Tumor Site and Metastases as Predictors of Venous Thromboembolism Recurrence among Active Cancer Patients with Incident Deep Vein Thrombosis or Pulmonary Embolism: A Population-Based Cohort Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4096-4096
Author(s):  
Cheng E. Chee ◽  
John A. Heit ◽  
Aneel A. Ashrani ◽  
Tanya M. Petterson ◽  
Sara A. Farmer ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Independent Predictor ◽  
Tumor Site ◽  
Age And Gender ◽  
Vein Thrombosis ◽  
Recurrent Vte ◽  
And Gender ◽  
Deep Vein ◽  
Recurrence Group ◽  
Active Cancer

Abstract Background: Active cancer is an independent predictor of recurrent venous thromboembolism (VTE; hazard ratio=2.2–4.2). However, whether the risk of VTE recurrence among active cancer patients can be further stratified by tumor site or presence of metastases is uncertain. Objectives: To estimate and compare the cumulative incidence of VTE recurrence by tumor site and presence of metastases among active cancer patients with incident VTE. Study Design and Population: Retrospective cohort study of Olmsted County, MN residents with active cancer who lived >1 day after a first-lifetime deep vein thrombosis or pulmonary embolism over the 35-year period, 1966–2000 (n=418). 25 patients with oral (6), bone (1), skin (4), soft tissue (3), eye (1) and other/unknown (10) were excluded, leaving 393 remaining patients. Measurements: Baseline demographic and clinical characteristics, tumor site, presence and location of tumor metastases, and date of first recurrent VTE. Tumor site and metastases were tested as potential predictors of time-to-recurrent VTE using the Cox proportional hazards model. Results: 114 of 393 patients with active cancer developed recurrent VTE over 764 person-years of follow-up. The cumulative incidence of recurrent VTE at seven, 30, 90, and 180 days, 1, 5, and 10 years was 1.9%, 10.3%, 18.3%, 22.3%, 28.7%, 44.5%, and 53.5%, respectively. After adjusting for age and gender, tumor site was an independent predictor of first VTE recurrence (p<0.01). The hazard of VTE recurrence was over 2-fold higher for lung cancer patients compared to the lowest recurrence group (kidney, bladder and other genitourinary cancer; HR=2.04, 95% CI: 0.88, 4.70, p=0.096), and the hazard for brain and pancreatic cancer was nearly 2-fold higher (HR=1.9 for each, p=0.22, 0.24, respectively). The hazard of recurrence among hematological; breast and ovarian; gastric, colon, and liver; and prostate cancer patients did not differ significantly from the lowest recurrence group. Univariately, the presence of metastases at cancer diagnosis was not associated with recurrent VTE (HR=1.16; 95% CI: 0.79, 1.69, p=0.45). Conclusions: Tumor site is an independent predictor of VTE recurrence after adjusting for age and gender. In particular, lung, brain and pancreatic cancer patients have the highest risk for recurrence and these patients should be considered for secondary prophylaxis. Disease severity, as reflected by metastatic disease at cancer diagnosis, is not a predictor of recurrence.

Trends in the Incidence of Deep Vein Thrombosis and Pulmonary Embolism: A 35-Year Population-Based Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1488-1488 ◽  
Author(s):  
John A. Heit ◽  
Tanya M. Petterson ◽  
Sara A. Farmer ◽  
Kent R. Bailey ◽  
L. Joseph Melton
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Incidence Rates ◽  
Age And Gender ◽  
Vte Prophylaxis ◽  
Vein Thrombosis ◽  
And Gender ◽  
Age Adjusted Rates ◽  
Deep Vein ◽  
Age And Sex

