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
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