the extended treatment of deep vein thrombosis and pulmonary embolism, and prevention of its recurrence in patients with active cancer.

PURPOSE: Guidelines recommend low-molecular-weight heparins (LMWHs) for patients with cancer-associated thrombosis. However, until recently, only dalteparin and tinzaparin were approved in the European Economic Area (EEA) for these patients. This study compares the benefit-risk profile of enoxaparin with dalteparin and tinzaparin for the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrence in adult patients with active cancer. METHODS: A semi-quantitative structured benefit-risk assessment was conducted for the label-extension application of enoxaparin based on the benefit-risk action team descriptive framework: define decision context; determine key benefit and risk outcomes; identify data sources; extract data; interpret results. RESULTS: The key benefits were defined as reduced all-cause mortality and venous thromboembolism (VTE) recurrence (including symptomatic DVT, fatal PE or non-fatal PE); the key risks were major and non-major bleeding of clinical significance, and heparin-induced thrombocytopenia (HIT). Enoxaparin demonstrated comparable effects for the reduction of VTE recurrence and all-cause mortality versus other EEA-approved LMWHs (dalteparin, tinzaparin). There was no evidence of a significant difference between enoxaparin and the comparator groups with regard to incidence of major and non-major bleeding. The data on HIT were too limited to assess the difference between the two groups. CONCLUSIONS: The assessment demonstrated a favourable benefit-risk profile for enoxaparin similar to that of other EEA-approved LMWHs for the treatment of DVT and PE and the prevention of recurrence in patients with active cancer and thus supported the label-extension approval.

Use of direct oral anticoagulants for postoperative venous thromboembolism prophylaxis after surgery for gynecologic malignancies.

Venous thromboembolism is a preventable cause of postoperative mortality in patients undergoing surgery for malignancy. Current standard of care based on international guideline recommends 28 days of extended thromboprophylaxis after major abdominal and pelvic surgery for malignancies with unfractionated heparin or low molecular weight heparin. Direct oral anticoagulants have been approved for the treatment of venous thromboembolism in the general population. This regimen has a significant advantage over other types of anticoagulation regimens, particularly being administered by non-parenteral routes and without the need for laboratory monitoring. In this review, we evaluate the role of direct anticoagulation and provide an update on completed and ongoing clinical trials.

Management of upper extremity deep vein thrombosis in Occitanie: practice assessment.

BACKGROUND: The incidence of upper extremity deep vein thrombosis (UEDVT) is increasing. Its management is sometimes complex and difficult due to its complications and the lack of strong recommendations. The aim was to describe the practice of vascular physicians in Occitanie region in the management of upper extremity deep vein thrombosis. MATERIAL AND METHODS: We used a descriptive observational study in the form of a declarative survey by means of a questionnaire from April to May 2019 among vascular physicians. RESULTS: Of the 142 physicians contacted, 84 responded, with a reply rate of 59.1%. The majority of physicians introduced low-molecular-weight heparin treatment (60.71%) and 29.76% direct oral anticoagulation after a diagnosis of UEDVT. Three months of anticoagulation was chosen by 69% of physicians against 27.4% for a duration of 6 months. Diagnostic work-up included biological risk factors, chest and/or cervical radiography and ultrasonography with dynamic maneuvers. Three quarters of doctors recommended venous compression. A control ultrasonography was performed for 67.86% of patients at one month and at the end of treatment. After the acute phase, 63% of physicians introduced direct oral anticoagulation and 11% recommended venous revascularization. DISCUSSION AND CONCLUSIONS: The mobilization of vascular physicians reflects their interest for this pathology. The management of UEDVT requires specific studies to address therapeutic modalities, the duration of anticoagulation or the place of venous compression in the acute phase.

Prophylaxis of venous thromboembolism in general surgery in Spain. Analysis of a national survey. / Profilaxis del tromboembolismo venoso en cirugía general en España. Análisis de una encuesta nacional.

