Choosing the right heparin prophylaxis strategy in medical patients at risk for developing VTE: an evidence-based approach

Many acutely ill medical patients are at significant risk for developing venous thromboembolism (VTE) during hospitalization. Venous thromboembolism risk arises from both the presenting clinical condition as well as predisposing risk factors, such as advanced age. Thromboprophylaxis is underprescribed in these patients. Thrombotic risk assessment could encourage the prescribing of thromboprophylaxis and, therefore, improve patient protection against VTE. Current guidelines from the American College of Chest Physicians and the International Union of Angiology (IUA) recommend thromboprophylaxis with low-dose unfractionated heparin (UFH), a low-molecular-weight heparin (LMWH), or fondaparinux for acutely ill medical patients with VTE risk factors. However, the optimal dose regimen for UFH is unclear. The 2006 evidence-based guidelines from the IUA recommend a 3-times-daily dose regimen for UFH. However, UFH is usually administered twice daily despite a lack of evidence for the superiority of this regimen. Both heparin-induced thrombocytopenia and bleeding are associated with UFH, and to a lesser degree with alternative anticoagulants, such as the LMWHs. If utilized, an appropriate prophylaxis regimen in medical patients can reduce the risk of VTE and its burden.     

‘Efficiency’ Watchword Comes to the Fore

Abstract

Many acutely ill medical patients are at significant risk for developing venous thromboembolism (VTE) during hospitalization. Venous thromboembolism risk arises from both the presenting clinical condition as well as predisposing risk factors, such as advanced age. Thromboprophylaxis is underprescribed in these patients. Thrombotic risk assessment could encourage the prescribing of thromboprophylaxis and, therefore, improve patient protection against VTE. Current guidelines from the American College of Chest Physicians and the International Union of Angiology (IUA) recommend thromboprophylaxis with low-dose unfractionated heparin (UFH), a low-molecular-weight heparin (LMWH), or fondaparinux for acutely ill medical patients with VTE risk factors. However, the optimal dose regimen for UFH is unclear. The 2006 evidence-based guidelines from the IUA recommend a 3-times-daily dose regimen for UFH. However, UFH is usually administered twice daily despite a lack of evidence for the superiority of this regimen. Both heparin-induced thrombocytopenia and bleeding are associated with UFH, and to a lesser degree with alternative anticoagulants, such as the LMWHs. If utilized, an appropriate prophylaxis regimen in medical patients can reduce the risk of VTE and its burden.     

A case-control study of seated immobility at work as a risk factor for venous thromboembolism

OBJECTIVE: To determine the relative risk of prolonged seated immobility at work in patients with a deep vein thrombosis (DVT) or pulmonary embolism (PE). DESIGN: A case-control study: cases and controls completed an interviewer-administered questionnaire to obtain information on risk factors for venous thromboembolism (VTE), including prolonged seated immobility at work. Univariate and multivariate logistic regression was used to determine the association between predicted variables and the probability of being a case or control. PARTICIPANTS: Cases were patients<65 years old attending the Wellington Hospital Outpatient VTE Clinic following hospital discharge for DVT and/or PE. Controls were patients<65 years old admitted to the Coronary Care Unit at Wellington Hospital. SETTING: The Wellington Hospital Outpatient VTE Clinic and Coronary Care Unit. MAIN OUTCOME MEASURES: Odds ratio of VTE for prolonged seated immobility. RESULTS: There were 97 cases (53 DVT, 29 PE, 15 DVT and PE), and 106 controls. In the multivariate analysis the odds ratio of VTE for prolonged seated immobility at work was 1.8 (95% CI 0.71-4.8). The maximum number of hours seated at work was associated with VTE, with the risk increasing by 10% per hour longer seated (odds ratio 1.1, 95% CI 1.0-1.2). The maximum number of hours seated at work without getting up was associated with VTE, with the risk increasing by 20% per hour longer seated (odds ratio 1.2, 95% CI 0.96-1.6). CONCLUSIONS: This study provides preliminary evidence that prolonged seated immobility at work may represent a risk factor for VTE.     

