Recurrent Venous Thromboembolism Events Research Articles

Cancer-associated unsuspected pulmonary embolism

Clinically unsuspected pulmonary embolism (UPE) is frequently diagnosed in cancer patients undergoing routine computed tomography scans for staging purposes or treatment response evaluation. The reported incidence of UPE ranges from 1% to 5% which probably represents an underestimation. A significant proportion of cancer patients with UPE actually do have pulmonary embolism (PE) related symptoms. However, these can erroneously be attributed to the cancer itself or to cancer therapy leading to a delayed or missed diagnosis. The incidence of UPE is likely to increase further with the improvements of imaging techniques. Radiologic features of UPE appear similar to symptomatic PE with nearly half of the UPE located in central pulmonary arteries and one third involving both lungs. UPE in cancer patients is not a benign condition with rates of recurrent venous thromboembolic events, bleeding and a mortality rate comparable to cancer patients with symptomatic PE. Current guidelines suggest that UPE should receive similar initial and long-term anticoagulant treatment as for symptomatic PE. However, direct evidence regarding the treatment of UPE is scarce and treatment indications are largely derived from studies performed in cancer patients with symptomatic venous thromboembolism. Selected subgroups of cancer patients with UPE such as those with sub-segmental UPE may be treated conservatively by withholding anticoagulation and avoiding the associated bleeding risk, although this requires further evaluation.

Cost-Effectiveness Analysis of Extended Duration Anticoagulation with Rivaroxaban to Prevent Recurrent Venous Thromboembolism

Extended duration anticoagulation with rivaroxaban for an additional 6-12 months can reduce recurrent venous thromboembolic events (VTE) compared to placebo by ~82%, but at the detriment of increased bleeding. We sought to estimate the cost-effectiveness of extended duration prophylaxis of recurrent VTE with rivaroxaban. A Markov model was developed to estimate the cost-effectiveness of extended duration rivaroxaban, 20mg daily, compared to placebo using a Medicare perspective, a one-monthcycle length and a 40-year time horizon. The model assumed a cohort of 58-year-old patients who had already completed an initial 6-12 months of anticoagulation with rivaroxaban or a vitamin K antagonist; and whom prescribers had clinical equipoise with respect to the need for continued anticoagulation. Data sources included EINSTEIN-Extension and other published studies of VTE. Outcomes included direct treatment costs (in 2013US$), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Extended duration rivaroxaban resulted in higher treatment costs ($22,645 vs. $22,083) but yielded greater QALYs (16.167 vs. 16.134) as compared to placebo; corresponding to an ICER of $17,030/QALY gained. Our model was most sensitive to the baseline risk of bleeding and recurrent VTE, the hazard ratio of developing a recurrent event while on rivaroxaban and time horizon. Monte Carlo Simulation suggested rivaroxaban would be cost-effective in 66% of 10,000 iterations, assuming a willingness-to-pay threshold of $50,000/QALY. Despite the cost of rivaroxaban and an increased risk of bleeding, extending VTE treatment for an additional 6-12 months with rivaroxaban was found cost-effective compared to the placebo over a 40-year time horizon.

A systematic review of the utility of residual vein obstruction studies in primary and secondary venous thrombosis.

Background. Residual vein obstruction (RVO), the persistence of venous thrombosis with time and often after anticoagulation, may indicate a systemic prothrombotic condition. Prior studies have shown varying efficacy in using RVO as a risk factor for future venous thromboembolic (VTE) recurrence. Methods. To assess whether positive RVO imaging predicts recurrent VTE events, we performed a meta-analysis on studies in which patients with documented VTEs, anticoagulated for a minimum of 4 weeks, had repeat sonography to assess RVO and were subsequently followed for recurrent events. Results. Thirteen studies met inclusion criteria: 3531 patient VTE events with 3474 evaluable results were analyzed. The presence of RVO was associated with recurrence in all VTE (OR 1.93; 95% CI: 1.29, 2.89) and secondary VTE (OR 2.78; 95% CI: 1.41, 5.5) but not for primary VTE (OR 1.35; 95% CI: 0.87, 2.08). When cancer patients were eliminated from the secondary VTE group, there was no longer a significant association of RVO with VTE recurrence (OR 1.73; 95% CI: 0.81, 3.67) while in the subset of cancer patients, presence of RVO was associated with an increase in VTE recurrence risk (OR 5.14; 95% CI: 1.59, 16.65, P < 0.006). Conclusions. We conclude that the presence of RVO is associated with recurrence in secondary VTE but not in primary VTE and that association may be driven by the subset with cancer.