INTRODUCTION: Venous thromboembolism (VTE) represents a serious postoperative complication that can be prevented by adequate thromboprophylaxis. Surveys provide relevant information about clinician's attitudes and preferences regarding VTE prophylaxis. METHODS: Transversal, descriptive study based on a survey sent to general surgeons members of the Spanish Association of Surgeons (AEC), that included 31 questions regarding postoperative VTE and its prevention, as well as three clinical scenarios. RESULTS: 530 surgeons, 21.8% of the 2,429 invited by electronic mail to participate, completed the survey. Most of the answering clinicians work on in big teaching hospitals, and 28.5% are residents. VTE represents a serious problem for 28% of participants. Although 81% consider that their knowledge on the prevention of postoperative VTE is adequate, a similar percentage recognizes the need for further education. The vast majority (98.7%) use low molecular weight heparins, which are considered the most effective and safe modality, followed by mechanical methods. The Caprini risk assessment score is used by 81% of surgeons, who usually start pharmacological prophylaxis preoperatively. However, there are remarkable differences in the dosing of heparins, timing of initiation, and duration, especially in non-oncologic surgical patients. CONCLUSIONS: Most Spanish surgeons are interested in the prevention of postoperative VTE. Overall, the level of knowledge on thromboprophylaxis is adequate. However, our results indicate that there is a need for better education on relevant practical aspects of prophylaxis that could be achieved by incorporating recommendations from recent guidelines to local hospital-based protocols.

Different strategies for pharmacological thromboprophylaxis for lower-limb immobilisation after injury: systematic review and economic evaluation.

BACKGROUND: Thromboprophylaxis can reduce the risk of venous thromboembolism (VTE) during lower-limb immobilisation, but it is unclear whether or not this translates into meaningful health benefit, justifies the risk of bleeding or is cost-effective. Risk assessment models (RAMs) could select higher-risk individuals for thromboprophylaxis. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of different strategies for providing thromboprophylaxis to people with lower-limb immobilisation caused by injury and to identify priorities for future research. DATA SOURCES: Ten electronic databases and research registers (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, the Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluation Database, Science Citation Index Expanded, ClinicalTrials.gov and the International Clinical Trials Registry Platform) were searched from inception to May 2017, and this was supplemented by hand-searching reference lists and contacting experts in the field. REVIEW METHODS: Systematic reviews were undertaken to determine the effectiveness of pharmacological thromboprophylaxis in lower-limb immobilisation and to identify any study of risk factors or RAMs for VTE in lower-limb immobilisation. Study quality was assessed using appropriate tools. A network meta-analysis was undertaken for each outcome in the effectiveness review and the results of risk-prediction studies were presented descriptively. A modified Delphi survey was undertaken to identify risk predictors supported by expert consensus. Decision-analytic modelling was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained of different thromboprophylaxis strategies from the perspectives of the NHS and Personal Social Services. RESULTS: Data from 6857 participants across 13 trials were included in the meta-analysis. Thromboprophylaxis with low-molecular-weight heparin reduced the risk of any VTE [odds ratio (OR) 0.52, 95% credible interval (CrI) 0.37 to 0.71], clinically detected deep-vein thrombosis (DVT) (OR 0.40, 95% CrI 0.12 to 0.99) and pulmonary embolism (PE) (OR 0.17, 95% CrI 0.01 to 0.88). Thromboprophylaxis with fondaparinux (Arixtra®, Aspen Pharma Trading Ltd, Dublin, Ireland) reduced the risk of any VTE (OR 0.13, 95% CrI 0.05 to 0.30) and clinically detected DVT (OR 0.10, 95% CrI 0.01 to 0.94), but the effect on PE was inconclusive (OR 0.47, 95% CrI 0.01 to 9.54). Estimates of the risk of major bleeding with thromboprophylaxis were inconclusive owing to the small numbers of events. Fifteen studies of risk factors were identified, but only age (ORs 1.05 to 3.48), and injury type were consistently associated with VTE. Six studies of RAMs were identified, but only two reported prognostic accuracy data for VTE, based on small numbers of patients. Expert consensus was achieved for 13 risk predictors in lower-limb immobilisation due to injury. Modelling showed that thromboprophylaxis for all is effective (0.015 QALY gain, 95% CrI 0.004 to 0.029 QALYs) with a cost-effectiveness of £13,524 per QALY, compared with thromboprophylaxis for none. If risk-based strategies are included, it is potentially more cost-effective to limit thromboprophylaxis to patients with a Leiden thrombosis risk in plaster (cast) [L-TRiP(cast)] score of ≥ 9 (£20,000 per QALY threshold) or ≥ 8 (£30,000 per QALY threshold). An optimal threshold on the L-TRiP(cast) receiver operating characteristic curve would have sensitivity of 84-89% and specificity of 46-55%. LIMITATIONS: Estimates of RAM prognostic accuracy are based on weak evidence. People at risk of bleeding were excluded from trials and, by implication, from modelling. CONCLUSIONS: Thromboprophylaxis for lower-limb immobilisation due to injury is clinically effective and cost-effective compared with no thromboprophylaxis. Risk-based thromboprophylaxis is potentially optimal but the prognostic accuracy of existing RAMs is uncertain. FUTURE WORK: Research is required to determine whether or not an appropriate RAM can accurately select higher-risk patients for thromboprophylaxis. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017058688. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