Rates of hospitalization among patients with deep vein thrombosis before and after the introduction of rivaroxaban

Background. Compared to warfarin, the non-vitamin K antagonist oral anticoagulant rivaroxaban may have advantages in treating patients with venous thromboembolism, because injectable bridging therapy and routine laboratory monitoring are not required. The objective of this study was to compare the rate of hospitalization in patients treated with rivaroxaban after its introduction with what it would have been before the introduction of rivaroxaban. Methods. A retrospective claims analysis was conducted using the MarketScan Hospital Drug Database from January 2011 to December 2013. Adult patients with a primary diagnosis of deep vein thrombosis (DVT) treated with rivaroxaban or low-molecular-weight heparin (LMWH) bridged to warfarin during the first day of an evaluation at a hospital were identified. Based on propensity-score methods, historical LMWH/warfarin patients (i.e., patients who received LMWH/warfarin before the approval of rivaroxaban) were matched 4:1 to rivaroxaban patients, and the rates of hospitalization were compared. Results. All rivaroxaban-treated patients (n = 134) in the database were well matched with four historical LMWH/warfarin-treated patients (n = 536). Among the rivaroxaban cohort, 60% of the patients were admitted to the hospital, compared to 82% of the historical patients treated with LMWH/warfarin in the matched cohort. The difference was statistically significant and corresponded to a 27% reduction in hospital admissions (rate ratio [95% confidence interval]: 0.73 [0.62–0.84]). Hospital admission rates adjusted for time-trend analyses also led to similar results. Conclusion. The availability of rivaroxaban significantly reduced the hospitalization rate in patients with DVT treated with rivaroxaban compared to what it would have been if only LMWH/warfarin were available.     

Major bleeding rates after prophylaxis against venous thromboembolism: systematic review, meta-analysis, and cost implications

OBJECTIVES: The frequency and consequences of major bleeding associated with anticoagulant prophylaxis for prevention of venous thromboembolism is examined. METHODS: We conducted a systematic review and meta-analysis of controlled trials that reported rates of major bleeding after pharmaceutical thromboprophylaxis in patients undergoing major orthopedic surgery. Thromboprophylactic agents were divided into four groups: warfarin/other coumarin derivatives (WARF), unfractionated heparin (UFH), low molecular weight heparin (LMWH), and pentasaccharide (PS). Meta-analysis was conducted comparing LMWH with each of WARF, UFH, and PS. The frequency of re-operation due to major bleeding was reviewed and combined with published costs to estimate the mean cost of managing major bleeding events in these patients. RESULTS: Twenty-one studies including 20,523 patients met inclusion criteria for the meta-analysis. No evidence of significant between-trial heterogeneity in risk ratios was found. Combined (fixed effects) relative risks (RR) of major bleeding compared with LMWH were WARF--RR 0.59 (95 percent confidence interval [CI], 0.44-0.80); UFH--RR 1.52 (95 percent CI, 1.04-2.23); PS--RR 1.52 (95 percent CI, 1.11-2.09). Seventy-one studies including 32,433 patients were included in the review of consequences of major bleeding. We estimated that the average cost of major bleeding is 113 dollars per patient receiving thromboprophylaxis. CONCLUSIONS: LMWH results in fewer major bleeding episodes than UFH and PS but more than WARF. These events are costly and clinically important.     

术后静脉血栓栓塞症

目的了解术后静脉血栓栓塞患者的特点,为临床预防和治疗提供参考。方法选取1997年1月-2004年8月诊治的47例术后下肢深静脉血栓形成的患者,并对资料作一回顾性分析。结果关节、脊柱、创伤手术是引起术后静脉血栓栓塞的高危因素;术后下肢深静脉血栓形成的发生有两个高峰:术后3 d内和10 d后;肺栓塞占静脉血栓栓塞患者的27．7％,均见于中央型和/或混合型下肢深静脉血栓形成患者。单纯抗凝治疗下肢深静脉血栓痊愈10例(21．3％),显效 18例(38．3％),有效19例(40．4％);肺栓塞者痊愈5例(38．5％),显效4例(30．8％),有效4例 (30．7％)。下肢深静脉血栓复发者5例,肺栓塞复发者2例,瓣膜功能未恢复者3例。结论 (1) 静脉血栓栓塞症高危患者需行手术和发生创伤时,应采取措施预防静脉血栓栓塞症。(2)注意术后迟发性下肢深静脉血栓形成。(3)两种影像学辅助检查相互配合可提高静脉血栓栓塞症的诊断。     