Impact of chronic kidney disease on the risk of clinical outcomes in patients with cancer‐associated venous thromboembolism during anticoagulant treatment

Information on recurrent venous thromboembolic events (VTEs) and major bleeding risks during anticoagulant treatment in patients with cancer-associated VTEs and chronic kidney disease (CKD) is scarce, although it is of relevance in establishing better tailored management strategies in these patients. We compared risks of recurrent VTEs and major bleeds in cancer-associated VTE patients with and without CKD. A total of 1684 patients diagnosed with a cancer-associated VTE between 2001 and 2011 were followed for 180days after VTE diagnosis. Patients were treated mainly with low-molecular-weight heparin (LMWH) or vitamin-K antagonists (VKA). Primary outcomes were recurrent VTE and major bleeding. Secondary outcome was fatal bleeding. Recurrent VTEs occurred in 15.9/100 patient years (py) in patients without CKD (eGFR>60mL min(-1) ), 19.5/100py in those with CKD stage 3A (eGFR 45-60mL min(-1) ), 14.9/100py in those with CKD 3B (eGFR 30-45mL min(-1) ), and 6.8/100py in patients with CKD 4-5 (eGFR<30mL min(-1) ). Major bleeding occurred in 11.4/100 py in patients without CKD, 18.5/100 py in those with CKD stage 3A, 16.0/100 py in those with CKD 3B, and 40.8/100 py in patients with CKD 4-5. Fatal bleeding occurred in 1.1/100 py, 3.4/100 py, 6.3/100 py and 15.7/100 py, respectively. These increased bleeding risks in CKD patients were mainly observed in those on LMWH treatment, not VKA. The risk of major bleeding was increased in CKD patients with VTE and cancer, and was most prominent in those treated with LMWH and an eGFR<30mL min(-1) . These results indicate that LMWH should be used with caution in this specific population.

High prevalence of recurrent thrombosis in subsets of cancer patients with isolated gonadal vein thrombosis: A single center retrospective study

Cancer patients are a high-risk population for venous thromboembolism (VTE); the natural history of gonadal vein thrombosis (GVT) occurring in cancer patients is not well described in the medical literature. Utilizing a software program the computerized tomographic scan reports of patients at a single cancer center from January 1, 2004 to June 30, 2011 were searched for the term GVT. Patients included in this analysis had a diagnosis of cancer, an isolated GVT (i.e. no evidence of thrombosis at another site), no symptoms referable to the GVT, and at least six months of follow-up information. All subsequent recurrent VTE events were confirmed by imaging studies. 196 cancer patients with GVT were identified. The majority of patients in this analysis had metastatic disease (118, 61.2%) as well as active cancer (167, 85.2%). Twenty patients (10.8%) developed recurrent VTE (median follow-up 14.5 months); median time to recurrent VTEs was 5.5 months (range 0-19 months). When considering only patients with without a recent history of gynecologic surgery, VTE recurrence rates were 14.3%. Active cancer was the only risk factor significantly associated with recurrent VTE (P=0.047). Based upon the patient's risk factors for VTE, treatment of an incidentally detected GVT in cancer patients with anticoagulation, as per guidelines for other VTE sites, may be indicated in certain high risk subgroups, especially those patients with active cancer who have not had prior pelvic surgery.

Cost-effectiveness of additional catheter-directed thrombolysis for deep vein thrombosis

Additional treatment with catheter-directed thrombolysis (CDT) has recently been shown to reduce post-thrombotic syndrome (PTS). To estimate the cost effectiveness of additional CDT compared with standard treatment alone. Using a Markov decision model, we compared the two treatment strategies in patients with a high proximal deep vein thrombosis (DVT) and a low risk of bleeding. The model captured the development of PTS, recurrent venous thromboembolism and treatment-related adverse events within a lifetime horizon and the perspective of a third-party payer. Uncertainty was assessed with one-way and probabilistic sensitivity analyzes. Model inputs from the CaVenT study included PTS development, major bleeding from CDT and utilities for post DVT states including PTS. The remaining clinical inputs were obtained from the literature. Costs obtained from the CaVenT study, hospital accounts and the literature are expressed in US dollars ($); effects in quality adjusted life years (QALY). In base case analyzes, additional CDT accumulated 32.31 QALYs compared with 31.68 QALYs after standard treatment alone. Direct medical costs were $64,709 for additional CDT and $51,866 for standard treatment. The incremental cost-effectiveness ratio (ICER) was $20,429/QALY gained. One-way sensitivity analysis showed model sensitivity to the clinical efficacy of both strategies, but the ICER remained < $55,000/QALY over the full range of all parameters. The probability that CDT is cost effective was 82% at a willingness to pay threshold of $50,000/QALY gained. Additional CDT is likely to be a cost-effective alternative to the standard treatment for patients with a high proximal DVT and a low risk of bleeding.

