Incidental Pulmonary Embolism. Analysis of Mayo Clinic Venous Thromboembolism Database

Background: Incidental pulmonary embolism (PE) is not infrequently found on CT scans with highest incidence reported in patients with cancer. It is unclear whether patients with symptomatic pulmonary embolism (iPE) have different clinical profile or outcomes compared to patients with symptomatic PE (sPE) and whether this is affected by the presence or type of malignancy. Objective: Compare baseline characteristics of patients diagnosed with iPE to patients with sPE with attention to cancer-specific risk factors as well as evaluate clinical outcomes. Methods: Consecutive patients enrolled in the Mayo Thrombophilia Clinic VTE Registry between March 1, 2013 and December 31st, 2018 with PE were followed prospectively. Outcomes of recurrent venous thromboembolism (VTE), major bleeding, clinically relevant non-major bleeding (CRNMB) and mortality data were collected every 3 months. Clinical outcomes were analyzed with specific focus on patients with cancer. Information was collected and managed using REDCap (Research Electronic Data Capture) and data analysis was performed using SAS software (SAS Institute Inc., Cary, North Carolina). Results: Out of a total of 1033 patients with PE in VTE registry, there were 655 patients with PE (284 with incidental and 363 symptomatic) who completed at least 3 months of anticoagulation and were started on treatment within 14 days of diagnosis. Apixaban was used in 220 (34 %), Rivaroxaban 175 (27 %), Enoxaparin 179 (27%), and Warfarin in 81 (12 %) patients. Overall cancer was present in 61% of patients and was more common in patients with iPE compared to sPE (80.2% vs 45.2%, p<0.001). Patients with iPE were less likely to have previous VTE (8.2% vs 25.5%, p< 0.0001) and tended to have lower BMI (mean 28.8 vs 31.4, p<0.0001) Characteristics of the subgroup of only cancer patients with PE are summarized in the Table. Of note, pancreatic and GI cancers were more common in patients with iPE. There were no differences in recurrent VTE, major bleeding and CRNMB in patients with iPE compared to sPE. This also held true for patients with underlying malignancies. Mortality rates were significantly higher in all patients with iPE even when adjusting for presence of malignancy (p=0.03). When adjusting for presence of metastatic malignancy though the difference was no longer present (p=0.33). Conclusion: Patients with iPE were more likely to have an underlying malignancy, potentially due to higher likelihood of undergoing staging imaging studies. Additionally, patients with iPE more often had metastatic disease which was associated with higher mortality. Recurrent VTE and bleeding outcomes were similar in patients with iPE and sPE, this was independent of the presence of underlying malignancy. Disclosures McBane: BMS: Research Funding.

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Treatment and Long-Term Clinical Outcomes of Incidental Pulmonary Embolism in Patients With Cancer: An International Prospective Cohort Study

Journal of Clinical Oncology ◽

10.1200/jco.18.01977 ◽

2019 ◽

Vol 37 (20) ◽

pp. 1713-1720 ◽

Cited By ~ 29

Author(s):

Noémie Kraaijpoel ◽

Suzanne M. Bleker ◽

Guy Meyer ◽

Isabelle Mahé ◽

Andrés Muñoz ◽

...

Keyword(s):