Abstract Background: Recent trends in the incidence of venous thromboembolism (VTE), including idiopathic vs. non-idiopathic VTE, have not been well described. Objective: To estimate the incidence of deep vein thrombosis (DVT) and pulmonary embolism with or without DVT (PE), and describe trends in incidence. Methods: Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN residents with an incident DVT and PE over the 35-year period, 1966–2000 (n=3342). For all cases, the complete medical records in the community were reviewed for demographic and baseline characteristics previously identified as risk factors for VTE. Generalized linear models assuming a Poisson error structure, and using a log link function, and a log (population) offset will be used to assess the relationship of crude incidence rates to gender, year of diagnosis and age at diagnosis. Results: The overall average age- and sex-adjusted annual VTE incidence was 122 per 100,000 person-years (DVT, 56 per 100,000; PE, 66 per 100,000), with higher age-adjusted rates among men than women (134 versus 115 per 100,000, respectively). VTE incidence rates increased exponentially with age for both genders, ranging from 4 to 1110 per 100,000 for age groups 0–19 to 90–110 years. Compared to the 5-year period, 1981–85 (when non-invasive diagnostic testing became routinely available), the overall VTE incidence through 2000 remains unchanged. However, the DVT incidence and the PE incidence significantly increased and decreased, respectively, adjusting for age and gender (p<0.001 for both). The overall age- and sex-adjusted annual incidence of idiopathic VTE was 11.7 per 100,000 person-years (DVT, 6.6 per 100,000; PE, 5.1 per 100,000), with age-adjusted rates also higher among men than women (15.1 vs. 9.1 per 100,000). Interestingly, again compared to 1981–85, idiopathic VTE incidence decreased for 1991–95 (p=0.001) and 1996–2000 (p=0.32), adjusting for age and gender. Idiopathic DVT incidence decreased for 1991–95 (p=0.09), and idiopathic PE incidence decreased for both 1991–95 (p=0.004) and 1996–2000 (p=0.03). The overall age- and sex-adjusted annual incidence of non-idiopathic VTE was 109.4 per 100,000 (DVT, 48.4 per 100,000; PE, 60.7 per 100,000), again, with age-adjusted rates higher in men than women (115.1 vs. 106.8 per 100,000). Non-idiopathic DVT incidence increased steadily since 1981–85 (p=0.006, p<0.001, and p<0.001 for increasing DVT incidence for 1986–1990–1991–1995–1996–2000, respectively, adjusting for age and gender). Non-idiopathic PE incidence, however, remained unchanged for 1986–2000. Conclusions: VTE remains a major national health problem, especially among the elderly. Despite improved VTE prophylaxis efficacy and utilization, the overall incidence of VTE remains unchanged. However, the decreasing incidence of idiopathic DVT, and particularly idiopathic PE (with its associated poor survival) raises the possibility that the total number of VTE(PE)-related deaths may also be decreasing, albeit slightly. This hypothesis requires formal testing. The increasing or steady incidence of non-idiopathic DVT and PE, respectively, suggests the need for more widespread, effective VTE prophylaxis.

Subgroup Analysis of Patients with Cancer in Xalia - a Non-Interventional Study of Rivaroxaban in Routine Treatment of Deep Vein Thrombosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1438-1438 ◽  
Author(s):  
Alexander G G Turpie ◽  
Lorenzo G Mantovani ◽  
Sylvia Haas ◽  
Reinhold Kreutz ◽  
Danja Monje ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Research Funding ◽  
Incidence Rates ◽  
Vein Thrombosis ◽  
All Cause Mortality ◽  
Recurrent Vte ◽  
Deep Vein ◽  
Active Cancer