One-year adherence to warfarin treatment for venous thromboembolism in high-risk patients and its association with long-term risk of recurrent events.

Warfarin is the predominant oral anticoagulant used for the prevention of recurrent venous thromboembolism (VTE) events. However, its long-term use is complicated by the need to manage the drug within a narrow therapeutic range and by possible food and drug interactions. To examine the association between 1-year adherence, measured through compliance with and persistence on warfarin treatment for VTE, and long-term risk of recurrent events among patients at high risk. Medical and pharmacy claims for patients with commercial or Medicare supplemental insurance in the Thomson Reuters MarketScan database were analyzed. Adult patients with medical claims with an associated VTE diagnosis between January 1, 2006, and March 31, 2008, were identified. The index date was defined as the date of the first observed VTE claim or the date of discharge if the index event was a hospital stay. High-risk patients (patients with cancer, or noncancer patients who did not have reversible risk factors during the 3-month period prior to the index date) who filled a warfarin prescription within 2 weeks of the index date were included. Persistence was evaluated in terms of discontinuation, defined as a 90-day gap in warfarin supply during a 1-year assessment period following the index date. Compliance was measured by the proportion of days covered (PDC) over the 1-year assessment period, with PDC less than 0.8 defined as noncompliance. Recurrent VTE events were identified as hospitalizations where VTE was the primary diagnosis after the 1-year assessment period and until patients were lost to follow-up. The association between adherence to warfarin therapy and VTE recurrence was evaluated descriptively via Kaplan-Meier curves and a Cox proportional hazards model, adjusted for patient demographic and clinical characteristics. A similar analysis using the medication possession ratio (MPR) as a measure of compliance was also performed in a subset of patients who had filled at least 2 warfarin prescriptions. The study included 8,040 VTE patients identified as being at high risk of recurrence (mean age 61 years, 59.4% male), of whom 76.9% were not compliant with warfarin therapy based on PDC, and 51.5% discontinued therapy. Among those with at least 2 warfarin prescriptions (n = 7612), 34.1% of high-risk patients were not compliant with warfarin therapy between the first and last refills based on MPR. Kaplan-Meier curves showed that patients who were compliant or continued warfarin therapy were less likely to experience a VTE event (all P less than 0.05). Noncompliant patients had a 3 times greater risk of VTE recurrence than compliant patients, based on PDC (hazard ratio [HR] = 3.01, 95% confidence interval [CI]: 1.28-4.97). Among the subpopulation who filled at least 2 warfarin prescriptions, noncompliant patients (based on MPR) were also found to be more likely to have recurrent VTE events, compared with compliant patients (HR = 1.60, 95% CI: 1.18-2.16). Patients who discontinued warfarin were more likely to have recurrent VTE events compared with patients who did not discontinue on warfarin treatment (HR = 1.48, 95% CI: 1.09-2.01). Adherence to a year of therapy was low in patients at high risk of recurrent VTE, even though long-term therapy should be considered in this population. Noncompliance and discontinuation of warfarin treatment over a 1-year period was associated with a higher risk of recurrent VTE. Future research should investigate and differentiate between patient and provider discontinuation to develop strategies to improve compliance and persistence with appropriate anticoagulation therapy that may potentially reduce recurrent VTE.

Abstract 52: Association of Heparin Lead-in Therapy and Recurrence in the Treatment of Venous Thromboembolism

Background: Venous thromboembolism (VTE) encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE). Anticoagulant treatment significantly decreases the risk of recurrent VTE events and is typically initiated with the administration of a heparin therapy along with warfarin followed by warfarin treatment alone. The objective of this study was to assess the association between heparin lead-in therapy and VTE recurrence in patients receiving warfarin. Methods: Data from adult patients who had a VTE diagnosis in a large claims database (period 2005 - 2011), a warfarin claim within 30 days and continuous eligibility for at least 12 months pre/post first (index) diagnosis, were analyzed. Patients with atrial fibrillation, VTE, or treatment with warfarin therapy prior to the index date were excluded. Patients were classified into 4 cohorts: 1) Outpatient DVT; 2) Outpatient PE; 3) Inpatient DVT; 4) Inpatient PE. Inpatient cohort patients had an index inpatient VTE claim or had an inpatient VTE claim within 7 days of an index outpatient VTE claim. Outpatient cohort patients were required to have another outpatient VTE claim within 7 days of their index claim. Patients with both DVT and PE claims were included in the PE cohorts. Recurrent VTE was defined as the presence of an inpatient VTE claim within 365 days from the index date. Heparin use was identified by a UFH/LMWH pharmacy claim within 7 days of the outpatient index date or discharge from an inpatient VTE index event. Cox proportional hazard models adjusting for age, gender, health insurance type and baseline Elixhauser comorbidities were used. Results: A total of 39,424 patients met study criteria. Mean (SD) age was 59.8 (15.6) years and 50.6% (19,946/39,424) were female. Most patients (72.0%; 28,388/39,424) had an index inpatient event with a mean (SD) LOS=5.4 (4.1) days. Outpatient DVT/PE patients who used heparin had significantly lower rates of VTE recurrence vs. those who did not ( P &lt;0.05). Post-discharge heparin use was not associated with VTE recurrence rates within inpatient cohorts. Conclusion: The use of heparin lead-in therapy can significantly reduce VTE recurrence in the Outpatient VTE cohorts. Due to the lack of inpatient drug use data to identify heparin use in this claims database, additional studies are needed to confirm our Inpatient cohort results.

