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      Clinical implications of incidental venous thromboembolism in cancer patients

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          Abstract

          Introduction

          In cancer patients, current guidance suggests similar treatment for incidental and symptomatic venous thromboembolism (VTE), mainly based on retrospective data. We aimed to evaluate anticoagulant therapy in cancer patients with incidental and symptomatic VTE.

          Methods

          The Hokusai VTE Cancer Study was a randomised controlled trial comparing edoxaban with dalteparin for cancer-associated VTE. The primary outcome was the composite of first recurrent VTE or major bleeding. Secondary outcomes included major bleeding, recurrent VTE and mortality. Outcomes in patients with incidental and symptomatic VTE were evaluated during the 12-month study period.

          Results

          331 patients with incidental VTE and 679 patients with symptomatic VTE were enrolled, of whom the index event was confirmed by an independent radiologist. Median durations of anticoagulant treatment were 195 and 189 days, respectively. In patients with incidental VTE, the primary outcome occurred in 12.7% of patients, major bleeding in 6.6% of patients and recurrent VTE in 7.9% of patients. Out of the 26 VTE recurrences in patients with incidental VTE, five (31%) were incidental, seven (44%) were symptomatic and four (25%) were deaths for which pulmonary embolism could not be ruled out. In patients with symptomatic VTE, the primary outcome occurred in 13.8% of patients, major bleeding in 4.9% of patients and recurrent VTE in 10.9% of patients. All-cause mortality was similar in both groups.

          Conclusion

          Clinical adverse outcomes are substantial in both cancer patients with incidental and symptomatic VTE, supporting current guideline recommendations that suggest treating incidental VTE in the same manner as symptomatic VTE.

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          Most cited references15

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          Epidemiology of cancer-associated venous thrombosis.

          Cancer-associated venous thrombosis is a common condition, although the reported incidence varies widely between studies depending on patient population, start and duration of follow-up, and the method of detecting and reporting thrombotic events. Furthermore, as cancer is a heterogeneous disease, the risk of venous thrombosis depends on cancer types and stages, treatment measures, and patient-related factors. In general, cancer patients with venous thrombosis do not fare well and have an increased mortality compared with cancer patients without. This may be explained by the more aggressive type of malignancies associated with this condition. It is hypothesized that thromboprophylaxis in cancer patients might improve prognosis and quality of life by preventing thrombotic events. However, anticoagulant treatment leads to increased bleeding, particularly in this patient group, so in case of proven benefit of thromboprophylaxis, only patients with a high risk of venous thrombosis should be considered. This review describes the literature on incidence of and risk factors for cancer-associated venous thrombosis, with the aim to provide a basis for identification of high-risk patients and for further development and refinement of prediction models. Furthermore, knowledge on risk factors for cancer-related venous thrombosis may enhance the understanding of the pathophysiology of thrombosis in these patients.
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            A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose-Ranging Study.

            We performed a randomized dose-ranging study, double-blind for rivaroxaban doses and open-label for the comparator (low-molecular-weight heparin followed by vitamin K antagonists) to assess the optimal dose of rivaroxaban for the treatment of deep vein thrombosis. A total of 543 patients with acute deep-venous thrombosis received rivaroxaban 20, 30, or 40 mg once daily or comparator. Treatment lasted for 84 days. The primary efficacy outcome was the 3-month incidence of the composite of symptomatic venous thromboembolic complications and asymptomatic deterioration in thrombotic burden as assessed by comparison of ultrasound and perfusion lung scanning at day 84 with baseline. The main safety outcome was the composite of major bleeding and clinically relevant nonmajor bleeding. A total of 449 (83%) of the 543 patients could be included in the per-protocol population. The primary efficacy outcome occurred in 6.1%, 5.4%, and 6.6% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 9.9% of those receiving standard therapy. The main safety outcome occurred in 5.9%, 6.0%, and 2.2% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 8.8% of those receiving standard therapy. These results with simple fixed-dose oral regimens justify phase 3 evaluations (www.ClinicalTrials.gov no.NCT00395772).
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              Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies.

              Multiple-detectors computed tomographic pulmonary angiography (CTPA) has a higher sensitivity for pulmonary embolism (PE) within the subsegmental pulmonary arteries as compared with single-detector CTPA. Multiple-detectors CTPA might increase the rate of subsegmental PE diagnosis. The clinical significance of subsegmental PE is unknown. We sought to summarize the proportion of subsegmental PE diagnosed with single- and multiple-detectors CTPA and assess the safety of diagnostic strategies based on single- or multiple-detectors CTPA to exclude PE. A systematic literature search strategy was conducted using MEDLINE, EMBASE and the Cochrane Register of Controlled Trials. We selected 22 articles (20 prospective cohort studies and two randomized controlled trials) that included patients with suspected PE who underwent a CTPA and reported the rate of subsegmental PE. Two reviewers independently extracted data onto standardized forms. The rate of subsegmental PE diagnosis was 4.7% [95% confidence interval (CI): 2.5-7.6] and 9.4 (95% CI: 5.5-14.2) in patients that underwent a single- and multiple-detectors CTPA, respectively. The 3-month thromboembolic risks in patients with suspected PE and who were left untreated based on a diagnostic algorithm including a negative CTPA was 0.9% (95% CI: 0.4-1.4) and 1.1% (95% CI: 0.7-1.4) for single- and multiple-detectors CTPA, respectively. Multiple-detectors CTPA seems to increase the proportion of patients diagnosed with subsegmental PE without lowering the 3-month risk of thromboembolism suggesting that subsegmental PE may not be clinically relevant. © 2010 International Society on Thrombosis and Haemostasis.
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                Author and article information

                Journal
                European Respiratory Journal
                Eur Respir J
                European Respiratory Society (ERS)
                0903-1936
                1399-3003
                February 06 2020
                February 2020
                February 2020
                November 14 2019
                : 55
                : 2
                : 1901697
                Article
                10.1183/13993003.01697-2019
                31727694
                73378c7e-0349-49e3-a2e3-9a24b78b89fe
                © 2019

                https://www.ersjournals.com/user-licence

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