Increased benefit of betrixaban among patients with a history of venous thromboembolism: a post-hoc analysis of the APEX trial.

Hospitalized acute medically ill patients with a history of venous thromboembolism (VTE) are at increased risk for recurrent VTE. We characterized the efficacy and safety of betrixaban for prevention of recurrent VTE in these high risk patients. The APEX trial randomized 7513 acutely ill hospitalized medical patients at risk for developing VTE to receive either betrixaban for 35-42 days or enoxaparin for 10 ± 4 days to prevent VTE. This exploratory post-hoc analysis assessed the efficacy and safety of betrixaban versus enoxaparin among subjects with and without prior VTE. Time-to-multiple symptomatic VTE events was also calculated. Approximately 8% of subjects in both arms had prior VTE, which was associated with a fourfold increase in adjusted risk of VTE [MV OR 4.03, 95% CI 3.06-5.30, p < 0.001]. Betrixaban reduced VTE compared with enoxaparin among subjects with prior VTE [32 (10.4%) vs. 55 (18.9%), RR 0.57, 95% CI 0.38-0.86, p = 0.006, ARR 8.5%, NNT 12] and without prior VTE [133 (3.9%) vs. 168 (4.9%), RR 0.79, 95% CI 0.64-0.99, p = 0.042, ARR 1.0%, NNT 100] (interaction p > 0.05). Additionally, four subjects in the enoxaparin arm and one subject in the betrixaban arm experienced a recurrent VTE. Compared with enoxaparin, betrixaban use was associated with reduction of recurrent VTE events through the active treatment period [36 vs. 57, HR 0.63, 95% CI 0.41-0.97, p = 0.045] and through the end of study [38 vs. 71, HR 0.54, 95% CI 0.36-0.81, p = 0.004]. Prior VTE is associated with a fourfold increase in the risk of VTE among hospitalized medically ill patients. Only 12 such patients would need to be treated with betrixaban versus enoxaparin to prevent an additional VTE endpoint. Betrixaban reduced not only the first but also all recurrent VTE events in a time-to-any-event analysis. TRIAL REGISTRATION: http://www.clinicaltrials.gov , Unique identifier: NCT01583218.

Changes in Care for Acute Pulmonary Embolism Through A Multidisciplinary Pulmonary Embolism Response Team.

BACKGROUND: Optimal management of acute pulmonary embolism requires expertise offered by multiple subspecialties. As such, pulmonary embolism response teams (PERTs) have increased in prevalence, but the institutional consequences of a PERT are unclear. METHODS: We compared all patients that presented to our institution with an acute pulmonary embolism in the 3 years prior to and 3 years after the formation of our PERT. The primary outcome was in-hospital pulmonary embolism-related mortality before and after the formation of the PERT. Sub-analyses were performed among patients with elevated-risk pulmonary embolism. RESULTS: Between August 2012 and August 2018, 2042 patients were hospitalized at our institution with acute pulmonary embolism, 884 (41.3%) pre-PERT implementation and 1158 (56.7%) post-PERT implementation, of which 165 (14.2%) were evaluated by the PERT. There was no difference in pulmonary embolism-related mortality between the two time periods (2.6% pre-PERT implementation vs 2.9% post-PERT implementation, P = .89). There was increased risk stratification assessment by measurement of cardiac biomarkers and echocardiograms post-PERT implementation. Overall utilization of advanced therapy was similar between groups (5.4% pre-PERT implementation vs 5.4% post-PERT implementation, P = 1.0), with decreased use of systemic thrombolysis (3.8% pre-PERT implementation vs 2.1% post-PERT implementation, P = 0.02) and increased catheter-directed therapy (1.3% pre-PERT implementation vs 3.3% post-PERT implementation, P = 0.05) post-PERT implementation. Inferior vena cava filter use decreased after PERT implementation (10.7% pre-PERT implementation vs 6.9% post-PERT implementation, P = 0.002). Findings were similar when analyzing elevated-risk patients. CONCLUSION: Pulmonary embolism response teams may increase risk stratification assessment and alter application of advanced therapies, but a mortality benefit was not identified.

Coenzyme Q10 in the Treatment of Corneal Edema in Kearns-Sayre: Is There an Application in Fuchs Endothelial Corneal Dystrophy?

PURPOSE: Corneal involvement in mitochondrial disease is seldom described. Kearns-Sayre syndrome (KSS) is a mitochondrial disorder characterized by retinitis pigmentosa, external ophthalmoplegia, and heart block. We report 2 patients with KSS with corneal lesions involving the endothelium, which improved with Coenzyme Q10 (CoQ10). Based on recent research regarding the role of dysfunctional oxidative metabolism in Fuchs Endothelial Corneal Dystrophy (FECD), we propose that mitochondrial diseases and FECD share a final pathway. METHODS: A chart review was performed and a review of the literature was completed with a PubMed search using the terms "Kearns-Sayre Syndrome", "mitochondria", "endothelium", "Fuchs endothelial corneal dystrophy", and "cornea". RESULTS: There are 19 reports of corneal involvement in clinical phenotypes of mitochondrial disease. Nine of these 19 cases had findings consistent with KSS. Our patients with KSS had microcystic changes throughout the cornea and excrescences on the endothelial surface seen with ultrasound biomicroscopy, similar to the clinical findings in FECD. CoQ10 improved corneal disease in both children. CoQ10 deficiency has been reported in a variety of mitochondrial diseases, and efficacy of supplementation has been demonstrated. It may be beneficial in these patients because of its antioxidant properties and role in oxidative phosphorylation. CONCLUSIONS: The common deletion found in patients with KSS has recently been implicated in FECD, which has recently been shown to be a disease related to dysfunctional oxidative metabolism. Future research should explore the use of antioxidants, such as CoQ10 in patients with FECD.