Pulmonary Embolism ◽

Cohort Study ◽

Venous Thromboembolism ◽

Clinical Outcomes ◽

Major Bleeding ◽

Cumulative Incidence ◽

Patients With Cancer ◽

Incidental Pulmonary Embolism ◽

Recurrent Venous Thromboembolism

PURPOSE Pulmonary embolism is incidentally diagnosed in up to 5% of patients with cancer on routine imaging scans. The clinical relevance and optimal therapy for incidental pulmonary embolism, particularly distal clots, is unclear. The aim of the current study was to assess current treatment strategies and the long-term clinical outcomes of incidentally detected pulmonary embolism in patients with cancer. PATIENTS AND METHODS We conducted an international, prospective, observational cohort study between October 22, 2012, and December 31, 2017. Unselected adults with active cancer and a recent diagnosis of incidental pulmonary embolism were eligible. Outcomes were recurrent venous thromboembolism, major bleeding, and all-cause mortality during 12 months of follow-up. Outcome events were centrally adjudicated. RESULTS A total of 695 patients were included. Mean age was 66 years and 58% of patients were male. Most frequent cancer types were colorectal (21%) and lung cancer (15%). Anticoagulant therapy was initiated in 675 patients (97%), of whom 600 (89%) were treated with low-molecular-weight heparin. Recurrent venous thromboembolism occurred in 41 patients (12-month cumulative incidence, 6.0%; 95% CI, 4.4% to 8.1%), major bleeding in 39 patients (12-month cumulative incidence, 5.7%; 95% CI, 4.1% to 7.7%), and 283 patients died (12-month cumulative incidence, 43%; 95% CI, 39% to 46%). The 12-month incidence of recurrent venous thromboembolism was 6.4% in those with subsegmental pulmonary embolism compared with 6.0% in those with more proximal pulmonary embolism (subdistribution hazard ratio, 1.1; 95% CI, 0.37 to 2.9; P = .93). CONCLUSION In patients with cancer with incidental pulmonary embolism, risk of recurrent venous thromboembolism is significant despite anticoagulant treatment. Patients with subsegmental pulmonary embolism seemed to have a risk of recurrent venous thromboembolism comparable to that of patients with more proximal clots.

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Risk of Recurrent Venous Thromboembolism and Major Bleeding in Cancer-Associated Incidental Pulmonary Embolism Amongst Treated and Untreated Patients: A Pooled Analysis of 926 Patients

Blood ◽

10.1182/blood.v124.21.590.590 ◽

2014 ◽

Vol 124 (21) ◽

pp. 590-590 ◽

Cited By ~ 2

Author(s):

T van der Hulle ◽

P L den Exter ◽

G Meyer ◽

B Planquette ◽

S Soler ◽

...

Keyword(s):