Clinical Predictors of Confirmed Venous Thromboembolism in Patients with a Suspected Recurrent Venous Thromboembolism: A Retrospective Study of the Reverse I Cohort

AbstractAbstract 1153 Background:Many clinical decision rules (CDR), such as the Wells models for deep vein thrombosis of the legs (DVT) and pulmonary embolism (PE), have been established for patients with suspected first venous thromboembolism (VTE). However these rules may have limitations for patients with suspected recurrent VTE. First, patients with suspected PE and a history of VTE have their diagnosis more likely confirmed than patients with a suspected PE without a history of VTE (40.3 vs. 20.6%) (Le Gal G et al. Arch Intern Med, 2006), suggesting a different pre-test probability. Furthermore, patients who had a previous pulmonary embolism often have complaints of chronic dyspnea (Klok FA et al. Eur J Intern Med, 2008), which could complicate the risk estimation of recurrent PE. A similar scenario arises for patients who suffered a DVT, as 30–50% of patients will show signs and symptoms of post-thrombotic syndrome (PTS) following a deep vein thrombosis (Kahn SR. Curr Opin Pulm Med, 2006). In addition, the value of D-dimer testing is still uncertain in patients with suspected recurrent VTE. Finally, imaging has limitations, as residual thrombosis may be present and may be misdiagnosed as an acute recurrent event. Hence, because pre-test probability, laboratory testing and diagnostic imaging performances differ in patients with a suspected recurrent VTE, a different approach may be needed for effective management of these patients.Our objective was to study clinical predictors for the diagnosis of recurrent VTE in patients with a history of VTE. Methods:The REVERSE I study enrolled patients with a first unprovoked, objectively proven VTE (Rodger M et al. CMAJ, 2008). Each patient in the REVERSE I cohort that had a suspected recurrent VTE during follow-up was screened for eligibility. Only first adjudicated suspected recurrent events were studied. All these events were blindly adjudicated by an independent committee. Potential clinical predictors of recurrent VTE consisted of clinical predictors collected at the baseline visit (5–7 months after the unprovoked event), and of information collected in physicians’ clinical notes, laboratory or imaging results at the time of the suspected recurrent VTE.The predictive value of each predictor was determined by the Chi-square test for nominal data and the unpaired 2-tailed T-test for continuous data. Results:In the REVERSE I cohort, out of the 646 patients who were followed, 402 patients had a suspected recurrent VTE within a mean of 20.2 months (range: 0 – 97 months) of follow-up. After screening, 376 patients were enrolled in our study: 52.7 % of patients were males, and the mean age was 53.1 years (± 17.5). Among all suspected recurrent VTE events, male gender and a positive d-dimer result at the time of suspected recurrent VTE (p < 0.01), as well as symptoms occurring for 10 days or less at the time of presentation (p < 0.05) were in favor of a recurrent VTE diagnosis. In addition, mean age was higher in patients with a confirmed recurrent VTE (p < 0.05).In patients with suspected DVT, the presence of leg swelling was in favor of a confirmed diagnosis (p < 0.01), while leg pain was not associated with a higher rate of confirmed DVT. A suspected DVT in the same leg as the previous event seemed less likely to have a confirmed diagnosis of recurrent DVT. However this trend was not statistically significant.In patients with suspected PE, mean oxygen saturation was lower among patients with a new PE diagnosis (p < 0.05). Chest pain and shortness of breath were not important predictors.Finally, in the case of a suspected DVT and PE event, shortness of breath was a significant predictor (p < 0.05) for the diagnosis of recurrent VTE. Conclusion:This is the first study to show that predictors for the diagnosis of a recurrent VTE may be different than predictors for the diagnosis of a first VTE. For instance, our results show that male gender is not only a risk factor for recurrent VTE (McRae S et al. Lancet, 2006), but is also an important predictor for confirmed VTE among patients with suspected recurrent VTE, while none of the existing CDRs take this in consideration. A CDR specific to patients with a history of VTE may be needed for better management of these patients. Disclosures:Le Gal:Bayer, bioMérieux, GSK, Leo Pharma, Sanofi Aventis: Honoraria.

