MD Conference Express ATS 2013 - (Page 25)

Although current American College of Chest Physicians guidelines state that IVC filters should not be used in addition to anticoagulation, they are recommended for patients in whom anticoagulation is contraindicated. If an IVC filter is inserted as an alternative to anticoagulation, it should be followed by a conventional course of anticoagulant therapy if the risk of bleeding resolves [Kearon C et al. Chest 2012]. The American Heart Association guidelines are similar in that they recommend the use of IVC filters in patients with a contraindication to anticoagulation and in the case of failure of anticoagulation. IVC filters may also be considered for patients with very poor cardiopulmonary reserve but should not be routinely used as an adjunct to anticoagulation or lysis [Jaffe MR et al. Circulation 2011]. Dr. Bull commented that while it is clear the IVC filters are appropriate when anticoagulation is not possible there remains a lack of good data for other scenarios such as in cases where anticoagulation has failed, in patients with poor cardiopulmonary reserve, as prophylaxis in highrisk patients and in the case of chronic thromboembolic pulmonary hypertension. The National Institute of Health is currently considering a study investigating the use of IVC filters in people with stable high and moderate risk for PE. David J. Kuter, MD, PhD, Massachusetts General Hospital, Boston, Massachusetts, USA, discussed how some of the new anticoagulants compare with older therapies such as warfarin and heparin. Unlike warfarin and heparin, which act at multiple sites in the coagulation cascade, some of the new anticoagulants act directly on thrombin either by irreversibly (lepirudin) or reversibly (bivalirudin) binding to the fibrinogen binding exosite and the active site pocket or by reversibly binding to only the active site (argatroban and dabigatran etexilate). Dabigatran etexilate is a twice-daily oral therapy with a long half-life (12 to 17 hours) that is cleared via the kidney (80%). Although not yet approved for this indication, dabigatran etexilate has been shown to be noninferior to warfarin in the management of DVT/PE, with a similar safety profile. Unlike warfarin, dabigatran does not require laboratory monitoring [Schulman S et al. N Engl J Med 2009]. Other new anticoagulants act on Factor Xa. Rivaroxaban is a once daily, oral direct inhibitor of Factor Xa, with a flat dose response curve, and a half-life of 5 to 9 hours. Clearance is via the kidneys (51%) [Kubitza D et al. Clin Pharmacol Ther 2005]. In most situations, rivaroxaban does not require monitoring. It is approved for the prophylaxis of DVT, which may go on to PE in patients undergoing hip or knee replacement surgery, to reduce the risk of stroke and systemic embolism in patients with non-valvularatrial fibrillation, and for the treatment of DVT/PE. It is noninferior to standard therapy for the treatment of PE and DVT with a potentially improved benefit–risk profile [EINSTEIN Investigators. N Engl J Med 2010; Einstein-PE Investigators. N Engl J Med 2012]. Apixiban is a twice-daily oral Factor Xa inhibitor that has mostly hepatic clearance (only 25% renal); though promising, it has not yet been approved for PE/DVT. Dr. Kuter noted that warfarin and heparin still work well, although heparin is probably more effective in acute situations because of its additional anticoagulation mechanism. He suggested considering the newer oral agents for stable patients who are ready for discharge to treat both the DVT and PE (Table 1). Table 1. Comparative Features of Warfarin and New Oral Anticoagulants Warfarin Dabigatran etexilate Rivaroxaban Apixaban Target Vit K epoxide reductase Thrombin Factor Xa Factor Xa Oral bioavailability 99% 6%-7% 60%-80% 80% T (max) 72-96 h 2h 2.5-4 h 3h Half-life 40 h 14-17 h 5-9 h healthy, 9-13 h elderly 8-15 h Monitoring INRadjusted Not needed Not needed Not needed Administration OD OD or BID QD or BID BID Metabolism/ elimination Cytochrome P450 80% renal, 20% biliary 66% renal, 33% biliary 25% renal, 75% biliary Antidote or treatment of bleeding Vitamin K + FFP, APCC, or recFVIIa Standard of care (dialysis, plasma or factor replacement; rVIIa) Standard of care (plasma or factor replacement; rVIIa; Xa derivative) Standard of care (plasma or factor replacement; rVIIa; Xa derivative) Assay PT/INR Ecarin clotting time Anti-factor Xa, Anti-factor Xa PiCT, HepTest Drug interactions CYP2C9, 1A2, and 3A4 Potent P-gp inhibitors/ inducers; PPIs decrease absorption Potent P-gp inhibitors/ inducers; CYP3A4 inhibitors Potent P-gp inhibitors/ inducers; CYP3A4 inhibitors Victor F. Tapson, MD, Duke University Medical Center, Durham, North Carolina, USA, discussed the practical use of biomarkers and scoring systems for patients with PE. All acute PE patients should be risk stratified, most importantly to determine who is at high risk for adverse events, and thus might benefit from escalation of therapy. However, despite the large body of research on biomarkers (ie, brain natriuretic peptide, troponin, and heart-type fatty acid binding protein), none, alone is sufficient for risk stratification, due to the limitations in the studies that have assessed them. These limitations include the absence of a standardized definition of RV dysfunction by echocardiogram, the lack of cardiac biomarker test standardization (different assays and thresholds for positive) and inadequate leg DVT assessment. Several scoring indices are available to support the data from the biomarkers but again none alone is sufficient. Standardized definitions and approaches are needed. Official Peer-Reviewed Highlights From the American Thoracic Society International Conference 2013 25

Table of Contents for the Digital Edition of MD Conference Express ATS 2013

MD Conference Express ATS 2013
Contents
Prevention and Early Treatment of Acute Lung Injury
Nocturnal Noninvasive Ventilation Improves Outcomes in Multiple Disorders
Hospital Readmissions: Challenges and Opportunities
EBUS-TBNA: Accurate and Safe for Detecting Sarcoidosis
Data Link Obstructive Sleep Apnea and Type 2 Diabetes
Statin Use Improves Respiratory-Related Mortality in Patients With COPD
Addition of Spironolactone to Ambrisentan May Be a Novel Treatment Strategy to Improve Outcome in Patients With PAH
Haloperidol Does Not Prevent Delirium in Ventilated ICU Patients
Beraprost Plus Sildenafil Effective in Pulmonary Arterial Hypertension
Dupilumab Is Safe and Effective for Controlling Asthma Attacks
Once-Daily QVA149 Improves Breathlessness in COPD Patients
CPAP in CVD and OSA Does Not Significantly Improve Cardiovascular Biomarkers
CPAP Reduces BP in Patients With Resistant Hypertension and Obstructive Sleep Apnea
Effects of Obesity on COPD
Pulmonary Embolism
Ventilator-Associated Pneumonia
Lung Cancer Screening
Idiopathic Pulmonary Fibrosis
Non-Small-Cell Lung Cancer

MD Conference Express ATS 2013

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