Pulmonary Embolism ◽

Venous Thromboembolism ◽

Major Bleeding ◽

Individual Patient Data ◽

Incidence Rates ◽

Patient Data ◽

Anticoagulant Treatment ◽

Incidental Pulmonary Embolism ◽

Recurrent Venous Thromboembolism ◽

Recurrent Vte

Abstract Introduction Incidental pulmonary embolism (IPE) is defined as a pulmonary embolism diagnosed on a CT-scan performed for reasons other than a clinical suspicion of PE. Generally identified on staging scans, IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. In order to determine the outcome more accurately, and to identify clinical characteristics related to the prognosis, we pooled individual patient data from eleven observational studies and ongoing registries. Methods A systematic literature search aiming to identify studies reporting on patients diagnosed with cancer-associated IPE was performed. Authors of selected studies were invited to participate. Incidence rates of objectively diagnosed symptomatic recurrent venous thromboembolism (VTE), major bleeding and mortality during 6-month follow-up were pooled. Individual patient data was collected to perform subgroup analyses, for which all patients were considered as one cohort. Hazard ratios (HR) were adjusted for age, sex and cancer stage. Results Individual patient data of 926 cancer patients with IPE from 11 observational studies and ongoing registries were included (Table 1). The overall pooled 6-month risk of symptomatic recurrent VTE was 5.8% (95%CI 3.7-8.3), of major bleeding 4.7% (95%CI 3.0-6.8) and of mortality 37% (95%CI 28-47). The VTE recurrence risk was comparable in patients treated with VKA and LMWH with incidence rates of 6.4% (95%CI 2.2-12) and 6.2% (95%CI 3.5-9.6), HR 0.89 (95%CI 0.27-2.9). In contrast, this incidence rate was 12% (95%CI 4.7-23) in patients who were left untreated, HR 2.9 (95%CI 0.65-13; Figure 1). The risk of major bleeding was significantly higher in patients treated with VKA compared to those treated with LMWH, 13% (95%CI 6.4-20) versus 3.9% (95%CI 2.3-5.9), HR of 3.2 (95%CI 1.4-7.4) (Figure 2). The 6-month mortality was 37% (95%CI 29-44) in patients treated with LMWH, 28% (95%CI 18-40) in those treated with VKA and 47% (95%CI 28-66) amongst untreated patients. The all-cause mortality at 6 months was significantly higher for patients with a central thrombus (either central or lobar) compared to those with a more peripheral IPE (either segmental or subsegmental); 42% (95%CI 33-52) versus 30% (95%CI 25-36, HR 1.8 (95%CI 1.4-2.3). Conclusions The most important finding of this study is the 12% 6-month risk of symptomatic recurrent VTE in patients with cancer-associated IPE who did not receive anticoagulant treatment, which is more than double the risk of patients who were anticoagulated. These numbers recall the effect size of anticoagulants used in symptomatic PE and support the judicious initiation of anticoagulant treatment in cancer-associated IPE. The association between more centrally-located thrombi and mortality following IPE is a new finding that parallels outcomes for symptomatic PE, and one which may further support similar management. Regarding the choice of anticoagulant, VKA were associated with a significantly higher risk of major bleeding than LMWH, with a comparable risk of recurrent VTE. The findings of this observational study should be preferably confirmed in a randomized trial. Figure 1: Figure 1:. The 6-month risk of recurrent venous thromboembolism related to anticoagulant treatment. Figure 2: The 6-month risk of major bleeding related to anticoagulant treatment. Figure 2:. The 6-month risk of major bleeding related to anticoagulant treatment. Abstract 590. Table 1: Baseline characteristics Treatment All patients n=926 (100%) LMWH n=732 (79%) VKA n=100 (11%) No treatment n=53 (6%) Other treatment n=41 (4%) Mean age (SD) 65 (12) 64 (12) 68 (12) 65 (14) 68 (13) Male sex, n (%) 491 (53) 378 (52) 60 (60) 31 (58) 22 (54) Cancer stage, n (%) Metastatic 501 (54) 400 (55) 56 (56) 33 (62) 12 (29) Non-metastatic 192 (21) 143 (20) 34 (34) 12 (23) 3 (7.3) Unspecified 233 (25) 189 (26) 10 (10) 8 (15) 26 (63) Cancer type, n (%) Lung 176 (19) 135 (18) 16 (16) 18 (34) 7 (17) Colorectal 185 (20) 150 (20) 20 (20) 9 (17) 6 (15) Other gastrointestinal 187 (20) 147 (20) 15 (15) 13 (25) 12 (29) Breast 65 (7.0) 52 (7.1) 10 (10) 1 (1.9) 2 (4.9) Gynaecological 64 (6.9) 56 (7.7) 5 (5.0) 0 (0) 3 (7.3) Other 206 (22) 155 (21) 31 (31) 10 (19) 10 (24) Haematological 43 (4.6) 37 (5.1) 3 (3.0) 2 (3.8) 1 (2.4) Largest artery involved, n (%) Central 292 (32) 230 (31) 30 (30) 11 (21) 21 (51) Peripheral 495 (53) 395 (54) 62 (62) 29 (55) 9 (22) Unspecified 139 (15) 107 (15) 8 (8.0) 13 (25) 11 (27) Disclosures No relevant conflicts of interest to declare.

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Abstract 12901: Novel Oral Anticoagulants Are Associated With Decreased Recurrence of Venous Thromboembolism in Patients With Cancer: An Updated Meta-Analysis

Circulation ◽

10.1161/circ.142.suppl_3.12901 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Sunil Upadhaya ◽

Seetharamprasad Madala ◽

Sunil Badami

Keyword(s):

Venous Thromboembolism ◽

Major Bleeding ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Novel Oral Anticoagulants ◽