Outcome of incidentally diagnosed pulmonary embolism in patients with malignancy

With improvements in the quality of computed tomography (CT) examinations, pulmonary embolism is increasingly being detected incidentally in oncology patients undergoing routine cancer staging CT scans. The purpose of this review is to update current evidence on the prognosis of cancer patients diagnosed with incidental pulmonary embolism. Several recent observational studies have shed some light on the prognostic implications of diagnosing incidental pulmonary embolism in cancer patients. In general, anticoagulant treatment is initiated in these patients. Even during treatment, recurrent venous thromboembolic events may occur with a frequency that is comparable to cancer patients who have symptomatic pulmonary embolism. It has been demonstrated that the diagnosis of incidental pulmonary embolism is associated with adverse survival in cancer patients, and the long-term mortality rate in incidental pulmonary embolism patients seems to approach that of symptomatic pulmonary embolism patients. Overall, the body of literature on patients with incidental pulmonary embolism is sparse and does not allow firm recommendations on the therapeutic approach to these patients. Yet, in the absence of data on the natural clinical course of these patients, and the presence of cohort studies suggesting that incidental pulmonary embolism may impact recurrent venous thromboembolism and mortality, current consensus is to treat these patients in the same manner as symptomatic patients.

Desfechos clínicos após investigação para Embolia Pulmonar utilizando TC de tórax/membros inferiores

The diagnosis of pulmonary embolism (PE) still requires long work-up periods and multiple tests. We aim to assess clinical outcomes after a negative investigation using a combined protocol of CT pulmonary angiography and CT venography (CTA/CTV) as a sole diagnostic test in unselected patients with suspected PE. This retrospective cohort study enrolled consecutive patients with suspected PE who were investigated with a combined CTA/CTV protocol. Patients who had an initially negative investigation and were not anticoagulated were followed for 6 months for the occurrence of recurrent venous thromboembolic events. Out of 425 patients with suspected PE, 62 (14.6%) had venous thromboembolism diagnosed on the initial CTA/CTV. The mean age was 56 ± 19 years and 61% of the population fell into the low clinical probability category. Isolated deep vein thrombosis represented 21% of all venous thromboembolic events, and when considering the whole population, CTV was associated with an increment in diagnostic yield of 3.1%. Our cohort was composed of 320 patients with initially negative CTA/CTVs and who were not anticoagulated. After 6 months of follow up, only three patients presented with recurrent thromboembolic events (0.9%; 95% CI -0.1% - 2.0%) and none was fatal. There were no PE-related deaths. Our study suggests that a diagnostic strategy that utilizes CTA/CTV as a sole diagnostic test can safely rule out PE in a low to moderate risk population and is associated with favorable outcomes with a negative predictive value of 99.1%.

Regulatory, policy and quality update for venous thromboembolism and stroke in United States hospitals

Stroke and venous thromboembolism (VTE) have a large impact on the United States (US) healthcare system. It is estimated that up to 1.7million new and recurrent stroke and VTE events are occurring in the US on an annual basis with the combined cost approaching over $200billion per year. A significant amount of stroke and VTE are preventable from appropriate antithrombotic use in at-risk patients and the Center for Medicaid and Medicare Services, the Joint Commission, the National Quality Forum and other key quality and regulatory entities have prioritized minimizing the impact of morbidity, mortality and avoidable costs related to these diseases. This review provides a brief history, overview, and update for the development of quality measures, quality systems, and regulatory and policy changes as related to stroke and VTE within the US healthcare system.

Safety of low-molecular-weight heparin during pregnancy: a retrospective controlled cohort study