Abstract Background: XALIA is a prospective, non-interventional study of rivaroxaban in the treatment of acute deep vein thrombosis. The overall XALIA results showed that rivaroxaban was associated with similarly low rates of major bleeding and symptomatic recurrent venous thromboembolism (VTE) as standard anticoagulation. A subset of patients in XALIA had active cancer at the time of enrolment into the study. Purpose: To describe the demographics, clinical characteristics, treatment strategies and outcomes of patients in XALIA with cancer and VTE. The primary outcomes were major bleeding, recurrent VTE and all-cause mortality. Methods: Patients with deep vein thrombosis with or without concomitant pulmonary embolism aged ≥18 years who had active cancer and were scheduled to receive ≥3 months of anticoagulation with rivaroxaban or standard therapy were eligible. Therapy type, dose and duration were at the physician's discretion. For the purpose of this substudy, we defined the following treatment cohorts: rivaroxaban cohort (patients treated with rivaroxaban alone or who received heparin/fondaparinux for ≤48 hours before switching to rivaroxaban); early switchers cohort (patients treated with rivaroxaban who received heparin/fondaparinux for >48 hours-14 days and/or a vitamin K antagonist [VKA] for 1-14 days before changing to rivaroxaban); standard anticoagulation cohort (patients treated with heparin/fondaparinux and a VKA or a VKA only); and heparin/fondaparinux cohort (patients treated with heparin/fondaparinux alone). Results: Of 5136 patients in XALIA who received study medication, 587 (11.4%) had active cancer at baseline. Of these, 146 (24.9%) received rivaroxaban, 30 (5.1%) were early switchers, 167 (28.4%) received standard anticoagulation (of which 26 [4.4%] received a VKA only) and 244 (41.6%) received heparin/fondaparinux only, of whom 223 (38.0%) received low molecular weight heparin and the remainder other heparins or fondaparinux. Demographics are shown in Table 1. The most common type of active cancer at baseline in all cohorts was genitourinary, with the exception of the heparin/fondaparinux cohort where gastrointestinal cancer was the most common type (Table 2). The incidence rates for the primary outcomes for each cohort are shown in Figure 1. The rates of major bleeding were highest in the standard anticoagulation cohort (n=8 [4.8%]) and lowest in the early switchers (no major bleeding events occurred). The rates of recurrent VTE were similar in the in the rivaroxaban, early switcher and standard anticoagulation cohorts (n=5 [3.4%], n=1 [3.3%] and n=6 [3.6%], respectively) and were highest in the heparin/fondaparinux cohort (n=12 [4.9%]). All-cause mortality was highest in the heparin/fondaparinux cohort (n=61 [25.0%]) and lowest in the early switchers (no deaths occurred). Conclusions: In the real-world XALIA study, 38.0% of patients with cancer received treatment with low molecular weight heparin, which was in line with guidelines. The remaining patients received rivaroxaban, standard anticoagulation or were early switchers. For the three primary outcomes, the lowest incidence rates were observed in the early switcher cohort. The highest rates were in the standard anticoagulation cohort for major bleeding and the heparin/fondaparinux cohort for recurrent VTE and all-cause mortality; rates for all three primary outcomes were low in the rivaroxaban cohort, suggesting that rivaroxaban may be a safe and effective treatment option for patients with VTE and active cancer. Figure 1 Primary outcomes in patients with active cancer at baseline by treatment group. VTE, venous thromboembolism. Figure 1. Primary outcomes in patients with active cancer at baseline by treatment group. / VTE, venous thromboembolism. Disclosures Turpie: Janssen Research & Development, LLC: Consultancy, Honoraria; Bayer Pharma AG: Consultancy, Honoraria. Mantovani:Janssen-Cilag Ltd: Research Funding; Boehringer Ingelheim: Research Funding; Daiichi Sankyo: Consultancy; Bayer Pharma AG: Consultancy; Pfizer Inc: Research Funding. Haas:Sanofi SA: Consultancy; Pfizer Inc: Consultancy; Daiichi Sankyo: Consultancy; Bristol-Myers Squibb: Consultancy; Bayer Pharma AG: Consultancy; Aspen Pharmacare: Consultancy. Kreutz:Bayer Pharma AG: Honoraria; Servier Laboratories Ltd: Consultancy; Lundbeck Ltd: Consultancy; Daiichi Sankyo: Consultancy; Berlin-Chemie Menarini: Consultancy; Bayer Pharma AG: Consultancy; Bristol-Myers Squibb: Honoraria; Daiichi Sankyo: Honoraria. Monje:Bayer Pharma AG: Employment. Schneider:Bayer Pharma AG: Employment. van Eickels:Bayer Pharma AG: Employment. Gebel:Bayer Pharma AG: Employment. Ageno:Boehringer Ingelheim: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Bayer Pharmaceuticals: Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Bayer Pharma AG: Consultancy, Honoraria.

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

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19645-e19645
Author(s):  
Suebpong Tanasanvimon ◽  
Naveen Garg ◽  
Chitra Viswanathan ◽  
Milind M. Javle ◽  
Mylene Truong ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Metastatic Disease ◽  
Vena Cava ◽  
Cancer Center ◽  
Vein Thrombosis ◽  
Gonadal Vein ◽  
Radiology Reports ◽  
Recurrent Vte ◽  
Active Cancer

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.