P Value ◽

Patients With Cancer ◽

Randomized Controlled ◽

All Cause Mortality ◽

Recurrent Vte

Introduction: Patients with cancer are at high risk for recurrent thromboembolic phenomenon. Use of novel oral anticoagulants (NOAC) for treatment of venous thromboembolism (VTE) in such patients is controversial. We conducted this updated meta-analysis to evaluate the pooled efficacy and safety of NOAC in patients with cancer. Methods: We did systematic search of PubMed and Cochrane library databases for randomized controlled trials comparing NOAC with low molecular weight heparin (LMWH) for VTE treatment in cancer patients till April 2020. The efficacy outcomes were recurrent VTE and all-cause mortality rates, and the primary safety outcome was incidence of major bleeding rate. Results: Four randomized controlled studies comparing NOAC with LMWH (1446 patients in NOAC group and 1448 patients in LMWH group) were included in our study. Use of NOAC lead to significant reduction in recurrent VTE rate (odds ratio (OR): 0.55 [0.36-0.84], I 2 = 45 %, p value = 0.006) (Figure 1). However, we did not find any significant difference in rate of major bleeding (OR: 1.30 [0.76-2.23], I 2 = 35%, p value = 0.34) (Figure 2) and all-cause mortality (OR: 1 [0.80 - 1.26], I 2 = 33%, p value = 0.98). Conclusions: This updated meta-analysis showed comparatively lower pooled recurrent VTE rate in patient being treated with NOAC, whereas similar rates of major bleeding and all-cause death. NOAC are more efficacious and has similar safety profile compared with LMWH.

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Vitamin K Antagonists Compared to Low-Molecular-Weight Heparins for Treatment of Cancer-Associated Venous Thromboembolism: An Observational Study in Routine Clinical Practice

Thrombosis and Haemostasis ◽

10.1160/th-17-06-0382 ◽

2017 ◽

Vol 117 (11) ◽

pp. 2163-2167 ◽

Cited By ~ 1

Author(s):

Paul den Exter ◽

José Hooijer ◽

Tom van der Hulle ◽

Julien van Oosten ◽

Olaf Dekkers ◽

...

Keyword(s):

Molecular Weight ◽

Clinical Practice ◽

Venous Thromboembolism ◽

Vitamin K ◽

Major Bleeding ◽

Routine Clinical Practice ◽

Bleeding Complications ◽

Low Molecular Weight ◽

Patients With Cancer ◽

Recurrent Vte

AbstractSince several trials have demonstrated that low-molecular-weight-heparin (LMWH) is superior to vitamin K antagonist (VKA) in preventing recurrent venous thromboembolism (VTE) in patients with cancer-associated VTE, guidelines now recommend LMWH monotherapy in this setting. We evaluated whether this shift resulted in improved outcomes in routine clinical practice. We performed a cohort study of consecutive patients with cancer-associated VTE during 2001 and 2010. We compared the risks for recurrent VTE, major bleeding and mortality between patients diagnosed before and after 2008 during a 6-month routine follow-up. A total of 381 patients were included, of which 234 (61.4%) were diagnosed before 2008. Before 2008, 23% of the patients were treated with LMWH; thereafter, this percentage was higher: 67%. The 6-month incidence for recurrent VTE was 8.6% in patients diagnosed before 2008 versus 7.5% for patients diagnosed after 2008 (risk difference [RD]: −1.1%; 95% confidence interval [CI]: −6.3, 5.3). The respective risks for major bleeding were 6.4 versus 4.8% (RD: −1.6%; 95% CI: −3.8 to 5.8), and 39.7 versus 41.5% (RD: 1.8%; 95% CI: −8.8, 12) for overall mortality. The mean time in therapeutic range (TTR) of patients treated with VKA was 61%. Despite a clear shift toward LMWH as agent of choice for cancer-associated VTE, we did not observe a clear improvement in terms of recurrent VTE and bleeding complications.

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Clinical course of pulmonary embolism patients treated with DOACs: comparing prognosis, recurrent thromboembolism, and major bleeding between patients with and without cancer

European Heart Journal ◽

10.1093/ehjci/ehaa946.2279 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

Y Nakano ◽

R Imai ◽

M Yoshida ◽

S Shimokata ◽

S Adachi ◽

...