To study the safety of low-molecular-weight heparin (LMWH) treatment during pregnancy for the mother and the foetus. Retrospective controlled cohort study. Six hundred and forty-eight pregnancies exposed to LMWH were compared with 626 unexposed pregnancies. Principal characteristics, indications for LMWH use, and maternal and foetal complications were reported for each pregnancy. Data were obtained from patients' electronic hospital records and analysed using Statistical Package for the Social Sciences Version 17.0. The incidence rates of various pregnancy complications did not differ between the groups (LMWH group vs control group): 1.56% vs 1.1% for thrombocytopenia, 8.7% vs 6.5% for preterm delivery, 0.7% vs 0.3% for stillbirth, 1.4% vs 1.0% for severe pre-eclampsia, 2.7% vs 2.2% for foetal growth restriction, and 10.7% vs 7.8% for antenatal bleeding. One serious antenatal maternal haemorrhage occurred in the LMWH group (0.15%), but this was unrelated to LMWH use. The caesarean section rate and the amount of bleeding during delivery were similar in the two groups (21% vs 19% and 500 vs 450 ml, respectively). The risk of major blood loss during labour (>1000 ml) was no higher in the LMWH group compared with the control group. The incidence of allergic skin reactions was 0.3% in the LMWH group. No heparin-induced thrombocytopenia or symptomatic osteoporotic fractures were observed. Recurrent venous thromboembolic events occurred in 2.5% of patients in the LMWH group. This study indicates that the use of LMWH is safe during pregnancy.

Incidence and characterization of venous thromboembolic events (VTE) in patients with pancreatic cancer: Effect of timing of VTE on survival.

4037 Background: Patients (pts) with pancreatic cancer are at high risk for VTE, and the occurrence of VTE can affect pts’ prognosis. The purpose of this study was to evaluate the incidence of VTE and the impact of timing of VTE (early vs. late) on survival. Methods: Medical record of 260 pts with pancreatic cancer, newly referred to UT MDACC during one year period from 1/1/2006 to 12/31/2006, were reviewed for the incidence of VTE during a 2-year follow-up period from the date of diagnosis. All VTE episodes were confirmed by radiologic studies. Survival analysis was conducted using Kaplan-Meier analysis and Cox proportional hazard models. Results: Of the 260 pts, 47 pts (18%) had 51 episodes of VTE during the 2-year follow-up. The median age of the pts with VTE was 61 years (range: 28-86) and 53% were males. Of the 47 pts with VTE, 27 (57%) had PE, 19 (40%) had DVT and 1 had concurrent PE/DVT. Three pts had recurrent VTE during the study period. Median follow-up time for OS was 192 days (range: 1-1652 days). Kaplan-Meier Survival analysis showed that those who developed VTE earlier (within 30 or 90 days) had shorter median overall survival (OS) compared with those who had VTE beyond these time points. The hazard ratios, 95% CI, and median OS at 1 year are summarized in the table below. Conclusions: The incidence of VTE is high in pts with pancreatic cancer. The timing of VTE had a significant impact on OS; pts who had an early development of VTE had a shorter overall survival. [Table: see text]

Prevalence of recurrent thrombosis in cancer patients with isolated gonadal vein thrombosis: A retrospective study.

e19645 Background: The natural history of isolated gonadal vein thrombosis (GVT) occurring in cancer patients (pts) is not well described in the medical literature. GVT in cancer pts it is of uncertain clinical significance. Methods: Utilizing a software program allowing a searchable database of radiology reports, the computerized tomographic scan (CT) reports of pts at a single cancer center from January 1, 2004 to June 30, 2011, were searched for the term “gonadal vein thrombus”. Pts included in this analysis had a diagnosis of cancer, isolated GVT (i.e. no evidence of thrombosis at another site), and at least six months of follow-up information. Results: 162 cancer pts with GVT were identified for analysis [median age 57.8 ± 12 years, right GVT 89 pts (54.9%), left GVT 59 pts (36.4%), bilateral 14 pts (8.6%)]; the majority of the pts (96, 59.3%) had a non-gynecologic malignancy. At the time of diagnosis of GVT the majority of pts were receiving chemotherapy (84, 51.9%); 70 pts (43.2%) had surgery within the prior six months (the most common being hysterectomy, 127 pts, 78.6%). The majority of pts in this study had metastatic disease (93, 57.4%) as well as active cancer (138, 85.1%, defined as GVT occurring at the time of cancer diagnosis, disease recurrence, metastatic disease, or treatment for cancer within the prior six months); median follow-up time was 22 months. A minority of pts received anticoagulation (28pts, 17.2%). Twenty-two pts (13.6%) developed a recurrent venous thromboembolic event (VTE); these events were pulmonary embolism (12 pts, 7.4%), deep venous thrombosis (5 pts, 3.1%), inferior vena cava thrombosis (4 pts, 2.5%). Median time to development of re-thrombosis was 7 months (range 2-13.5 months). Active cancer was the only risk factor significantly associated with recurrent VTE (p = 0.047); pts with prior hysterectomy had a significantly reduced risk of recurrent VTE (p = 0.036). Conclusions: Incidental isolated GVT identified in cancer pts has a high risk of recurrent VTE (13.6%). Based upon specific pts risk factors for VTE, treatment of an incidentally detected GVT in cancer pts with anticoagulation, as per guidelines for other VTE sites, may be indicated.