Outcomes related to variation in hospital pulmonary embolus observation stay utilization

Objectives: To characterize hospital variation in use of observation stays to manage pulmonary embolism (PE) and its association with subsequent outcomes.

Methods: We performed a cross-sectional study of hospitals reporting ≥75 PE encounters (emergency department, observation stay or inpatient admission) using Premier data from 11/2012-3/2015. We included hospital encounters for adults with a primary diagnosis of PE (415.1x), ≥1 diagnostic test claim for PE on day 0-2 and evidence of PE treatment. Hospitals were divided into tertiles (Ts) based on the proportion of all PE encounters managed as an observation stay. The association between observation stay utilization and the proportion of PE encounters resulting in in-hospital death or re-admission within the same or subsequent 2-months were compared across Ts using a generalized estimating equation adjusted for individual encounter disease severity.

Results: Observation PE management increased over the study period (1.9%-5.4%; Pearson’s r = 0.88, p < 0.001). Of all hospitals reporting ≥1 PE encounter, 255 had ≥75 encounters (representing a total of 38,172 PE encounters) and were included in the analysis. Individual hospital observation use for PE management varied from 0%-33.9%. Mean hospital rates of PE observation stay by T were T1 = 0.1%, T2 = 2.2% and T3 = 7.9%. Hospitals that used observation stays most frequently (T3) were more likely in the South or Mid-west (p < 0.001), to be a teaching hospital (p = 0.03) and less likely to serve an urban population (p = 0.02). Hospitals in T3 (n = 11,780 encounters) were not associated with a statistically significant increased risk of in-hospital death (2.3% vs. 2.1%-2.6%) or all-cause (4.7% vs. 5.1%-5.4%), venous thromboembolism-(1.4% vs. 1.8%-2.0%) or major bleeding (0.3% vs. 0.2-0.3%)-related re-admission in the same or subsequent 2-months compared to T1 (n = 12,940 encounters) and T2 (n = 13,452 encounters).

Conclusion: PE management via observation stays has increased over recent years. Hospitals more frequently utilizing observation stays may not experience increased negative outcomes, such as re-admission.     

Venous thromboembolism in adult hospitalizations - United States, 2007-2009

Deep vein thrombosis (DVT) is a blood clot that occurs in a deep vein of the body; pulmonary embolism (PE) occurs when a clot breaks free and enters the arteries of the lungs. DVT and PE comprise venous thromboembolism (VTE), an important and growing public health concern. Hospitalization is a major risk factor for VTE, and many VTE events that occur among hospitalized patients can be prevented. A new program of the U.S. Department of Health and Human Services (Partnership for Patients: Better Care, Lower Costs) aims to reduce the number of preventable VTE cases in hospitals. To estimate the number of hospitalizations with VTE each year in the United States, CDC analyzed 2007-2009 data from the National Hospital Discharge Survey (NHDS). The results of that analysis determined that an estimated average of 547,596 hospitalizations with VTE occurred each year among those aged ≥18 years in the United States. DVT was diagnosed in an estimated annual average of 348,558 hospitalizations, and PE was diagnosed in 277,549; both DVT and PE were diagnosed in 78,511 hospitalizations. Estimates of the rates of hospitalizations with VTE were substantially higher among adults aged ≥60 years compared with those aged 18-59 years. These findings underscore the need to promote implementation of evidence-based prevention strategies to reduce the number of preventable cases of VTE among hospitalized patients.     