Keyword(s):

Pulmonary Embolism ◽

Major Bleeding ◽

Cumulative Incidence ◽

Clinical Course ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Patients With Cancer ◽

Kaplan Meier ◽

Significant Difference ◽

Recurrent Vte

Abstract Background Venous thromboembolism (VTE) is the third frequent acute cardiovascular syndrome in the Europe and Japan. Since direct oral anticoagulants (DOACs) are widely used now, the morbidity and mortality of pulmonary embolism (PE) patients especially associated with cancer needs to be re-evaluated. Purpose We evaluated the clinical course of patients with PE mainly treated with DOACs. Methods This retrospective observational study was conducted in a single center. The data were collected from the medical record of consecutive patients who received inpatient treatment of PE. In this study, we have compared PE patients with cancer (cancer PE) to those without cancer (non-cancer PE) and evaluated the mortality, recurrent of VTE and major bleedings. Results In total, 140 patients were enrolled: 94 patients were cancer-related, and 46 patients were without cancer (Table). The type of the tumor in cancer PE patients were as follows: gastric 8 (9%), esophageal 5 (5%), pancreatic 12 (13%), lung 14 (15%), lymphoma 2 (2%), gynecologic 17 (18%), renal 2 (2%), bile duct 8 (9%), colon 12 (13%), and others 17 (18%). Kaplan-Meier curve showed that the cumulative all-cause mortality was significantly higher in the cancer PE group (35/94 (37%) vs. 2/46 (4%), P<0.001 (log rank), HR 10.3 [95% CI:2.5–43.3]). The cumulative incidence of recurrent VTE was significantly higher in the cancer PE group (7/94 (7%) vs. 0/46, P=0.03 (log rank)). There was no significant difference in the cumulative incidence of major bleeding between the cancer PE group and the non-cancer PE group (8/94 (9%) vs. 5/46 (11%)). Conclusions The risk of recurrent VTE was still higher in cancer PE patients compared to non-cancer PE patients, although DOACs were used. Meanwhile the incidence of major bleeding was comparable in both groups, the risk of bleeding might be acceptable with using DOACs especially in cancer PE patients. Figure 1 Funding Acknowledgement Type of funding source: None

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Validation of the Ottawa Score in Cancer Patients with Venous Thromboembolism. the Predicare Cohort Study

Blood ◽

10.1182/blood-2019-129087 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 167-167 ◽

Cited By ~ 1

Author(s):

Guy Meyer ◽

Celine Chapelle ◽

Philippe Girard ◽

Florian Scotté ◽

Anne Lamblin ◽

...

Keyword(s):