Intensity of Heparin Anticoagulation as an Independent Predictor of 14-Day Recurrence after Deep Vein Thrombosis or Pulmonary Embolism: A Population-Based Cohort Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 873-873
Author(s):  
John A. Heit ◽  
Brian K. Lahr ◽  
Tanya M. Petterson ◽  
Kent R. Bailey ◽  
L. Joseph Melton
Keyword(s):  
Warfarin Therapy ◽  
Independent Predictor ◽  
Female Gender ◽  
Heparin Therapy ◽  
Neurologic Disease ◽  
Vein Thrombosis ◽  
Heparin Anticoagulation ◽  
Deep Vein ◽  
Anticoagulation Intensity ◽  
Active Cancer

Abstract Background: Most trials of standard heparin and warfarin therapy used the 3- to 6-month cumulative incidence of venous thromboembolism (VTE) recurrence as the primary efficacy outcome. Consequently, the effect of heparin anticoagulation intensity on short-term VTE recurrence after controlling for other predictors of recurrence (e.g., active cancer, neurological disease with extremity paresis) is uncertain. Objectives: To test standard heparin anticoagulation intensity, using activated partial prothrombin time (APTT) data, as an independent predictor of 14-day VTE recurrence. Measurements: Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN residents with an incident deep vein thrombosis or pulmonary embolism over the 14-year period, 1984–1997 (n=1165). We followed each case (conditional on surviving one day) forward in time through their complete medical records in the community for first VTE recurrence. We collected date of incident VTE onset, start and stop dates of heparin and warfarin, and date, time and result of all APTT and platelet count values. Using these and other measures of standard heparin therapy as time-dependent variables, we tested the intensity of heparin anticoagulation as an independent predictor of 14-day VTE recurrence while controlling for other baseline characteristics using Cox proportional hazards modeling. Results: Of the 1165 patients, 1026 (88%) and 989 (85%) received heparin and warfarin, respectively, and 254 (22%) developed recurrent VTE over 5461 person-years of follow-up; 23 recurred within 14 days. In the multivariate analysis, the independent predictors of 14-day recurrence included female gender (HR=3.06, 95%CI: 1.05, 8.91; p=0.04) and neurologic disease with extremity paresis (HR=6.01, 95%CI: 1.93, 18.66; p&lt;0.01); the hazard of recurrence was marginally increased for active cancer (HR=2.21, p=0.13). Warfarin therapy (HR=0.44, p=0.11) and a therapeutic APTT within the first 24 hours of therapy (HR=0.41, p=0.08) were marginally protective, but age, body mass index, time interval between VTE onset and start of heparin, and other measures of heparin anticoagulation intensity (e.g., proportion of time in therapeutic APTT range, etc) were not predictors of recurrence. Three patients developed new and persistent thrombocytopenia beginning 2, 4 and 5 days after starting heparin, respectively and prior to VTE recurrence. Conclusions: VTE recurrence is uncommon within 14 days after starting heparin therapy. Female gender and neurologic disease with extremity paresis are independent predictors of 14-day recurrence, and active cancer may be an additional predictor. Warfarin therapy and a therapeutic APTT within the first 24 hours may predict a reduced recurrence risk. However, other measures of heparin anticoagulation intensity were non-predictive. Heparin-induced thrombocytopenia may partially account for early VTE recurrence.

The Optimal Duration of Anticoagulant Therapy In Patients with Cancer-Related Deep Vein Thrombosis: The Advantage of Using Residual Vein Thrombosis (the Cancer-DACUS Study)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 190-190 ◽  
Author(s):  
Sergio Siragusa ◽  
Alessandra Malato ◽  
Doris Mascheroni ◽  
Walter Ageno ◽  
Eugenio Bucherini ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Recurrent Events ◽  
Lower Limbs ◽  
Vein Thrombosis ◽  
Optimal Duration ◽  
Group B ◽  
Deep Vein ◽  
Active Cancer