Moves Afoot To Shore Up Sagging Malpractice Coverage

Abstract

Objective: Venous thromboembolism (VTE) is a common complication in cancer patients. This review summarizes some of the most current knowledge of the epidemiology, risk factors, risk models, prophylaxis, and treatment of VTE in cancer patients. Methods: A literature search was conducted using Pub Med; the search terms were venous thromboembolism, anticoagulation, and cancer. The bibliographies of pertinent studies and review articles were reviewed for additional references. Results: Venous thromboembolism is the second leading cause of death in patients with cancer. Cancer patients with VTE have poorer outcomes compared with noncancer patients with VTE. Many risk factors have been identified for VTE in patients with cancer that are patient-related, cancer-related, or treatment-related. Several biomarkers have been identified as potentially predictive of VTE risk. Risk assessment models such as the Khorana Risk Score stratify cancer patients with low, intermediate, and high risk of developing VTE based on baseline clinical and laboratory variables. Currently, enoxaparin is the preferred anticoagulant for initial VTE treatment in cancer patients. Low molecular weight heparin (LMWH) is recommended for both initial and long-term management of cancer-related VTE. Because the optimal duration of anticoagulation in cancer patients with VTE is unknown, the decision to extend anticoagulation requires weighing the risk of recurrent thrombosis against the risk of major bleeding. Patients with recurrent VTE can be bridged with LMWH, transitioned to full-dose LMWH or treated with LMWH dose escalation. While there is insufficient data to determine whether anticoagulation should be held in the setting of thrombocytopenia, full-dose anticoagulation is typically considered unsafe when platelets are < 50 000/μL. Inferior vena cava filters are currently recommended only for patients with acute VTE and contraindications to anticoagulation. Although management of catheter-associated thrombosis has not been well studied in cancer patients, it is recommended that cancer patients with catheter-associated thrombosis be treated with therapeutic anticoagulation for ≥ 3 months. Venous thromboembolism prophylaxis with UFH, LMWH, or fondaparinux is recommended in all hospitalized nonsurgical cancer patients and cancer patients undergoing major cancer surgery. Primary thromboprophylaxis is only currently recommended in high-risk ambulatory cancer patients such as multiple myeloma patients receiving thalidomide-or lenalidomide- based therapy. Conclusion: Cancer-associated thrombosis is a common problem. As we begin to better understand the risk factors and biomarkers for cancer-associated VTE, we can further refine and develop risk-assessment models to determine those patients who would most likely benefit from anticoagulation. While LMWH products are generally preferred in cancer-related VTE, more research will continue to evolve our understanding of treatment and thrombopprophylaxis in cancer-associated VTE.     

Thromboprophylaxis in pregnant women should be individually tailored

Roeters van Lennep et al. recently evaluated efficacy and safety of thromboprophylaxis with low dose low-molecular-weight heparin (LMWH) in women with intermediate and high risk of pregnancy-related venous thromboembolism (VTE). Lessons to be drawn from this study are that the risk of VTE should be estimated preconceptionally, that the current LMWH prophylaxis is sufficient during pregnancy and the post-partum period for women with an intermediate risk of VTE, that from a haemostatic point of view the post-partum period does not end at 6 weeks but at 3 months, and that the prophylactic LMWH dosage is insufficient in 1 out of 20 women with a high risk of VTE.     

北京某大型综合医院术后静脉血栓栓塞症发生的危险因素分析

目的 探索北京某大型综合医院术后静脉血栓栓塞症(VTE)发生的危险因素,为临床预防和管理术后VTE提供参考依据。方法 检索病案首页数据,查询2012 - 2017年在北京某三甲医院进行外科手术治疗的患者,以出院诊断包含深静脉血栓形成(DVT)或肺血栓栓塞症(PE)的患者作为病例组,对照组采用1∶2匹配方法选择出院诊断无DVT或PE的患者,应用条件logistic回归分析术后VTE发生的危险因素。结果 （1）纳入试验组患者373例,对照组患者710例。高龄、麻醉时间长、术后卧床时间长是术后VTE的独立危险因素（P＜0.05）。（2）术前住院日长、术前采用血栓风险评估、术后采用物理抗凝措施是降低术后VTE风险的因素（P＜0.05）。（3）术后卧床时间对不同性别患者的术后VTE的发生风险影响不同;体腔开放性手术的术后卧床时间对术后VTE发生的OR值为1.24（95%CI:1.12～1.38）,高于腔镜手术（1.14,95%CI:1.09～1.19）。结论 高龄、麻醉时间长、术后卧床时间长的患者发生术后VTE的风险较高,而术前进行血栓风险评估、术后采取物理抗凝措施可以降低术后VTE的发生风险。     

Clinical inquiries. Does anticoagulation prevent thrombosis for persons with fractures distal to the hip?