CATCH: A randomized trial comparing tinzaparin versus warfarin for treatment of acute venous thromboembolism (VTE) in cancer patients.

TPS9149^ Background: VTE is a major cause of morbidity and mortality in cancer patients. LMWHs have been shown to be superior to warfarin in one randomized study, but adequately powered confirmatory studies have not been conducted and warfarin continues to be widely used for treatment of cancer-associated VTE. Methods: We are conducting an open-label, randomized trial of tinzaparin versus warfarin in 900 patients with active cancer and symptomatic proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Tinzaparin is given at full treatment doses (175 IU/kg once daily) for 6 months in the experimental arm and initial tinzaparin treatment for 5-10 days followed by dose-adjusted warfarin (target INR 2.0-3.0) is given for 6 months in the control arm. The primary composite outcome is time to recurrent VTE event, including incidentally diagnosed VTE and fatal PE. Baseline characteristics will be analysed for their ability to predict the risk for recurrent VTE or bleeding. In particular, the parameters of the Khorana scale and Wells rule will be tested for their usefulness in predicting recurrent VTE. Predictive biomarkers will be tested including D-dimer and Tissue Factor. Assessment of post-thrombotic syndrome (PTS), quality of life and healthcare resource utilization will also be performed. The trial is recruiting in &gt; 160 sites in &gt;25 countries in 4 continents (NCT01130025). As of Jan 2012, 135 sites were activated for study enrolment and 228 patients have been enrolled. We anticipate completion of enrolment in Jan 2013. The results obtained from this study will add significantly to the knowledge on the efficacy, safety and cost-effectiveness of LMWH to prevent recurrent VTE. Important prospective data on the clinical significance of incidental VTE in patients with active cancer will be generated, and analyses of risk stratification parameters will add important information that may help to further tailor therapy. The study of PTS, which has not previously been done in this selected patient population, will add to the evidence that tinzaparin significantly reduces the incidence of PTS and leg ulcers (Hull et al, Am J Med 2009;122:762-9).

P6 Managing acute pulmonary embolism in the outpatient setting: initial experiences and outcomes in a UK district general hospital

Introduction and ObjectivesOutpatient (OP) management of low risk cases of pulmonary embolism (PE) can be as effective as inpatient (IP) management and reduce length of stay (LOS) (1). Concerns exist...

The EINSTEIN DVT Study: Does Localization of the Initial DVT Affect the Occurrence of Recurrent VTE While Patients Are on Anticoagulation?

Abstract 207 Background:The extent of deep vein thrombosis (DVT) is, for many physicians, an important variable that is considered in decisions on the type and duration of anticoagulant treatment. Although it has been consistently demonstrated that localization of the initial DVT is a powerful and independent predictor of recurrent venous thromboembolism (VTE) after discontinuation of anticoagulation (Baglin T et al. J Thromb Haemost 2010;8:2436–2442), it remains unknown to what extent localization of the initial DVT affects the occurrence of recurrent VTE while patients are on anticoagulation. Data from the EINSTEIN DVT study, which randomized 3,449 patients with proximal DVT, offers an opportunity to investigate this question. Aim:To investigate whether localization of the initial DVT was predictive of the rate of recurrent venous thromboembolic events in the whole cohort of patients in the EINSTEIN DVT study, in those who received rivaroxaban, or in those who received conventional anticoagulation with enoxaparin plus vitamin K antagonists (VKA) followed by VKA alone. Methods:Patients were randomized to rivaroxaban or enoxaparin plus VKA followed by VKA only for intended treatment durations of 3, 6, or 12 months. Patients were grouped into four categories according to the extent of the proximal vein thrombosis that was recorded at baseline: 1) popliteal vein alone; 2) popliteal and superficial femoral vein; 3) popliteal, superficial femoral, and common femoral vein; and 4) all combinations of DVT without popliteal vein involvement. Patients were followed for recurrent events. All baseline and recurrent events were assessed by a central independent adjudication committee that was unaware of treatment allocation. The effect of thrombus location on the incidence of recurrent VTE was assessed using a Cox proportional hazard model. Results:Recurrent VTE occurred in 21/1,040 (2.0%) patients with popliteal vein thrombosis only; in 28/1,002 (2.8%) patients with thrombosis located in the popliteal and superficial femoral vein; in 26/935 (2.8%) patients with thrombosis in the popliteal, superficial femoral, and common femoral vein (± iliac vein); and in 11/370 (3.0%) patients without popliteal vein involvement. None of these differences was statistically significant (p=0.87). The relative effect of rivaroxaban versus enoxaparin/VKA was similar in these subgroups (Table). Conclusions:At baseline, most patients in the EINSTEIN DVT study had thrombosis that involved more than one proximal vein. While patients were on treatment, the extent of the DVT at baseline was not predictive for recurrent VTE irrespective of type of treatment. Patients with extensive thrombosis (i.e. popliteal, superficial femoral, and common femoral vein involvement) had a recurrence rate below 3%, which was similar to the rate of recurrence in patients with thrombosis in only one vein at baseline. In summary, this analysis suggests that the localization and extent of the initial DVT was not predictive of the rate of recurrent venous thromboembolic events in the EINSTEIN DVT patient population while patients were on anticoagulation.Location of thrombus (vein)Incidence of recurrent eventsHazard ratio (95% confidence interval)Rivaroxaban n/n (%)Enoxaparin/VKA n/n (%)Popliteal only6/509 (1.2)15/531 (2.8)0.40 (0.15–1.02)Popliteal and superficial femoral12/525 (2.3)16/477 (3.4)0.67 (0.32–1.42)Popliteal, superficial femoral, and common femoral12/462 (2.6)14/473 (3.0)0.84 (0.39–1.81)Character count: 2670/3800 (spaces excluded) (2983 including table) Disclosures:Prins:Bayer HealthCare: Consultancy, Honoraria. Prandoni:GSK: Membership on an entity’s Board of Directors or advisory committees. Lensing:Bayer HealthCare AG: Employment. van Bellen:Bayer: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Pap:Bayer HealthCare AG: Employment. Raskob:Bayer: Consultancy, Honoraria; Johnson & Johnson: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Boehringer-Ingelhiem: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Sanofi-Aventis: Consultancy, Honoraria. Büller:Sanofi-aventis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Bayer HealthCare: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Bristol-Meyers Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Influence of Preceding Length of Anticoagulant Treatment and Initial Presentation of Venous Thromboembolism on Risk of Recurrence After Stopping Treatment: Analysis of Individual Participants' Data From Seven Trials