Abstract Abstract 190 Type and duration of anticoagulation is still matter of debate in cancer patients with acute Deep Vein Thrombosis (DVT) of the lower limbs. Residual Vein Thrombosis (RVT) has been proven to be effective for assessing the optimal duration of oral anticoagulants in non cancer patients (Siragusa S et al Blood 2008:112:511-5). In the present study we evaluate the role of a RVT-based management of anticoagulation with Low-Molecular Weight Heparin in cancer patients with acute DVT. Materials and Methods. Patients with active cancer and a first episode of DVT were treated with LMWH for 6 months (the first month at full dosage followed by dose reduction of 25% in the next 5 months). At the end of treatment, they were managed according to RVT findings: those with RVT were randomized to continue anticoagulants for 6 additional months (Group A1) or to stop it (Group A2), while patients without RVT stopped LMWH (Group B). Outcomes were recurrent venous thromboembolism and/or major bleeding; patients were followed up for one year after LMWH discontinuation. Results. Over a period of 36 months, 409 patients were evaluated; 62 were excluded (refusal, need for continuing anticoagulation, etc). In total, 347 were included in the study (Table 1). RVT was detected in 242 (69.7%) patients; recurrent events occurred in 21.9% of those randomized to discontinue and 14.2% of those who continued LMWH. In patients without RVT (105, 30.3%), recurrent events occurred in 3 cases (2.8%) (Table 2 and Figure 1). The adjusted Hazard Ratio (HR) for age and sex between RVT groups (Group A2 vs A1) was 1.58 (95% confidence interval [CI], 0.85–2.93; P=.145). The adjusted HR between group A1 versus RVT-negative group (B) was 4.54 (CI 2.3–6.66; P =.028). Five major bleeding events occurred in Group A1 and two events both in Group A2 and B (Table 2). Overall, 89 (25.6%) patients died due to cancer progression after a median follow-up of 10.2 months after heparin withdrawn. Conclusions. The Cancer DACUS is the first ever study evaluating an individual marker for assessing duration of anticoagulation in active cancer population. Final results of the study show that absence of RVT identifies a group of patients at low risk for recurrent thrombosis who can safely stop LMWH after 6 months. Disclosures: No relevant conflicts of interest to declare.

Venous thromboembolism in patients with active cancer

2007 ◽  
Vol 98 (09) ◽  
pp. 656-661 ◽  
Author(s):  
Ali Seddighzadeh ◽  
Ranjith Shetty ◽  
Samuel Goldhaber
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Inferior Vena ◽  
The United States ◽  
Inferior Vena Caval ◽  
Vte Prophylaxis ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Deep Vein ◽  
Active Cancer

SummaryPatients with cancer have an increased risk of venous thromboembolism (VTE).To further define the demographics, comorbidities, and risk factors of VTE in these patients, we analyzed a prospective registry of 5,451 patients with ultrasound confirmed deep vein thrombosis (DVT) from 183 hospitals in the United States. Cancer was reported in 1,768 (39%), of whom 1,096 (62.0%) had active cancer. Of these, 599 (54.7%) were receiving chemotherapy, and 226 (20.6%) had metastases. Lung (18.5%), colorectal (11.8%), and breast cancer (9.0%) were among the most common cancer types. Cancer patients were younger (median age 66 years vs. 70 years; p<0.0001), were more likely to be male (50.4% vs. 44.5%; p=0.0005), and had a lower average body mass index (26.6 kg/m2 vs. 28.9 kg/m2; p<0.0001). Cancer patients less often received VTE prophylaxis prior to development of DVT compared to those with no cancer (308 of 1,096, 28.2% vs. 1,196 of 3,444, 34.6%; p<0.0001). For DVT therapy, low-molecular-weight heparin (LMWH) as monotherapy without warfarin (142 of 1,086, 13.1% vs. 300 of 3,429, 8.7%; p<0.0001) and inferior vena caval filters (234 of 1,086, 21.5% vs. 473 of 3,429, 13.8%; p<0.0001) were utilized more often in cancer patients than in DVT patients without cancer. Cancer patients with DVT and neurological disease were twice as likely to receive inferior vena caval filters than those with no cancer (odds ratio 2.17, p=0.005). In conclusion, cancer patients who develop DVT receive prophylaxis less often and more often receive filters than patients with no cancer who develop DVT. Future studies should focus on ways to improve implementation of prophylaxis in cancer patients and to further define the indications, efficacy, and safety of inferior vena caval filters in this population.