Cohort Study ◽

Venous Thromboembolism ◽

Board Of Directors ◽

Cancer Patients ◽

Major Bleeding ◽

Research Funding ◽

Advisory Committees ◽

Patients With Cancer ◽

Recurrent Vte ◽

Support Research

Introduction Venous thromboembolism (VTE) is a difficult to treat condition in patients with cancer with a persisting risk of recurrent VTE during anticoagulant treatment with low-molecular weight heparin (LMWH). Recent data suggest that direct oral anticoagulants (DOACS) are associated with a lower risk of recurrence but a higher risk of bleeding in these patients. Predicting the risk of recurrent VTE with LMWH may help to select the best treatment option. We conducted a prospective multicenter observational cohort study in cancer patients with VTE treated with tinzaparin for 6 months in order to validate the Ottawa score (NCT03099031) and search for additional risk of recurrent VTE. The Ottawa score is composed of 5 variables, female sex (+1), lung cancer (+1), breast cancer (-1) cancer stage 1 (-2) and previous DVT (+1). A score ≤0 is associated with a low risk of recurrent VTE. Methods Adult cancer patients with recent diagnosis of documented symptomatic or incidental VTE (deep vein thrombosis (DVT) or pulmonary embolism (PE) treated with tinzaparin for 6 months were included in the study. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment with tinzaparin. Other endpoints were symptomatic recurrent VTE, major bleeding, heparin induced thrombocytopenia (HIT), all-cause mortality within 3 and 6 months. All events were adjudicated by a Central Adjudication Committee. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. Cumulative incidences were presented with corresponding 95% confidence interval (95% CI). To validate the Ottawa score, the area under the curve (AUC) and its 95% CI were calculated on receiver operating characteristic (ROC) curve analysis; the most discriminant cut-off was then determined by calculating the Youden index. Univariate and multivariate analyses were performed to identify additional predictive factors of recurrent VTE to those included in the Ottawa score using the Fine and Gray method and adjusted on factors included in the Ottawa score. Hazard ratio and their 95% CI were calculated. Results A total of 409 patients were included and analyzed on an intention-to-treat basis; the median age was 68 years and 51% of patients were males. 60.4% of patients had a PE (with or without DVT) .64% received chemotherapy at inclusion or in the month before inclusion. Lung (31.3%) and digestive track (18.3%) cancers were the most common cancer types and 67.0% had stage IV cancers. According to Ottawa score, 58% of patients were classified at high clinical probability of recurrence (score ≥ 1). During the 6 months treatment period, 23 patients had a recurrent VTE, yielding a cumulative incidence of 6.1% (95% CI 4.0-9.3) with a median time for recurrent VTE of 33 days. The recurrence rate of VTE was estimated to 7.8% (95% CI 4.9-12.5) for patients classified at high risk of recurrence according to the Ottawa score (score ≥ 1) compared to 3.8% (95%CI 1.6-8.9) for other patients (Ottawa score < 1). AUC of the Ottawa score was 0.60 (95% CI 0.55-0.65). In multivariable analysis, none of the potential risk factors for recurrent VTE was significantly associated with recurrent VTE at 6 months. During the 6 months treatment period, 15 patients had a major bleeding and 2 patients experienced a HIT. At 3 and 6 months, 104 and 144 patients had died yielding a cumulative incidence of 26.1%, (95% CI 21.8-30.4) and 37.8% (95% CI 32.8-42.9), respectively. The main cause of death was underlying cancer. Conclusion In this prospective cohort of patients with cancer receiving LMWH for VTE, the Ottawa score did not accurately predict recurrent VTE. No other clinical predictor of recurrent VTE was identified in this study. Disclosures Meyer: Bayer: Other: travel support; LEO pharma: Other: travel support, Research Funding; SANOFI: Other: travel support, Research Funding; BMS-Pfizer: Other: travel support, Research Funding; Boehringer Ingelheim: Research Funding. Girard:Leo Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Scotté:LEO Pharma A/S: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Tesaro: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Research Funding, Speakers Bureau; MSD: Honoraria, Research Funding, Speakers Bureau; Pierre Fabre Oncology: Honoraria, Research Funding, Speakers Bureau. Lamblin:Leo Pharma: Employment. Laporte:Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boston scientific: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Leo-Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer-Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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Renal Impairment, Recurrent Venous Thromboembolism and Bleeding in Cancer Patients with Acute Venous Thromboembolism—Analysis of the CATCH Study

Thrombosis and Haemostasis ◽

10.1055/s-0038-1641150 ◽

2018 ◽

Vol 118 (05) ◽

pp. 914-921 ◽

Cited By ~ 13

Author(s):

Agnes Lee ◽

Pieter Kamphuisen ◽

Guy Meyer ◽

Mette Janas ◽

Mikala Jarner ◽

...

Keyword(s):