Low-molecular-weight heparin (LMWH) prophylaxis significantly reduces the total incidence of deep venous thrombosis (DVT) for patients with lower-limb fractures managed with surgical fixation and cast immobilization (strength of recommendation [SOR]: A, based on multiple randomized controlled studies [RCTs]). Evidence is insufficient to show whether LMWH specifically reduces the risk of clinically significant DVTs, and recommendations on its use are conflicting (SOR: C, based on expert opinion). Evidence is insufficient to recommend for or against warfarin prophylaxis for DVT in fractures distal to the hip (SOR: C, based on expert opinion).     

Time trends in incidence rates of venous thromboembolism in a large cohort recruited from the general population

Changes in the incidence of venous thromboembolism (VTE) during the last two decades have not been extensively studied. Therefore, we studied time trends in the incidence rates (IRs) of deep vein thrombosis (DVT) and pulmonary embolism (PE) in a cohort of 26,855 subjects, aged 25–97 years, enrolled in the Tromsø study in 1994/1995. The subject were followed-up throughout 2012, and all symptomatic, objectively confirmed, incident VTEs were identified using multiple sources (hospital discharge-, radiology procedure- and autopsy registry) and validated by review of medical records. Age-adjusted biennial IR per 100,000 person years (PY) with 95% confidence intervals (CI) were calculated using Poisson regression. Between January 1996 and December 2012, 693 VTEs occurred during 368,150 PY of follow up. The IR of VTE increased from 158 (95% CI 116–199) in 1996/1997 to 201 (95% CI 160–243) in 2010/2011. There was a marked increase in the rates of PE (with/without concurrent DVT) ranging from 45 (95% CI 23–67) in 1996/1997 to 113 (95% CI 82–144) in 2010/2011, whereas the rates of isolated DVT decreased (112, 95% CI 77–146 in 1996/1997 and 88, 95% CI 61–115 in 2010/2011). Despite advances in prophylaxis, the IR of VTE has increased slightly during the last 15 years, mainly due to an increase in PE. Although the introduction of better diagnostic tools to some extent may explain the increase in PE rates, our findings suggest that there is still a need for improvement in risk factor management and prevention strategies of first time VTE.     

The creation and implementation of an outpatient pulmonary embolism treatment protocol

The ability to rapidly and accurately risk-stratify patients with venous thromboembolism (VTE), and the availability of direct acting oral anticoagulants have reduced the need for intravenous anticoagulation for patients with deep vein thrombosis (DVT) and pulmonary embolism (PE). Emergency physicians are generally reluctant to discharge patients with VTE without defined and reliable follow up in place, and VTE patients treated with anticoagulants can be at risk for complications related to recurrent VTE and bleeding. In addition, screening for associated diseases (e.g. cancer, hypercoagulable states) may be indicated. Therefore, the outpatient treatment of low risk VTE requires coordinated effort and reliable follow up. By leveraging detailed outcome data and collaborative relationships, we have created a protocol for the safe outpatient treatment of patients with low risk DVT and PE. Our protocol is data driven and designed to address barriers to outpatient VTE management. We expect our protocol to result in improved patient satisfaction, more efficient emergency department (ED) throughput, and decreased cost. Applied nationally, the outpatient treatment of select patients with DVT and PE could have major public health and economic impact.     