Conclusion: Risk of recurrent venous thromboembolism (VTE) after 3 months of anticoagulation therapy is similar to longer courses of anticoagulation. A higher risk of recurrence is present when the initial VTE event is a proximal deep venous thrombosis (DVT) or pulmonary embolism (PE). Summary: Randomized data indicate that at least 3 months of anticoagulation is preferable to shorter periods to reduce recurrent VTE after an initial VTE episode. Studies evaluating the optimal length of vitamin K antagonist treatment after VTE have compared two lengths of treatment. When only two lengths of treatment are compared, it is not possible to tell if the superior length of treatment from one individual study is the overall optimal length of treatment. The authors pooled data from seven individual comparative trials using a spectrum of lengths of treatment for VTE. The primary goal was to identify the shortest treatment length that most reduces the risk of recurrent VTE after stopping treatment with vitamin a K antagonist. They also sought to determine the optimal length of anticoagulant treatment with respect to specific subgroups at time of presentation VTE (proximal or distal DVT or PE) and whether thrombus recurrence was influenced by a temporary risk factor or whether the VTE was unprovoked. The seven studies comprised 2925 men and women with a first-time VTE event who did not have cancer. The primary end point was the first recurrent venous VTE event after stopping anticoagulation during up to 24 months of follow-up. The pooled data indicated recurrence was lower after isolated distal DVT then after proximal DVT (HR, 0.49; 95% CI, 0.34-0.71). Recurrence was similar after PE and proximal DVT (HR, 1.19; 95% CI, 0.87-1.63). Recurrence was lower after a VTE event associated with a temporary risk factor than after an unprovoked VTE (HR, 0.55; 95% CI, 0.41-0.74). Recurrence was similar if treatment was stopped at 3 months compared with 6 months or later (HR 1.19; 95% CI, 0.86-1.65). Recurrence was higher if anticoagulation was stopped at 1 or 1.5 months compared with 3 months or later (HR, 1.52; 95% CI, 1.14-2.02). Overall, higher rates of recurrence were associated with shorter durations of anticoagulation and were confined to the first 6 months after stopping vitamin K antagonist therapy. Comment: The analysis indicates patients with a VTE event who do not have an obvious indication for indefinite anticoagulation can stop vitamin K antagonist treatment after 3 months. Among the limitations of this study were that D-dimer levels and vascular laboratory assessment of the status of the venous thrombus at the end of anticoagulation were not included as potential variables influencing duration of anticoagulation. Perhaps patients with unprovoked VTE will, in the future, be better stratified by additional variables to determine which patients will have a low risk of recurrence with only 3 months of treatment.

Individualised strategy of warfarin treatment for deep vein thromboembolism – case reports

Individualised strategy of warfarin treatment for deep vein thromboembolism – case reports