People who have their leg immobilised in a plaster cast or brace following an injury are at risk of developing a blood clot. Sometimes the clot can break up and lodge in the lungs, which can make the person seriously ill. Drugs that thin the blood (anticoagulants) can reduce the risk of blood clots, but they carry a small risk of serious bleeding. This study analysed all published trials of anticoagulants for people with leg immobilisation and found that, without treatment, there was a 1­2% risk of a serious blood clot. This risk was roughly halved by using anticoagulant treatment. These estimates were used in a simulation model of patient treatment and it was found that the benefit of anticoagulants in reducing blood clots (in terms of length and quality of life) outweighed the risks of bleeding. Next, all published studies of risk assessment tools were analysed. Risk assessment tools can be used to predict who is most likely to get a blood clot. There were only a few studies and they had significant weaknesses. The risk assessment tools in the simulation model were evaluated and it was found that the most cost-effective approach was to use a risk assessment tool to select approximately half of the patients for treatment (those at higher risk), while not treating those at lower risk. Treating only the higher-risk patients would be a cost-effective use of NHS resources, compared with treating nobody. Treating everybody, compared with just treating higher-risk patients, would improve outcomes for some patients but would not be a cost-effective use of NHS resources. This study suggests that anticoagulant drugs are an effective and potentially cost-effective way of preventing blood clots in people with leg immobilisation due to injury. Research is needed to determine whether or not risk assessment tools can accurately predict who needs anticoagulant drugs and who does not.

Cost of incorrect application of antithrombotic prophylaxis prior to invasive procedures.

BACKGROUND: We analyze the cost of an incorrect application, by the haematologist, of bridging anticoagulation in patients with low-risk atrial fibrillation (AF) needing interruption of treatment prior to a scheduled invasive procedure. Although not recommended, bridging therapy is widely used, resulting in avoidable costs and increased workload. METHODS: Observational retrospective study. We recorded demographic and clinical data including age, sex, type of procedure, use of bridging therapy with low molecular weight heparin (LMWH), and haemorrhagic complications within 30 days of acenocoumarol withdrawal. RESULTS: Acenocoumarol was stopped in 161 patients, 97 (60%) were male and 64 (40%) female. Average age was 76,11 ± 8,45 years. Procedures included: minor surgical intervention 58 (36%), colonoscopy 61 (38%), gastroscopy 11 (7%), breast biopsy 4 (2.5%), prostate biopsy 4 (2.5%), infiltration 5 (3%), and other 18 (11%). All patients received bridging anticoagulation with LMWH (40 mg enoxaparin per day) 3 days before and 3 days after the procedure (6 doses). We used a total of 966 doses, at €4.5 per unit, resulted in €4347 of total cost. No complications occurred in 156 patients (97%). Haemorrhage was observed in 5 cases: 1 major haemorrhage needing 6 days of hospital stay and transfusion, and 4 minor haemorrhages (2 patients needed emergency attendance and 2 required hospital admission for 3 and 2 days, respectively). The cost of emergency care was €237.36, and the cost of hospital stay was €6860.81 (€623.71 per day, for 11 days). The total cost of the incorrect application of the protocol was €11,445.17. CONCLUSION: Guidelines about bridging anticoagulation in low risk AF patients undergoing scheduled invasive procedures were not followed. This practice increments the complications and supposes an increase in costs besides to an inadequate use of the human resources.

A Review of Two Heparin Prophylaxes for Trauma.

