546 publications from this institution
Patients with cancer commonly have a venous thromboembolism during the course of their disease.1 Venous thromboembolism in these patients leads to a high risk of recurrence and bleeding related to anticoagulant therapy.2 Furthermore, venous thromboembolism exposes patients with cancer to the risk of interruption of cancer treatment and may lead to otherwise unnecessary hospitalization. For these reasons, prevention of venous thromboembolism in ambulatory patients with cancer who are receiving chemotherapy is of potential clinical value. In two large, randomized, placebo-controlled trials3,4 and a comprehensive meta-analysis,5 all involving ambulatory patients with different types of metastatic or locally advanced solid cancer who . . .
Deep vein thrombosis (DVT) is a major health-care burden in Europe, but exact estimates are lacking. This study reports results from the PREFER venous thromboembolism (VTE) study concerning health-related quality of life (HrQoL) and mortality of patients with DVT.PREFER VTE was a prospective, observational study, conducted in 7 European countries, designed to provide data concerning treatment patterns, resource utilization, mortality, and QoL. First-time or recurrent patients with DVT were followed at 1, 3, 6, and 12 months. Health-related QoL-as measured by the EuroQoL 5-Dimension 5-Level instrument ( EQ-5D-5L)-was analyzed using Tobit regression with repeated measures, assessing the impact of baseline characteristics stratified by cancer activity. Mortality was analyzed using logistic regression.At baseline, patients with DVT had a 0.14 lower EQ-5D-5L index score (0.72 for total sample) compared to the reference UK population (0.85). The EQ-5D-5L index score improved from baseline to 12 months in patients with active cancer (from 0.70 to 0.79) and those without (0.72-0.87); 7.3% died within a year, a 5.2% excess mortality compared to the age- and gender-adfjusted general population. The 12-month mortality rate of DVT varied between 2.9% in the pooled data from Germany, Switzerland, or Austria and 15.4% in Italy. Furthermore, the mortality rate differed between patients with active cancer and those without (42.9% vs 4.7%).Deep vein thrombosis is associated with a substantial burden of illness in terms of HrQoL at baseline, which following treatment normalizes after 12 months and has a significant mortality rate. In addition, active cancer has a significant impact on mortality and the HrQoL of patients with DVT.
Abstract International and national guidelines recommend low-molecular-weight heparin for the treatment of venous thromboembolism (VTE) in patients with cancer. The aim of the Caravaggio study is to assess whether oral apixaban is non-inferior to subcutaneous dalteparin for the treatment of acute proximal deep vein thrombosis and/or pulmonary embolism in patients with cancer. The study is an investigator-initiated, multi-national, prospective, randomized, open-label with blind end-point evaluation (PROBE), non-inferiority clinical trial (NCT03045406). Consecutive patients are randomized to receive oral apixaban or subcutaneous dalteparin for 6 months. Apixaban is given at a dose of 10 mg twice daily for the first 7 days and then 5 mg twice daily; dalteparin is given at a dose of 200 IU/kg for the first month and then 150 IU/kg once daily. The primary outcome of the study is objectively confirmed recurrent VTE as assessed by a central independent adjudication committee unaware of study treatment allocation. The primary safety outcome is major bleeding defined according to the guidelines of the International Society of Thrombosis and Haemostasis. Assuming a 6-month incidence of the primary outcome of 7% with dalteparin and an upper limit of the two-sided 95% confidence interval of the hazard ratio below the pre-specified margin of 2.00, 1,168 patients will be randomized considering an up to 20% loss in total patient-years (β = 80%; α one-sided = 0.025). The Caravaggio study has the potential, along with other recently performed or on-going studies, to make less cumbersome the management of VTE in patients with cancer by replacing parenteral with oral anticoagulation.
The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE.In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications.Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 patients in each treatment group. A DVT was observed in 22 patients (14.1%) treated with enoxaparin and in 28 patients (18.0%) treated with placebo, corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31). No major bleeding occurred. Five patients (2.6%) in the enoxaparin group and two patients (1.0%) in the placebo group died during the treatment period.In this study, no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo. The dose of enoxaparin used in this study proved to be safe. Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication.
The role of anticoagulants for the prevention of venous thromboembolism in acute hemorrhagic stroke is uncertain. We performed an updated meta-analysis of studies to obtain the best estimates of the efficacy and safety of anticoagulants for the prevention of venous thromboembolism in patients with acute hemorrhagic stroke.Using electronic and manual searches of the literature, we identified randomized and non-randomized studies comparing anticoagulants (unfractionated heparin or low-molecular-weight heparin or heparinoids) with treatments other than anticoagulants (elastic stockings, intermittent pneumatic compression or placebo) in patients with acute hemorrhagic stroke. Study outcomes included symptomatic and asymptomatic deep venous thrombosis (DVT), symptomatic and asymptomatic pulmonary embolism (PE), any hematoma enlargement or death. Risk ratios (RRs) for individual outcomes were calculated for each study and data from all studies were pooled using the Mantel-Haenszel method.Four studies (two randomized) involving 1000 patients with acute hemorrhagic stroke met the criteria for inclusion in this meta-analysis. Compared with other treatments, anticoagulants were associated with a significant reduction in PE (1.7% vs. 2.9%; RR, 0.37; 95% CI, 0.17-0.80; P = 0.01), a DVT rate of 4.2% compared with 3.3% (RR, 0.77; 95% CI, 0.44-1.34; P = 0.36), an increase in any hematoma enlargement (8.0% vs. 4.0%; RR, 1.42; 95% CI, 0.57-3.53; P = 0.45), and a non-significant reduction in mortality (16.1% vs. 20.9%; RR, 0.76; 95% CI, 0.57-1.03; P = 0.07).Our findings indicate that in patients with hemorrhagic stroke, early anticoagulation is associated with a significant reduction in PE and a non-significant reduction in mortality, with the trade-off of a non-significant increase in hematoma enlargement. These results must be taken with caution and should encourage the assessment of the clinical benefit of antithrombotic prophylaxis in patients with cerebral bleeding by properly designed clinical trials.