Intensity of Warfarin Anticoagulation as an Independent Predictor of 6-Month Recurrence after Deep Vein Thrombosis or Pulmonary Embolism: A Population-Based Cohort Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 718-718
Author(s):  
John A. Heit ◽  
Brian K. Lahr ◽  
Tanya M. Petterson ◽  
Kent R. Bailey ◽  
L. Joseph Melton
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Warfarin Therapy ◽  
Independent Predictor ◽  
Heparin Therapy ◽  
Independent Effect ◽  
Vein Thrombosis ◽  
Deep Vein ◽  
Anticoagulation Intensity ◽  
Active Cancer

Abstract Background: Most trials of standard heparin and warfarin therapy used the 3- to 6-month cumulative incidence of venous thromboembolism (VTE) recurrence as the primary efficacy outcome. However, the independent effect of warfarin anticoagulation intensity on VTE recurrence after controlling for other predictors of recurrence (e.g., active cancer, neurological disease with extremity paresis) is uncertain. Objectives: To test warfarin anticoagulation intensity, using international normalized ratio (INR) data, as an independent predictor of 6-month VTE recurrence. Measurements: Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN residents with an incident deep vein thrombosis or pulmonary embolism over the 14-year period, 1984–1997 (n=1165). We followed each case (conditional on surviving 14 days without VTE recurrence) forward in time through their complete medical records in the community for first VTE recurrence. We collected date of incident VTE onset, start and stop dates of heparin and warfarin, and date, time and result of all INR values. Using these and other measures of standard warfarin therapy as time-dependent variables, we tested the intensity of warfarin anticoagulation (expressed as the cumulative percent of time with an INR at or above 2.0 [or at or above 1.5] while on warfarin) as an independent predictor of 6-month VTE recurrence while controlling for other baseline characteristics using Cox proportional hazards modeling. Results: Of the 1165 patients, 1026 (88%) and 989 (85%) received heparin and warfarin, respectively, and 254 (22%) developed recurrent VTE over 5461 person-years of follow-up; 52 recurred within 15–180 days. In the multivariate analysis, the independent predictor of 6-month recurrence was active cancer (HR=3.98, 95% CI: 2.12, 7.45; p&lt;0.01); age, gender, body mass index and neurologic disease with extremity paresis were not predictors of VTE recurrence. In models that included presence or absence of warfarin therapy along with proportion of time with an INR ≥2, this latter intensity variable was protective (HR=0.16 for 100% versus 0% of time, p=0.02) against recurrence, while mere presence of warfarin therapy (HR =0.72, p= 0.56) was not. Similar results were obtained when intensity was represented as proportion of time with an INR ≥1.5 (HR=0.17, p=0.02). Interestingly, a therapeutic APTT within the first 24 hours of heparin therapy also was protective against 6-month recurrence (HR=0.45, p=0.02). Conclusions: Active cancer is an independent predictor of 6-month VTE recurrence. Warfarin therapy with a higher proportion of time with an INR ≥1.5 or ≥2 offers similar protection against recurrence. A rapid heparin-response (as reflected by a therapeutic APTT within 24 hours of heparin therapy) also is a predictor of reduced 6-month recurrence, possibly reflecting lower factor VIII activity at the acute incident VTE event. Gender is not a predictor of long-term recurrence.

Residual Vein Obstruction (RVO) Predicts Recurrence for Cancer Patients with Secondary VTE: A Meta-Analysis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2259-2259
Author(s):  
Murali Janakiram ◽  
Matt R Sullivan ◽  
Marina Shcherba ◽  
Shuang Guo ◽  
Henny Heisler Billett
Keyword(s):  
Clinical Trials ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Vein Thrombosis ◽  
Patients With Cancer ◽  
Recurrent Vte ◽  
Deep Vein ◽  
Residual Vein Obstruction