Venous thromboembolism (VTE) prophylaxis has a significant impact on mortality and morbidity in trauma patients. This article reviews 9 published studies that investigate and compare low-dose unfractionated heparin (LDUH) with low-molecular-weight heparin (LMWH) for prophylaxis of VTE in the trauma patient population in terms of efficacy, safety, and cost. There is no difference between LDUH and LMWH for VTE prophylaxis. Four databases were utilized to find 9 relevant studies whose patient population was adult trauma patients: PubMed, CINAHL, EMBASE and Scopus. Two studies found statistically significant differences in deep venous thrombosis, and 3 found differences in pulmonary embolism between LDUH and LMWH. Only 1 study demonstrated a significant difference in bleeding complications between the 2 treatment regimens. Two statedthat using LDUH resulted in remarkable cost savings versus LMWH. The 9 studies all came to different conclusions. Contrary findings may have been affected by population variety, different dosing regimens, various applications of mechanical VTE prophylaxis, and/or different VTE-screening tools. All of the studies had major variances leading to conflicting results, which made this review unable to draw concrete conclusions. Limitations of each study, population variety, and disparity of dosing regimens made it difficult for this review to make recommendations for practice.

Venous Thromboembolism Prophylaxis Strategies for People Undergoing Elective Total Hip Replacement: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: To assess the efficacy and safety of venous thromboembolism prophylaxis in people undergoing elective total hip replacement. METHODS: Systematic review and Bayesian network meta-analyses of randomized controlled trials were conducted for 3 outcomes: deep vein thrombosis (DVT), pulmonary embolism (PE), and major bleeding (MB). MEDLINE, EMBASE, and Cochrane Library (CENTRAL) databases were searched. Study quality was assessed using the Cochrane risk-of-bias checklist. Fixed- and random-effects models were fitted and compared. The median relative risk (RR) and odds ratio (OR) compared with no prophylaxis, with their 95% credible intervals (CrIs), rank, and probability of being the best, were calculated. RESULTS: Forty-two (n = 24 374, 26 interventions), 30 (n = 28 842, 23 interventions), and 24 (n = 31 792, 15 interventions) randomized controlled trials were included in the DVT, PE, and MB networks, respectively. Rivaroxaban had the highest probability of being the most effective intervention for DVT (RR 0.06 [95% CrI 0.01-0.29]). Strategy of low-molecular-weight heparin followed by aspirin had the highest probability of reducing the risk of PE and MB (RR 0.0011 [95% CrI 0.00-0.096] and OR 0.37 [95% CrI 0.00-26.96], respectively). The ranking of efficacy estimates across the 3 networks, particularly PE and MB, had very wide CrIs, indicating high degree of uncertainty. CONCLUSIONS: A strategy of low-molecular-weight heparin given for 10 days followed by aspirin for 28 days had the best benefit-risk balance, with the highest probability of being the best on the basis of the results of the PE and MB network meta-analyses. Nevertheless, there is considerable uncertainty around the median ranks of the interventions.

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

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.

Advances in managing and preventing thromboembolic disease in cancer patients.

PURPOSE OF REVIEW: To update on new data for low-molecular weight heparins (LMWHs) and the direct oral anticoagulants (DOACs) for the treatment and prevention of cancer-associated thrombosis (CAT), to discuss progress with the risk-adaptive management scores (RAMS) and update on increased dose primary thromboprophylaxis (IDPTP). RECENT FINDINGS: In a pooled meta-analysis of 1132 cancer patients who received DOACs vs. vitamin K analogues (VKAs), recurrence of venous thromboembolism (VTE) was reduced from 6.0% on VKA schedules to 3.9% on DOACs. In a randomized trial of warfarin vs. once daily sc. tinzaparin (175 IU/kg), cumulative 6-month VTE incidence reduced from 10.5 to 7.2% [hazard ratio, 0.65 (95% confidence interval, 0.41-1.03); P = 0.07]. Despite early suggestions that DOACs may have a role in CAT, 3-6 months of LMWH remain the standard for initial treatment of CAT. A prospective comparison of RAMS found the Vienna CATS or the PROTECHT scores superior to the Khorana score but concluded that RAMS did not perform well enough to be used in the clinic. An efficacy scale of LMWHs in pancreatic cancer facilitates IDPTP. Practical implementation of IDPTP was needed to control the 40% VTE incidence of the HALO-109-202 study in metastatic pancreatic cancer. SUMMARY: DOACs have some encouraging data, but LMWHs remain the standard for CAT treatment. RAMS generated to predict VTE occurrence or recurrence are still of unproven significance and IDPTP for advanced pancreatic cancer has tools and guidance for implementation.