Venous Thromboembolism ◽

Renal Impairment ◽

Major Bleeding ◽

Open Label ◽

Exact Test ◽

Patients With Cancer ◽

Recurrent Vte ◽

Cancer Associated Thrombosis ◽

Acute Venous Thromboembolism ◽

The Impact

Objective This article assesses the impact of renal impairment (RI) on the efficacy and safety of anticoagulation in patients with cancer-associated thrombosis from the Comparison of Acute Treatments in Cancer Hemostasis (CATCH) study (NCT01130025). Materials and Methods Renal function was assessed using the Modification of Diet in Renal Disease equation in patients with cancer-associated thrombosis who received either tinzaparin (175 IU/kg) once daily or warfarin for 6 months, in an open-label, randomized, multi-centre trial with blinded adjudication of outcomes. Associations between baseline RI (glomerular filtration rate [GFR] <60 mL/min/1.73m2) and recurrent symptomatic or incidental venous thromboembolism (VTE), clinically relevant bleeding (CRB), major bleeding and death were assessed using Fisher's exact test. Results Baseline-centralized GFR data were available for 864 patients (96% of study population). RI was found in 131 patients (15%; n = 69 tinzaparin). Recurrent VTE occurred in 14% of patients with and 8% of patients without RI (relative risk [RR] 1.74; 95% confidence interval [CI] 1.06, 2.85), CRB in 19% and 14%, respectively (RR 1.33; 95% CI 0.90, 1.98), major bleeding in 6.1% and 2.0%, respectively (RR 2.98; 95% CI 1.29, 6.90) and mortality rate was 40% and 34%, respectively (RR 1.20; 95% CI 0.94, 1.53). Patients with RI on tinzaparin showed no difference in recurrent VTE, CRB, major bleeding or mortality rates versus those on warfarin. Conclusion RI in patients with cancer-associated thrombosis on anticoagulation was associated with a statistically significant increase in recurrent VTE and major bleeding, but no significant increase in CRB or mortality. No differences were observed between long-term tinzaparin therapy and warfarin.

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Clinical outcome of patients with major bleeding after venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th08-06-0390 ◽

2008 ◽

Vol 100 (05) ◽

pp. 789-796 ◽

Cited By ~ 48

Author(s):

José Nieto ◽

Timoteo Camara ◽

Elena Gonzalez-Higueras ◽

Nuria Ruiz-Gimenez ◽

Ricardo Guijarro ◽

...

Keyword(s):

Pulmonary Embolism ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Vena Cava ◽

Vena Cava Filter ◽

Fatal Bleeding ◽

History Of ◽

Recurrent Vte ◽

Overall Mortality

SummaryThe natural history of patients with venous thromboembolism (VTE) who develop a major bleeding complication while on anticoagulant therapy is not well known. RIETE is a prospective registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. The clinical characteristics, treatment decisions and outcome of all VTE patients who had major bleeding during the first three months of anticoagulant therapy were retrospectively studied. As of January 2007, 17,368 patients were included in RIETE. Of these, 407 (2.3%) had major bleeding during the study period: 144 gastrointestinal, 119 haematoma, 51 intracranial, 43 genitourinary, 50 other. In 286 (69%) patients anticoagulant therapy was discontinued, in 74 (18%) not modified, in 38 (9.1%) a vena cava filter was inserted. During the first 30 days after bleeding, 24 (5.9%) patients re-bled, 20 (4.9%) had recurrent VTE, 133 (33%) died. Of these, 75 died of bleeding, 12 of recurrent pulmonary embolism. Most deaths occurred shortly after the bleeding episode (median:1 day).On multivariate analysis, insertion of a vena cava filter was the only variable independently associated with a lower incidence of fatal bleeding (odds ratio [OR]: 0.10; 95% confidence interval [CI]: 0.01–0.79) and all-cause mortality (OR: 0.21; 95%CI: 0.07–0.63). In conclusion, the occurrence of major bleeding in patients with VTE is outstanding in terms of overall mortality (33% within 30 days), fatal bleeding (18%) or re-bleeding (5.9%). However, these patients also have an increased incidence of recurrent VTE (4.9%) and fatal pulmonary embolism (1.2%).

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Outcomes of low-molecular-weight heparin treatment for venous thromboembolism in patients with primary and metastatic brain tumours

Thrombosis and Haemostasis ◽

10.1160/th16-09-0680 ◽

2017 ◽

Vol 117 (03) ◽

pp. 589-594 ◽

Cited By ~ 6

Author(s):

Chatree Chai-Adisaksopha ◽

Lori-Ann Linkins ◽

Said Y. ALKindi ◽

Matthew Cheah ◽

Mark A. Crowther ◽

...