Abstract Abstract 2259 Background: Venous thrombosis is a common disease and long term anticoagulation is effective in the prevention of venous thromboembolism (VTE). Studies to detect residual vein obstruction (RVO) performed at the end of the anticoagulation period has been investigated as a predictive marker for recurrent thrombotic risk. The value of this test has been questioned, and different methodologies, different patient populations, and varying lengths of prior anticoagulation may be responsible for the disparate results published. In order to assess the true predictive worth of RVO we performed a meta-analysis of published studies to determine whether RVO can predict the risk of recurrent VTE. Methods: A comprehensive literature search with the terms “deep vein thrombosis”, “residual vein thrombosis“, and “recurrent venous thromboembolism” was performed on PubMed, MEDLINE, EMBASE, Web of Science, the Cochrane dataset, Science Direct and CINAHL. Clinical trials published in English between January 1990 and December 2011 were eligible for this analysis. The selection of abstracts was based on the following criteria: studies had to be prospective, VTE patients had to have been anticoagulated with unfractionated heparin, low molecular weight heparin or warfarin for at least 6 weeks, and the presence of RVO and recurrent thromboembolic events had to have been recorded. The diagnosis of RVO was allowed if 1) a venous thrombosis of >2mm was present 2) the thrombus occupied >40% of vein diameter or 3) the presence of positive thrombosis on duplex was noted. Recurrent events were defined if a new contralateral deep vein thrombosis (DVT), a new ipsilateral DVT (if the prior DVT was documented to be recanalised) or a new PE (documented by perfusion scan, Computed Tomographic Angiography or pulmonary angiography) was noted. Data were analyzed with STATS Direct meta-analysis software. Analyses were performed for the whole VTE population as well as for unprovoked and provoked VTE cohorts. A sub-analysis of patients with cancer within the provoked cohort was performed. Odds Ratios (OR) with 95% confidence intervals were calculated for individual studies and Forrest plots were generated. Results: We identified 1955 potential publications, of which 28 were relevant. Thirteen studies met inclusion criteria and were included in the final analysis. 4546 patients, mean age 61years, with 3476 events were included. Five studies were prospective studies which recruited patients with only primary VTE, four studies examined secondary VTE only and four studies investigated both primary and secondary VTE. For all patients with VTE, primary and secondary, the presence of RVO was associated with a significantly higher recurrent VTE risk (OR 1.93. 95%CI: 1.29 –2.89, p = 0.001). When analyzed separately for primary VTE, RVO did not demonstrate a statistically significant increased recurrent VTE risk (OR 1.38, 95%CI: 0.87 – 2.08), results consistent with prior observations. When results were analyzed for patients with secondary VTE, the OR was 2.78 (95% CI: 1.4 – 5.5, p= 0.003). However, when patients with cancer were eliminated from the secondary VTE cohort, the OR decreased to 1.73 and was no longer significant (95% CI: 0.82 – 3.66). In contrast, for the two studies with cancer patients, the odds ratio for recurrent VTE given a positive RVO study was 5.14 (95% CI: 1.59 – 16.65 p = 0.006). While RVO studies showed recanalization and/or normalization after 6 months in 93% of post-operative patients, recanalization occurred in only 53% of patients who were treated for cancer, only 20% of patients with active cancer had negative RVO studies. Conclusions: A meta-analysis of 13 studies examining the predictive value of RVO studies did not detect significant utility for patients with primary VTE. RVO predicted recurrence in secondary VTE but subset analysis demonstrated that RVO seems to have predictive value primarily in the subgroup of patients with cancer. Current ACCP and NCCN guidelines for thrombosis in cancer differ in their recommemdation for duration of anticoagulation but both recommend extended anticoagulant therapy. A negative RVO study might reliably predict a group which might not need extended anticoagulation. Further prospective clinical trials are needed determining the utility of RVO in cancer patients with VTE. Disclosures: No relevant conflicts of interest to declare.

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

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS9149-TPS9149 ◽  
Author(s):  
Agnes Y. Lee ◽  
Rupert Bauersachs ◽  
Mette S. Janas ◽  
Mikala F. Jarner ◽  
Pieter W Kamphuisen ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Cancer Patients ◽  
Randomized Study ◽  
Predictive Biomarkers ◽  
Healthcare Resource Utilization ◽  
Open Label ◽  
Vein Thrombosis ◽  
Recurrent Vte ◽  
Wells Rule ◽  
Active Cancer

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 > 160 sites in >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).

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