Extended-Duration Venous Thromboembolism Prophylaxis in Acutely Ill Medical Patients With Recently Reduced Mobility

BACKGROUND: Extended-duration low-molecular-weight heparin has been shown to prevent venous thromboembolism (VTE) in high-risk surgical patients. OBJECTIVE: To evaluate the efficacy and safety of extended-duration enoxaparin thromboprophylaxis in acutely ill medical patients. DESIGN: Randomized, parallel, placebo-controlled trial. Randomization was computer-generated. Allocation was centralized. Patients, caregivers, and outcome assessors were blinded to group assignment. (ClinicalTrials.gov registration number: NCT00077753) SETTING: 370 sites in 20 countries across North and South America, Europe, and Asia. PATIENTS: Acutely ill medical patients 40 years or older with recently reduced mobility (bed rest or sedentary without [level 1] or with [level 2] bathroom privileges). Eligibility criteria for patients with level 2 immobility were amended to include only those who had additional VTE risk factors (age >75 years, history of VTE, or active or previous cancer) after interim analyses suggested lower-than-expected VTE rates. INTERVENTION: Enoxaparin, 40 mg/d subcutaneously (2975 patients), or placebo (2988 patients), for 28 +/- 4 days after receiving open-label enoxaparin for an initial 10 +/- 4 days. MEASUREMENTS: Incidence of VTE up to day 28 and of major bleeding events up to 48 hours after the last study treatment dose. RESULTS: Extended-duration enoxaparin reduced VTE incidence compared with placebo (2.5% vs. 4%; absolute risk difference favoring enoxaparin, -1.53% [95.8% CI, -2.54% to -0.52%]). Enoxaparin increased major bleeding events (0.8% vs. 0.3%; absolute risk difference favoring placebo, 0.51% [95% CI, 0.12% to 0.89%]). The benefits of extended-duration enoxaparin seemed to be restricted to women, patients older than 75 years, and those with level 1 immobility. LIMITATION: Estimates of efficacy and safety for the overall trial population are difficult to interpret because of the change in eligibility criteria during the trial. CONCLUSION: Use of extended-duration enoxaparin reduces VTE more than it increases major bleeding events in acutely ill medical patients with level 1 immobility, those older than 75 years, and women

Low-dose vs high-dose paclitaxel-coated balloons for femoropopliteal lesions: 2-Year results from the COMPARE Trial.

Background: So far only 1-year data have been reported for direct comparisons of paclitaxel-coated balloons (PCBs) using different coating technologies. Objectives: The aim of this study was to report the 24-month results on the efficacy and safety of low-dose vs high-dose PCBs with nominal paclitaxel densities of 2.0 and 3.5 μg/mm2 and different coating technologies for femoropopliteal interventions from the COMPARE (Compare I Pilot Study for the Treatment of Subjects With Symptomatic Femoropopliteal Artery Disease) trial. Procedural characteristics of clinically driven (CD) target lesion revascularization (TLR) were analyzed. Methods: Within a prospective, multicenter, clinical trial, 414 patients with symptomatic femoropopliteal lesions (Rutherford categories 2-4, maximum lesion length 30 cm) were randomly assigned in a 1:1 ratio to endovascular treatment with either a low-dose (Ranger) or a high-dose (IN.PACT) PCB after stratification for lesion length. Two-year follow-up included assessment of primary patency (defined as absence of CD TLR or binary restenosis with a peak systolic velocity ratio >2.4 by duplex ultrasound), safety, and functional and clinical outcomes. Results: At 2 years, the Kaplan-Meier estimates of primary patency were 70.6% and 71.4% for the low-dose and high-dose PCBs (log-rank P = 0.96), respectively. One major amputation occurred in the high-dose group, and rates of all-cause mortality (3.6% vs 2.2%; P = 0.55) and CD TLR (17.3% vs 13.0%; P = 0.31) were similar between the groups. Among a total of 57 CD TLRs, 44.6% were performed for reocclusion and 28.1% for in-stent restenosis. Functional and clinical benefits over baseline were sustained in both groups. Conclusions: The 2-year results of the COMPARE trial demonstrate a sustained treatment benefit of both low-dose and high-dose PCBs for femoropopliteal interventions including a wide range of lesion lengths. (Compare I Pilot Study for the Treatment of Subjects With Symptomatic Femoropopliteal Artery Disease; NCT02701543

Postthrombotic syndrome and quality of life after deep vein thrombosis in patients treated with edoxaban versus warfarin

International audienceBackground Postthrombotic syndrome (PTS) is a long-term complication after deep vein thrombosis (DVT) and can affect quality of life (QoL). Pathogenesis is not fully understood but inadequate anticoagulant therapy with vitamin K antagonists is a known risk factor for the development of PTS. Objectives To compare the prevalence of PTS after acute DVT and the long-term QoL following DVT between patients treated with edoxaban or warfarin. Methods We performed a long-term follow-up study in a subset of patients with DVT who participated in the Hokusai-VTE trial between 2010 and 2012 (NCT00986154). Primary outcome was the prevalence of PTS, defined by the Villalta score. The secondary outcome was QoL, assessed by validated disease-specific (VEINES-QOL) and generic health-related (SF-36) questionnaires. Results Between 2017 and 2020, 316 patients were enrolled in 26 centers in eight countries, of which 168 (53%) patients had been assigned to edoxaban and 148 (47%) to warfarin during the Hokusai-VTE trial. Clinical, demographic, and thrombus-specific characteristics were comparable for both groups. Mean (SD) time since randomization in the Hokusai-VTE trial was 7.0 (1.0) years. PTS was diagnosed in 85 (51%) patients treated with edoxaban and 62 (42%) patients treated with warfarin (adjusted odds ratio 1.6, 95% CI 1.0-2.6). Mean differences in QoL scores between treatment groups were not clinically relevant. Conclusion Contrary to our hypothesis, the prevalence of PTS tended to be higher in patients treated with edoxaban compared with warfarin. No differences in QoL were observed. Further research is warranted to unravel the role of anticoagulant therapy on development of PTS

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)