Patients with unprovoked venous thromboembolism are at long-term risk for recurrence after discontination of oral anticoagulant treatment. Two years after treatment is withdrawn, the risk of recurrrence is about 20%. Although extending anticoagulant therapy reduces the recurrence risk, it is associated with increased bleeding. Aspirin therapy is effective in the primary prevention of venous thromboembolism, with risk reduction ranging from 20% to 50%. The possible benefit of aspirin for the prevention of recurrent venous thromboembolism is unknown. The aim of this multicenter, investigator-initiated, double-blind trial was to determine the clinical benefit of aspirin therapy for preventing recurrence in patients with unprovoked venous thromboembolism following a course of treatment with vitamin K antagonists. Subjects were patients older than 18 years who had completed 6 to 18 months of anticoagulant treatment for first-ever unprovoked venous thromboembolism . A total of 403 of these patients were randomized to receive once-daily treatment with aspirin 100 mg (n = 205) or placebo (n = 197) for 2 years, with the option of extending the study treatment. The primary efficacy outcome was recurrence of venous thromboembolism during a median study period of 24.6 months; the primary safety outcome was major bleeding. A secondary outcome was "on treatment" recurrence risk, which was examined during anticoagulant treatment and within 2 days after its withdrawal. Venous thromboembolism recurred significantly less frequently in 28 of the 205 patients who received aspirin compared with 43 of 197 of those who took placebo (6.6% vs 11.2% per year); the hazard ratio was 0.58, with a 95% confidence interval (CI) of 0.36 to 0.93 (P = 0.02). The on-treatment risk analysis showed that 23 patients in the aspirin group and 39 in the placebo group had a recurrence (5.9% vs 11.0% per year; hazard ratio, 0.55; 95% CI, 0.33–0.92; P = 0.02). There were 2 episodes of nonfatal major bleeding, one in each group. Adverse events were similar in the 2 groups. These findings show that aspirin therapy given after discontinuation of anticoagulant therapy in patients with unprovoked venous thromboembolism is effective in preventing recurrence, with no apparent increase in the risk of major bleeding.
<i>Background:</i> Hyperglycemia has been claimed to be associated with hemorrhagic transformation (HT) in patients with acute ischemic stroke treated with thrombolysis. The aim of this study was to assess whether the admission blood glucose level is related to HT in a prospective study in consecutive patients with acute ischemic stroke. <i>Methods:</i> Consecutive patients admitted for ischemic stroke to 4 Italian hospitals were included in this prospective cohort study. <i>Results:</i> Among 1,125 consecutive patients included in the analysis, 98 (8.7%) had HT: 62 (5.5%) had hemorrhagic infarction (HI) and 36 (3.2%) parenchymal hematoma (PH). A blood glucose level >110 mg/dl was found in 42.4% of the patients, a level between 110 and 149 mg/dl in 25.2%, and a level >150 mg/dl in 17.2%. At 3 months, 7 patients were lost at follow-up, 326 patients (29.2%) were disabled (modified Rankin score ≥3) and 129 died (11.5%). PH was associated with an increased risk of death or disability (OR 15.29, 95% CI 2.35–99.35). However, this was not the case for HT overall and HI. At logistic regression analysis, PH was predicted by high levels of admission blood glucose (OR 1.01, 95% CI 1.00–1.01 for 1 added mg/dl). The rate of PH was 2.1% in patients with <110 mg/dl, 3.6% in patients with a level between 110 and 149 mg/dl and 6.4% in patients with a level >150 mg/dl. The curve estimation regression model showed a significant linear increase in the risk of PH related to an increase in blood glucose levels (R<sup>2</sup> = 0.007, p = 0.007). <i>Conclusions:</i> Hyperglycemia during acute ischemic stroke predisposes to PH, which in turn determines a nonfavorable outcome at 3 months. This relationship seems to be linear.
Catheter angiography has been considered the standard of reference for the diagnosis of spontaneous cervical artery dissection (CAD), but carries a risk of complications and does not demonstrate the arterial wall. The most common angiographic finding is a relatively smooth or slightly irregular tapered arterial narrowing. Conversely, angiographic appearance of cervical artery occlusion due to CAD is nonspecific, because other causes such as thromboembolism or atherosclerotic disease may present very similar angiographic characteristics. Magnetic resonance imaging (MRI) is an alternative noninvasive approach and the only reliable possibility to diagnose occlusive dissection. MRI demonstrates the hyperintense, crescent- shaped wall hematoma and an eccentric flow void of the patent lumen. Intramural hematoma shows a typical evolution of signal intensity over time with intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images in the first 3 days. In the following days, most intramural hematoma show slightly or definitively increased signal intensity on T1- and T2-weighted images. After this, signal intensity of the hematoma increases and remains high for approximately 2 months. Magnetic resonance angiography shows the same findings as catheter angiography, and allows in combination with MRI to determine the extent of CAD.