Similar Clinical Outcomes with Preoperative and Postoperative Start of Thromboprophylaxis in THA: A Register-based Study.

BACKGROUND: Elective THA is associated with a high risk of thromboembolic events. Although these events may be less common now than they were in the past, they can be serious, and most patients undergoing the procedure therefore still receive thromboprophylaxis. However, controversy remains regarding whether to begin thromboprophylaxis before THA or after to best balance the risks of clotting and bleeding. QUESTIONS/PURPOSES: We asked the following questions: (1) Is there a difference in bleeding events with pre- versus postoperative thromboprophylaxis? (2) Is there a difference in thromboembolic episodes after THA between the two regimens? (3) How do the two approaches of thromboprophylaxis influence mortality, readmissions, and other complications? METHODS: We used a population-based followup design with predefined data based on international health codification to assess clinical effects of LMWH prophylaxis initiated before or after THA. We took data limited to primary THAs done in Norway between January 1, 2008, and December 31, 2011, from the Norwegian Arthroplasty Register and the National Patient Register to have necessary data elements to complete the study. The two registers were merged after identifying patients with their 11-digit personal identification number (Social Security number). We obtained data regarding demographics, administrative and surgical details, and episode histories for prophylaxis-related events within 180 days of surgery. A total of 25,163 patients undergoing THA were included for analysis, and 9977(40%) versus 15,186 (60%) patients received pre- and postoperative LMWH, respectively. We performed statistical adjustment for differences in baseline characteristics using multivariate logistic regression. RESULTS: After adjustment for age, sex, operation time, year of surgery, and American Society of Anesthesiologists class, we could not show major differences in bleeding events; (odds ratio [OR], 1.04; 95% CI, 0.88-1.22; p = 0.660), thromboembolic episodes; (OR, 1.03; 95% CI, 0.84-1.27; p = 0.786), or other postoperative clinical complications; (OR, 0.86; 95% CI, 0.76-0.99; p = 0.034), with the two regimens. Six-month mortality was similar, (OR, 0.76; 95% CI, 0.56-1.05; p = 0.093), and the readmission rate was higher in the preoperative group; (OR, 0.92; 95% CI, 0.85-0.97; p = 0.016). CONCLUSIONS: The risk for postoperative complications seems to be comparable whether LMWH prophylaxis is initiated before or after THA. The postoperative approach reduces costs, decreases risks related to neuraxial anesthesia, and facilitates same-day admissions. Methods for individual risk assessment including laboratory tests would be feasible. LEVEL OF EVIDENCE: Level III, therapeutic study.

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.

Graduated Compression Stockings as an Adjunct to Low Dose Low Molecular Weight Heparin in Venous Thromboembolism Prevention in Surgery: A Multicentre Randomised Controlled Trial.

BACKGROUND: The evidence base upon which current global venous thromboembolism (VTE) prevention recommendations have been made is not optimal. The cost of purchasing and applying graduated compression stockings (GCS) in surgical patients is considerable and has been estimated at £63.1 million per year in England alone. OBJECTIVE: The aim was to determine whether low dose low molecular weight heparin (LMWH) alone is non-inferior to a combination of GCS and low dose LMWH for the prevention of VTE. METHODS: The randomised controlled Graduated compression as an Adjunct to Pharmacoprophylaxis in Surgery (GAPS) Trial (ISRCTN 13911492) will randomise adult elective surgical patients identified as being at moderate and high risk of VTE to receive either the current "standard" combined thromboprophylactic LMWH with GCS mechanical thromboprophylaxis, or thromboprophylactic LMWH pharmacoprophylaxis alone. To show non-inferiority (3.5% non-inferiority margin) for the primary endpoint of all VTE within 90 days, 2236 patients are required. Recruitment will be from seven UK centres. Secondary outcomes include quality of life, compliance with stockings and LMWH, overall mortality, and GCS or LMWH related complications (including bleeding). Recruitment commenced in April 2016 with the seven UK centres coming "on-line" in a staggered fashion. Recruitment will be over a total of 18 months. The GAPS trial is funded by the National Institute for Health Research Health Technology Assessment in the UK (14/140/61).

