ALBERT

Description: Abstract LBA-1 Background: Following acute deep vein thrombosis (DVT) of the lower limb, approximately 1 in 4 patients treated with anticoagulation (AC) and elastic compression stockings (ECS) in accordance with current guidelines, are still at risk for developing a chronically reduced functional outcome, i.e., the post-thrombotic syndrome (PTS). Additional treatment with catheter-directed thrombolysis (CDT) enhances clot removal and is suggested to favor venous competence and patency, thereby reducing the risk for PTS. This interventional therapy is expensive, associated with life-threatening bleeding, and converts an outpatient disease to an inpatient disease. However, it has become standard care in some centers despite a complete lack of evidence from randomized, controlled trials (RCT). The CaVenT study, representing the first RCT in this area, aimed to evaluate whether additional CDT with alteplase improved the functional outcome by reducing PTS development following acute iliofemoral DVT. Methods: The CaVenT study was an open, multicenter RCT that recruited patients from 20 hospitals in the Norwegian south-eastern health region. Patients of age 18–75 years with a first-time objectively verified acute iliofemoral DVT above mid-thigh level and symptoms for up to 21 days were eligible for recruitment. Study patients were randomly assigned with a 1:1 ratio to standard (control) treatment with AC and ECS grade II (30 mmHg) or to CDT with alteplase in addition to standard treatment. The present report concerns the primary clinical end-point; the frequency of PTS after 24 months follow-up. The study was designed to detect a reduction in PTS from 25% to 10% with a 5% significance level and with 80% power. Follow-up visits were conducted at 6 months ± 2 weeks and 24 months ± 4 weeks and included evaluation of PTS by the Villalta scale as recommended by the International Society on Thrombosis and Haemostasis. Iliofemoral patency was assessed with ultrasonography and air-plethysmography. A two-sided uncorrected Chi-square test was used for comparing dichotomous variables in the two treatment groups. Results: 209 patients with acute iliofemoral DVT were randomized during 2006–2009; 101 patients were allocated the CDT arm and 108 the control arm. At the completion of 24 months follow-up, data on clinical status were available and included in the intention to treat analyzes for 90 patients in the CDT arm and 99 control patients. Mean age was 51.5 years (SD 15.8), 36% were female, and mean duration of symptoms was 6.6 days (SD 4.6). 80/90 patients receiving CDT had successful lysis. At 24 months follow-up 37 (41.1%, 95% CI 31.5–51.4%) allocated additional CDT presented with PTS compared to 55 (55.6%, 95% CI 45.7–65.0%) in the control group (p=0.047), including one control with severe PTS. The difference in PTS corresponds to an absolute risk reduction of 14.4% (95% CI 0.2–27.9), and the number needed to treat was 7 (95% CI 4–502). No patients presented with venous ulcer. In total 20 bleeding complications were reported; 3 were classified as major and 5 as clinically relevant. The majority of bleedings were related to the puncture site. The major bleedings included 1 abdominal wall hematoma requiring blood transfusion, 1 compartment syndrome of the calf requiring surgery, and 1 inguinal puncture site hematoma. No bleeding led to a permanently reduced outcome, and there were no deaths, pulmonary embolism or cerebral hemorrhage related to CDT. Patients who had regained venous patency after 6 months, developed PTS in 38/103 (36.9%, 95% CI 28.2–46.5%) as compared to 49/80 (61.3%, 95% CI 50.3–71.2%) of patients with insufficient recanalization (p