Clinical use of parnaparin in major and minor orthopedic sugery: a review

Patients undergoing arthroplasty or other orthopedic surgery show a high risk of venous thromboembolism (VTE), involving mortality, morbidity, and social costs; however, the risk for VTE in minor orthopedic surgery should not be underestimated and antithrombotic prophylaxis may be required. According to the literature, low-molecular-weight heparins (LMWHs) are more effective in preventing VTE than unfractionated heparins (UFHs) or vitamin K antagonists, and have a lower hemorrhagic risk. By comparing different prophylactic regimens, it has been shown that starting the prophylaxis near the time of the operation is the most critical point for efficacy, whether or not the first dose is administered pre- or post-operatively. Moreover, most thromboembolic complications are observed after discharge and, therefore, many clinicians advocate continuing prophylaxis for longer times (6–8 weeks) in order to further reduce the rate for VTE. The literature on parnaparin, a new LMWH, in VTE prophylaxis was reviewed. Parnaparin is equally effective as UFH, but it offers the advantages of a once-daily administration and improved tolerability, thus allowing the home management of patients with no need for laboratory coagulation tests.     

低分子肝素钙预防髋关节置换术后深静脉血栓的疗效观察及护理

目的：探讨低分子肝素钙预防髋关节置换术后深静脉血栓形成（DVT）的护理。方法：术前术后低分子肝素钙5000～6000IU,q12h皮下注射,配合机械方法预防下肢DVT的发生。结果：低分子肝素钙联合机械方法预防DVT效果显著,观察组无1例出现有症状的DVT,与对照组比较有统计学差异,但存在皮下出血、淤血等不良反应。结论：掌握低分子肝素钙使用指征和注射技巧,应用过程中加强观察,可以避免不良反应,同时有效预防DVT的发生。     

D-dimer: establishing a laboratory assay for ruling out venous thrombosis

Patients with venous thrombosis (DVT or PE) have elevated D-dimer, a break-down product of cross-linked fibrin. The determination of D-dimer levels is both a diagnostic and a cost savings tool to rule out VTE. The assay can be used to eliminate those individuals without VTE, but with low or moderate clinical suspicion. The D-dimer assay is inexpensive, automated, has a rapid turnaround time, and uses standard blue-top tubes. After appropriate validation, the assay can be 100 percent sensitive in ruling out DVT or PE, but it will not confirm the presence of VTE as numerous other diseases and procedures can increase levels. The assay should not be used routinely on inpatients or surgery patients. Caution should be used when interpreting results from patients on anticoagulation therapy, since lower D-dimer levels may be found. If properly used, the D-dimer assay can save a healthcare facility significant money by eliminating imaging studies on patients with low or moderate suspicion of DVT or PE.     

Modeling the costs of hospital-acquired infections in New Zealand.

OBJECTIVE: To model the economic costs of hospital-acquired infections (HAIs) in New Zealand, by type of HAI. DESIGN: Monte Carlo simulation model. SETTING: Auckland District Health Board Hospitals (DHBH), the largest publicly funded hospital group in New Zealand supplying secondary and tertiary services. Costs are also estimated for predicted HAIs in admissions to all hospitals in New Zealand. PATIENTS: All adults admitted to general medical and general surgical services. METHOD: Data on the number of cases of HAI were combined with data on the estimated prolongation of hospital stay due to HAI to produce an estimate of the number of bed days attributable to HAI. A cost per bed day value was applied to provide an estimate of the economic cost. Costs were estimated for predicted infections of the urinary tract, surgical wounds, the lower and upper respiratory tracts, the bloodstream, and other sites, and for cases of multiple sites of infection. Sensitivity analyses were undertaken for input variables. RESULTS: The estimated costs of predicted HAIs in medical and surgical admissions to Auckland DHBH were dollar 10.12 (US dollar 4.56) million and dollar 8.64 (US dollar 3.90) million, respectively. They were dollar 51.35 (US dollar 23.16) million and dollar 85.26 (US dollar 38.47) million, respectively, for medical and surgical admissions to all hospitals in New Zealand. CONCLUSIONS: The method used produces results that are less precise than those of a specifically designed study using primary data collection, but has been applied at a lower cost The estimated cost of HAIs is substantial but only a proportion of infections can be avoided. Further work is required to identify the most cost-effective strategies for the prevention of HAI.     