[Economic consequences of biological monitoring and medical complications of injectable anticoagulants in France]. / Conséquences économiques du suivi biologique et des complications médicales en lien avec l'utilisation des anticoagulants injectables en France.

AIM: To assess the frequency of platelet monitoring and bleeding risks associated with the use of injectable anticoagulants in a real life setting and to estimate the associated costs. METHOD: An analysis of the 2013 data from a random sample of ≈600,000 patients registered in the French National Health Insurances reimbursement database was conducted to identify platelet counts performed during injectable anticoagulants exposure period and treatment interruptions due to heparin-induced thrombocytopenia or transfusion. Events were then valued to establish associated costs. RESULTS: Overall 15,985 adult patients representing a cumulated injectable anticoagulants exposure time of 12,264 months were selected. Treatment sequences involved unfractionated heparin (2.8%), low molecular weight heparin (86.9%), and fondaparinux (13.1%). Patients treated with unfractionated heparin were older (77 vs. 57 and 59 years) with longer treatment duration (32.6 vs. 25.1 and 21 days). After statistical adjustment, the average monthly number of platelet counts was 1.36-fold lower in patients treated with fondaparinux compared to low molecular weight heparin (P<0.0001). No difference was found between low molecular weight heparin and fondaparinux regarding the incidence of bleeding with transfusion (P=0.76) or hospitalized thrombocytopenia (P=0.82). Extrapolated for the whole country, the estimated costs for biological monitoring were € 21.6 million for low molecular weight heparin and € 0.9 million for fondaparinux. CONCLUSION: Significantly fewer platelet counts were performed among patients treated with fondaparinux than among patients receiving low molecular weight heparin without additional bleeding risk. This finding should be taken into account when assessing the costs of such treatments.

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.

Immediate post-procedure bridging with unfractioned heparin versus low molecular weight heparin in patients undergoing radiofrequency ablation for atrial fibrillation with an interrupted oral anticoagulation strategy.

PURPOSE: Many centers perform catheter ablation for atrial fibrillation (AF) with periprocedural interruption of oral vitamin K antagonists. In this scenario, the optimal post-procedural anticoagulation strategy is still under debate. We sought to compare the incidence of major complications associated with post-procedural use of low molecular weight heparin (LMWH) versus unfractioned heparin (UFH) as a bridge to reinitiation of oral anticoagulation after an AF ablation procedure. METHODS: We retrospectively reviewed medical history data of all patients undergoing catheter ablation for AF at three Spanish referral centers between January 2009 and January 2014. A total of 702 patients were included in the analysis. We compared the incidence of major complications (a combination of major bleeding and thromboembolic events) between patients receiving UFH (291) and those receiving LMWH (411) after the procedure. RESULTS: The overall incidence of major complications was 4.1%, including five thromboembolic events (0.7%) and 24 major bleeding events (3.4%), with no significant differences in patients treated with LMWH vs. UFH (2.9 vs. 4.1%; P = NS). The presence of peripheral vascular disease emerged as the only independent predictor of major complications (adjusted odds ratio (OR) 9.1; confidence interval (CI) 95% 1.7-49.3; P < 0.01). CONCLUSIONS: Immediate post-procedural bridging with UFH or with LMWH are equally safe strategies in patients undergoing catheter ablation for AF in whom oral anticoagulation is interrupted for the procedure. Due to its greater simplicity of use, LMWH may be the preferred option. The presence of peripheral vascular disease is a potent predictor of major post-procedural complications.

[Prevalence, indication and compliance with the recommendations of prescription of low molecular weight heparin in oncology]. / Prévalence, indication et conformité aux recommandations de prescription d'héparine de bas poids moléculaire en oncologie.

INTRODUCTION: Venous thromboembolism is a common complication in cancer and is the second cause of death below infection. Low molecular weight heparin is the gold standard in venous thromboembolism during cancer. This work aimed to evaluate the prevalence of prescription of low molecular weight heparin used at curative dose and the compliance of our practices with the recommendations. METHODS: A retrospective study was led over a 3-month period, on adult patients suffering from venous thromboembolism who had received low molecular weight heparin at curative dose. RESULTS: A 4% prevalence of prescription of low molecular weight heparin at curative doses has been reported. The results showed an incidental discovery of venous thromboembolism on routine restaging scans in 64% cases. The most found indication was the treatment of deep vein thrombosis (51% cases). According to the dosage, overall compliance of prescription is estimated at 55%. DISCUSSION: The incidental discovery rate (64%) is consistent with the literature that confirms the high incidence of asymptomatic thrombosis. The rate of non-compliant prescriptions could result from a lack of re-evaluation and adjustment of dosages. These results confirm the need to educate practitioners in diagnosing and managing venous thromboembolism.