Description: LBA-1 Background: Following acute deep vein thrombosis (DVT) of the lower limb, approximately 1 in 4 patients treated with anticoagulation (AC) and elastic compression stockings (ECS) in accordance with current guidelines, are still at risk for developing a chronically reduced functional outcome, i.e., the post-thrombotic syndrome (PTS). Additional treatment with catheter-directed thrombolysis (CDT) enhances clot removal and is suggested to favor venous competence and patency, thereby reducing the risk for PTS. This interventional therapy is expensive, associated with life-threatening bleeding, and converts an outpatient disease to an inpatient disease. However, it has become standard care in some centers despite a complete lack of evidence from randomized, controlled trials (RCT). The CaVenT study, representing the first RCT in this area, aimed to evaluate whether additional CDT with alteplase improved the functional outcome by reducing PTS development following acute iliofemoral DVT. Methods: The CaVenT study was an open, multicenter RCT that recruited patients from 20 hospitals in the Norwegian south-eastern health region. Patients of age 18–75 years with a first-time objectively verified acute iliofemoral DVT above mid-thigh level and symptoms for up to 21 days were eligible for recruitment. Study patients were randomly assigned with a 1:1 ratio to standard (control) treatment with AC and ECS grade II (30 mmHg) or to CDT with alteplase in addition to standard treatment. The present report concerns the primary clinical end-point; the frequency of PTS after 24 months follow-up. The study was designed to detect a reduction in PTS from 25% to 10% with a 5% significance level and with 80% power. Follow-up visits were conducted at 6 months ± 2 weeks and 24 months ± 4 weeks and included evaluation of PTS by the Villalta scale as recommended by the International Society on Thrombosis and Haemostasis. Iliofemoral patency was assessed with ultrasonography and air-plethysmography. A two-sided uncorrected Chi-square test was used for comparing dichotomous variables in the two treatment groups. Results: 209 patients with acute iliofemoral DVT were randomized during 2006–2009; 101 patients were allocated the CDT arm and 108 the control arm. At the completion of 24 months follow-up, data on clinical status were available and included in the intention to treat analyzes for 90 patients in the CDT arm and 99 control patients. Mean age was 51.5 years (SD 15.8), 36% were female, and mean duration of symptoms was 6.6 days (SD 4.6). 80/90 patients receiving CDT had successful lysis. At 24 months follow-up 37 (41.1%, 95% CI 31.5–51.4%) allocated additional CDT presented with PTS compared to 55 (55.6%, 95% CI 45.7–65.0%) in the control group (p=0.047), including one control with severe PTS. The difference in PTS corresponds to an absolute risk reduction of 14.4% (95% CI 0.2–27.9), and the number needed to treat was 7 (95% CI 4–502). No patients presented with venous ulcer. In total 20 bleeding complications were reported; 3 were classified as major and 5 as clinically relevant. The majority of bleedings were related to the puncture site. The major bleedings included 1 abdominal wall hematoma requiring blood transfusion, 1 compartment syndrome of the calf requiring surgery, and 1 inguinal puncture site hematoma. No bleeding led to a permanently reduced outcome, and there were no deaths, pulmonary embolism or cerebral hemorrhage related to CDT. Patients who had regained venous patency after 6 months, developed PTS in 38/103 (36.9%, 95% CI 28.2–46.5%) as compared to 49/80 (61.3%, 95% CI 50.3–71.2%) of patients with insufficient recanalization (p

Description: Conventional treatment of acute deep vein thrombosis (DVT) is anticoagulation and compression therapy (Grade 1A recommendations). Following adequate conventional treatment approximately every fourth patient with proximal DVT of the lower limb develop postthrombotic syndrome (PTS). PTS evolves from persistent venous obstruction and/or venous insufficiency caused by inflammatory destruction of the venous valves. Both obstruction and insufficiency of the veins may lead to venous hypertension. Accelerating the removal of venous thrombus by thrombolytic agents is suggested to prevent the development of PTS. Case-series have shown technical and thrombolytic success, however, the ongoing CaVenT Study is the first randomized, controlled trial to evaluate short- and long-term effects of venous catheter-directed thrombolysis (CDT). Our main hypothesis on short-term effects is that CDT in first-time acute DVT increases patency of the affected iliofemoral vein segments after 6 months from 80% after adjunctive CDT. From January 2006 to January 2008 103 patients (64 male, mean age 52.1 years) were randomized to receive either adjunctive CDT (n=50) or conventional treatment alone (n=53). After CDT 50–90% lysis (grade II lysis) was achieved in 20 patients, and complete lysis (grade III) in 24 patients. CDT failed in one patient with agenesis of inferior vena cava, and 1 patient was denied CDT because the thrombus did not reach the upper half of the thigh at initiation of the procedure. Non-invasive assessment of the veins performed at 6 months follow-up, included ultrasound with Doppler and air plethysmography. Patients with incompressibility of the femoral vein, no venous flow and/or functional venous obstruction were classified as not having regained iliofemoral venous patency. Patients with duplicate femoral veins with at least one branch with normal compressibility and flow were considered successfully recanalized. Venous insufficiency was defined as reflux lasting 〉0.5 sec. Patency of the iliofemoral vein segments was found in 32 (64.0%) patients in the CDT group and 19 (35.8%) in the control group, corresponding to a risk difference (RD) of 28.2% (95% CI, 9.7% to 46.7%, p=0.004). Functional venous obstruction was found in 10 (20.0%) patients in the CDT group and in 26 (49.1%) controls, corresponding to a RD of 29.1% (95% CI, 20.0% to 38.0%, p=0.004). There were no significant differences between the groups regarding the other subcategories of patency (absence of iliofemoral flow and incompressibility of femoral vein), other postthrombotic changes of the iliofemoral veins (wall thickening and echoic content of vein lumen), or femoral venous insufficiency. The results indicate that adjunctive CDT increases patency 6 months after iliofemoral DVT, from 36% to 64%. Venous obstruction, but not venous insufficiency was reduced in the CDT group. The clinical relevance of these findings will be assessed when future data from 2 years follow-up are available. Any future documentation of long-term improved functional outcome, i.e., a reduction in PTS, in this patient group will have a significant impact on clinical practice, and may lead to a modification of existing international guidelines.