Economic burden of hospital admissions for patients with acute bacterial skin and skin structure infections in the United States

ABSTRACT

Objectives: We estimated the total US hospital costs associated with acute bacterial skin and skin structure infection (ABSSSI) admissions as well as the admissions that may have been potential candidates for outpatient parenteral antimicrobial therapy (OPAT).

Methods: We assessed inpatient admissions for ABSSSI from the Premier database (2011–2014), focusing on all admissions of adults with length of stay (LOS) ≥ 1 days and a primary diagnosis of erysipelas, cellulitis/abscess, or wound infection. We performed a detailed analysis of 2014 admissions for patient, treatment, hospital, and economic characteristic variables. Using published selection criteria, we identified a subset of patients admitted in 2014 who may have been potential candidates for OPAT.

Results: We analyzed 277,971 admissions. In 2014, most admissions were for cellulitis without major complications or comorbidities; mean ± SD LOS was 4.0 ± 3.0 days, and total hospital cost per admission was $6400 ± $6874, 54% of which was attributable to room costs. Among 2014 admissions, 14% involved patients with clinical characteristics suggesting that they were consistent with guideline recommendations for exclusive treatment with OPAT. Compared with all admissions in the year, these admissions were of younger patients (aged 50 vs. 55 years), admitted more frequently for cellulitis (90% vs. 70%), with shorter LOS (2.8 ± 1.8 days), and lower mean total hospital cost per admission ($4080 ± $3066).

Conclusions: Admissions for ABSSSI impose a substantial cost to US hospitals, with half of costs attributable to room costs. When extrapolated to all US patients admitted to the hospital for ABSSSI during 2014, had OPAT guidelines been universally followed, admissions may have been reduced by 14%, thereby saving US hospitals $161 million.     

Utilization of Parenteral Anticoagulants and Warfarin: Impact on the Risk of Venous Thromboembolism Recurrence in the Outpatient Setting

Background

Clinical guidelines recommend parenteral anticoagulation therapy with an early initiation of warfarin therapy for the treatment of patients with acute venous thromboembolism (VTE) and the prevention of recurrence.

Objectives

To evaluate the outpatient utilization of parenteral anticoagulant therapy and warfarin among patients with VTE, and to examine the effects of parenteral anticoagulant use and the time to warfarin initiation from VTE diagnosis on the risk for VTE recurrence.

Methods

The Truven Health MarketScan Commercial Claims Database was used to identify patients aged 18 to 64 years who had an outpatient claim for deep-vein thrombosis or pulmonary embolism between January 2010 and December 2011 (ie, index date) and had no VTE diagnosis or treatment during the 12 months before the index date, had no hospital or emergency department VTE claim within 7 days after the index outpatient VTE claim, and had received warfarin <30 days after the index date. A recurrent VTE event was defined as a VTE-related emergency department visit or hospitalization within 8 to 365 days after the index date. A Cox proportional hazards model was used to estimate the adjusted hazard ratio (HR) associated with VTE recurrence risk related to parenteral anticoagulant use and warfarin initiation timing.

Results

A total of 5820 patients were included in the study (mean age, 50.5 years); of these, 45% were female. A total of 75.7% (4403) of the patients receiving warfarin also received a parenteral anticoagulant, and the median time from VTE diagnosis to warfarin initiation was 5 days for parenteral anticoagulant users compared with 11 days for nonusers. Parenteral anticoagulant use was associated with a 49% recurrent VTE risk reduction (HR, 0.51; 95% confidence interval [CI], 0.43–0.60; P <.001). Each day of delayed warfarin initiation from the diagnosis of acute VTE was associated with a 1% increase in the risk for VTE recurrence (HR, 1.01; 95% CI, 1.01–1.02; P = .003).