Keyword(s):

Venous Thromboembolism ◽

Brain Tumour ◽

Major Bleeding ◽

Brain Tumours ◽

Retrospective Chart Review ◽

P Value ◽

Patients With Cancer ◽

Tumour Group ◽

Recurrent Vte ◽

And Gender

SummaryVenous thromboembolism (VTE) is one of the most common complications in patients with brain tumours. There is limited data available in the literature on VTE treatment in these patients. We conducted a matched retrospective cohort study of patients with primary or metastatic brain cancer who were diagnosed with cancer-associated VTE. Patients were selected after a retrospective chart review of consecutive patients who were diagnosed with cancer-associated VTE between January 2010 and January 2014 at the Juravinski Thrombosis Clinic, Hamilton, Canada. Controls were age- and gender-matched patients with cancer-associated VTE from the same cohort, but without known brain tumours. A total of 364 patients with cancer-associated VTE were included (182 with primary or metastatic brain tumours and 182 controls). The median follow-up duration was 6.7 (interquartile range 2.5–15.8) months. The incidence rate of recurrent VTE was 11.0 per 100 patient-years (95 % CI; 6.7–17.9) in patients with brain tumours and 13.5 per 100 patient-years (95 % CI; 9.3–19.7) in non-brain tumour group. The incidence of major bleeding was 8.6 per 100 (95 % CI; 4.8–14.7) patient-years in patients with brain tumours versus 5.0 per 100 patient-years (95 % CI; 2.8–9.2) in controls. Rate of intracranial bleeding was higher in brain tumour patients (4.4 % vs 0 %, p-value=0.004). In summary, rates of recurrent VTE and major bleeding were not significantly different in patients with cancer-associated VTE in the setting of primary or metastatic brain tumours compared those without known brain tumours. However, greater numbers of intracranial bleeds were observed in patients with brain tumours.

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Direct oral anticoagulants for cancer-associated venous thromboembolism: a systematic review and meta-analysis

Blood ◽

10.1182/blood.2020005819 ◽

2020 ◽

Vol 136 (12) ◽

pp. 1433-1441 ◽

Cited By ~ 5

Author(s):

Frits I. Mulder ◽

Floris T. M. Bosch ◽

Annie M. Young ◽

Andrea Marshall ◽

Robert D. McBane ◽

...

Keyword(s):

Systematic Review ◽

Venous Thromboembolism ◽

Major Bleeding ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Controlled Trials ◽

Efficacy And Safety ◽

Patients With Cancer ◽

Recurrent Vte

Abstract Direct oral anticoagulants (DOACs) are an emerging treatment option for patients with cancer and acute venous thromboembolism (VTE), but studies have reported inconsistent results. This systematic review and meta-analysis compared the efficacy and safety of DOACs and low-molecular-weight heparins (LMWHs) in these patients. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and conference proceedings were searched to identify relevant randomized controlled trials. Additional data were obtained from the original authors to homogenize definitions for all study outcomes. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Other outcomes included the composite of recurrent VTE and major bleeding, clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. Summary relative risks (RRs) were calculated in a random effects meta-analysis. In the primary analysis comprising 2607 patients, the risk of recurrent VTE was nonsignificantly lower with DOACs than with LMWHs (RR, 0.68; 95% CI, 0.39-1.17). Conversely, the risks of major bleeding (RR, 1.36; 95% CI, 0.55-3.35) and CRNMB (RR, 1.63; 95% CI, 0.73-3.64) were nonsignificantly higher. The risk of the composite of recurrent VTE or major bleeding was nonsignificantly lower with DOACs than with LMWHs (RR, 0.86; 95% CI, 0.60-1.23). Mortality was comparable in both groups (RR, 0.96; 95% CI, 0.68-1.36). Findings were consistent during the on-treatment period and in those with incidental VTE. In conclusion, DOACs are an effective treatment option for patients with cancer and acute VTE, although caution is needed in patients at high risk of bleeding.

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