A feasibility study to inform the design of a randomised controlled trial to identify the most clinically effective and cost-effective length of Anticoagulation with Low-molecular-weight heparin In the treatment of Cancer-Associated Thrombosis (ALICAT).

BACKGROUND: Venous thromboembolism is common in cancer patients and requires anticoagulation with low-molecular-weight heparin (LMWH). Current data recommend LMWH for anticoagulation as far as 6 months, yet guidelines recommend LMWH beyond 6 months in patients who have ongoing or active cancer. This recommendation, based on expert consensus, has not been evaluated in a clinical study. OBJECTIVES: (1) To identify the most clinically and cost-effective length of anticoagulation with LMWH in the treatment of cancer-associated thrombosis (CAT); (2) to identify practicalities of conducting a full randomised controlled trial (RCT) with regard to recruitment, retention and outcome measurement; and (3) to explore the barriers for progressing to a full RCT. DESIGN: The Anticoagulation with Low-molecular-weight heparin In the treatment of Cancer-Associated Thrombosis (ALICAT) trial is a randomised, multicentre, feasibility mixed-methods study with three components: (1) a RCT comparing ongoing LMWH treatment for CAT with cessation of LMWH at 6 months' treatment (current licensed practice) in patients with locally advanced or metastatic cancer, consulted in three clinical settings (haematology outpatients, oncology outpatients and primary care); (2) a nested qualitative study, including focus groups with clinicians to investigate attitudes for recruiting to the study and identify the challenges of progressing to a full RCT, and semistructured interviews with patients and relatives to explore their attitudes towards participating in the study, and potential barriers and concerns to participation; and (3) a UK-wide survey exercise to develop a classification and enumeration system for the CAT models and pathways of care. SETTING: A haematology outpatients department, an oncology outpatients department and primary care. PARTICIPANTS: Patients with ongoing active or metastatic cancer who have received 6 months of LMWH for CAT. INTERVENTIONS: Ongoing LMWH treatment for CAT versus cessation of LMWH at 6 months' treatment in patients with locally advanced or metastatic cancer. MAIN OUTCOME MEASURES: (i) The number of eligible patients over 12 months; (ii) the number of recruited patients over 12 months (target recruitment rate of 30% of eligible patients); and (iii) the proportion of randomised participants with recurrent venous thromboembolisms (VTEs) during follow-up. RESULTS: Following several delays in setting up the RCT component of the study, 5 out of 32 eligible patients consented to be randomised to the RCT suggesting progression to a full RCT was not feasible. Reasons for non-consenting were primarily based on a fixed preference for continuing or discontinuing treatment after 6 months of anticoagulation, and a fear of randomisation to their non-preferred option. Views were largely influenced by patients' initial experience of CAT. Focus groups with clinicians revealed that they would be reticent to recruit to such a study as they had fixed views of best management despite the lack of evidence. Patient pathway modelling suggested that there is a broad heterogeneity of practice with respect to CAT management and co-ordination, with no consensus on which specialty should best manage such cases. CONCLUSIONS: The results of the RCT reflect recruitment from the oncology site only and provide no recruitment data from haematology centres. However, it is unlikely that these other sites would have access to more eligible patients. The management of cancer-associated thrombosis beyond 6 months will remain a clinical challenge. As it is unlikely that a prospective study will successfully recruit, other strategies to accrue relevant data are necessary. Currently the LONGHEVA (Long-term treatment for cancer patients with deep-venous thrombosis or pulmonary embolism) registry is in development to prospectively evaluate this important and common clinical scenario. STUDY REGISTRATION: This study is registered as clinical trials.gov number NCT01817257 and International Standard Randomised Controlled Trial Number (ISRCTN) 37913976. FUNDING DETAILS: Funding for the ALICAT trial was provided by the Health Technology Assessment programme (10/145/01) in response to a themed funding call. The study was designed in accordance with the initial funding brief and feedback from the review process.