Conclusions

Overall, 1 in 4 patients with VTE who had received warfarin in the outpatient setting did not receive parenteral anticoagulation therapy. Among those who received warfarin, its initiation was not always timely, despite its positive effects on reducing VTE recurrence. These findings highlight the potential quality-of-care concerns associated with the failure to use or the delayed implementation of guideline-recommended VTE treatment, and the need to improve compliance with clinical guidelines in the treatment of patients with VTE.Venous thromboembolism (VTE) encompasses deep-vein thrombosis (DVT) and pulmonary embolism (PE). VTE is a chronic disease that is associated with a high risk for recurrence, especially during the initial months of therapy.1–7 The risk for VTE recurrence is higher for patients with “unprovoked” VTE (ie, VTE occurring in the absence of malignancy or any of the factors of “provoked” VTE) than for patients with provoked VTE (ie, VTE occurring within 3 months of hospitalization, major surgery, pregnancy, trauma, or fracture).8 The rates of VTE recurrence in patients with unprovoked VTE have been estimated at 10% after 1 year and 30% after 5 years of the first VTE event compared with patients with VTE provoked by surgery, in whom the recurrence rates are estimated to be 1% after 1 year and 3% after 5 years.8VTE recurrence is recognized as an important risk factor for mortality and long-term complications, such as postthrombotic syndrome after DVT and pulmonary hypertension after PE. Recurrent VTE events also pose a significant economic burden to the healthcare system. In a recent retrospective analysis of claims data, patients with VTE recurrence were found to have 2.2-fold to 3-fold higher healthcare costs in the 1 year after their first VTE event, which was primarily driven by an increase in inpatient services utilization.7The American College of Chest Physicians (ACCP) recommends initial parenteral anticoagulant therapy as an option for the initial treatment of acute DVT or PE.8 The ACCP guidelines recommend the early initiation of warfarin therapy rather than delayed initiation (eg, on the same day as parenteral therapy is started), and the continuation of parenteral anticoagulation therapy for a minimum of 5 days until the international normalized ratio (INR) is ≥2.0 for at least 24 hours. The ACCP also recommends continuation of anticoagulation therapy for 3 months in patients with acute DVT and PE to allow for the complete treatment of the acute episode of VTE and to prevent recurrent episodes of VTE.8The outpatient treatment of uncomplicated VTE has become more common since the availability of subcutaneous low-molecular-weight heparin (LMWH) therapy as an alternative to intravenous unfractionated heparin for the treatment of VTE.8–10 Although the administration of heparin therapy and INR monitoring are much easier in the inpatient setting, there are challenges associated with the outpatient treatment of VTE. The outpatient use of LMWH requires the coordination of care, laboratory monitoring, and patient education and participation in treatment.11It remains unclear how well parenteral anticoagulation therapy utilization in the outpatient clinical practice is consistent with the treatment guidelines for VTE. In addition, although previous randomized clinical trials suggest that the early initiation of warfarin therapy with a shorter course of heparin therapy for approximately 5 days is as effective as the delayed initiation of warfarin with a 10-day course of heparin, and that this approach has the benefit of reducing the risk for heparin-induced thrombocytopenia,8 it remains unclear how well this recommendation has been adopted in real-world clinical settings.The objectives of this study were to assess the utilization of parenteral anticoagulation therapy and the timing of the initiation of warfarin for the treatment of VTE in the outpatient setting, and to examine the effects of parenteral anticoagulation therapy and the timing of warfarin initiation relative to a diagnosis of VTE on the risk of VTE recurrence.

KEY POINTS

• ▸ Recurrent venous thromboembolism (VTE) is a risk factor for mortality and long-term, serious complications; the risk for recurrence is especially high in the early months of an acute VTE event.
• ▸ Recurrent VTE poses a significant economic burden to the healthcare system.
• ▸ Current clinical guidelines recommend the early addition of warfarin to parenteral anticoagulation to reduce the risk for VTE recurrence.
• ▸ In this study of 4403 patients with acute VTE who received parenteral anticoagulants in the outpatient setting, only 25% of patients received warfarin on the same day of initiating parenteral anticoagulant therapy; 52% received warfarin 3 days after initiating parenteral anticoagulant therapy.
• ▸ Overall, parenteral anticoagulation plus warfarin reduced the risk for recurrent VTE by 49% over 1 year.
• ▸ In this study, each day that the initiation of warfarin was delayed from the VTE diagnosis translated to a 1% increase in VTE recurrence risk.