MD Conference Express AHA 2013 - (Page 37)
trial, the rates of International Society on Thrombosis and
Haemostasis major bleeding and ICH were significantly
lower with apixaban compared with warfarin [Granger CB
et al. N Engl J Med 2011].
Table 1. Six-Month Event Rates in Warfarin-Treated Patients
With Stable INR
Characteristic
Comparator
Stable group, group,
n=2504
n=3569
p Value
Received heparin, %*
0.3
3.2
<0.001
Deceased, n (%)
10 (0.4)
58 (1.6)
<0.001
AC-related death, n (%)
1 (0.04)
5 (0.1)
0.411†
AC-related thrombosis,
n (%)
10 (0.4)
26 (0.7)
0.100
AC-related bleeding,
n (%)
19 (0.8)
101 (2.8)
<0.001
AC-related bleeding or
thrombosis, n (%)
28 (1.1)
127 (3.6)
<0.001
AC=anticoagulation.
*Heparin or low-molecular-weight heparin; †Fisher exact test.
Table 2. Safety Outcomes With Rivaroxaban
Rivaroxaban Warfarin
Event Rate or Event Rate
N (Rate)
or N (Rate)
HR
p Value
Major
3.6
3.4
1.04
0.58
>2 g/dL Hg drop
2.8
2.3
1.22
0.02
Transfusion
(> 2 units)
1.6
1.3
1.25
0.04
Critical organ
bleeding
0.8
1.2
0.69
0.007
Bleeding causing
death
0.2
0.5
0.50
0.003
Intracranial
hemorrhage
55 (0.5)
84 (0.7)
0.67
0.02
Hg=hemoglobin.
Left atrial appendage (LAA) closure is an option to
prevent stroke in patients at high risk of stroke in whom
long-term anticoagulation is contraindicated or in whom
INR control cannot be achieved, said Amin Al-Ahmad, MD,
Texas Cardiac Arrhythmia Institute, Austin, Texas, USA.
Endocardial approaches to close the LAA are the
Watchman LAA System and Coherex Medical. The
Watchman, not currently approved in the United States, is
a self-expanding nitrol frame structure with fixation barbs
that engage the LAA wall when the delivery catheter is
employed. In a randomized clinical trial of 707 AF patients
[Holmes DR. Lancet 2009], the Watchman was found to be
noninferior to warfarin on the primary efficacy endpoint
(a composite of stroke, cardiovascular death, or systemic
embolism). Periprocedural complications including
cardiac perforation, pericardial effusion with tamponade,
and device embolization occurred in 6% to 8% of patients.
The Coherex WaveCrest System, also not currently approved
in the United States, comes in three sizes to accommodate
different ostial diameters, and can be used in a wide variety
of LAA anatomies.
Potential issues with endocardial approaches are
incomplete closure, thrombus formation at follow-up,
and an inability to retrieve the device if deployment
is suboptimal.
Measurement and monitoring of the anticoagulant
effects of new OACs, although not required routinely
because of their predictable pharmacokinetics and a wide
therapeutic window, may be useful in some situations,
such as in patients with bleeding or at risk of bleeding or
thromboembolism, said Graeme J. Hankey, MD, University
of Western Australia, Perth, Australia.
Antifactor Xa assays accurately measure the effects of
the oral factor Xa inhibitors apixaban and rivaroxaban,
depending on the calibrator [Doufils J et al. Thromb
Haemost 2013; Thromb Res 2012]. When interpreting the
Hemoclot assay for dabigatran, or the antifactor Xa assay
for Xa inhibitors, the timing of the last tablet and the
timing of the blood test must be known in order to get an
idea of whether the blood concentration should be rising,
plateauing, or falling [Mani H et al. J Thromb Thrombolysis
2013], said Prof. Hankey.
The other important laboratory test is creatinine
clearance. A residual anticoagulant effect is unlikely if renal
function is normal and it has been ≥24 hours since the
last dose of OAC. A widely and rapidly available assay that
correlates with a validated therapeutic window is awaited.
Specific antidotes to the new OACs are still under
development. A monoclonal antibody against dabigatran
(aDabi-Fab) has shown rapid reversal of the anticoagulant
effect in ex vivo clotting assays in a rat model [Schiele
F et al. Blood 2013]. A recombinant protein, r-antidote
(PRT064445), to Xa inhibitors reversed the anticoagulant
effects of these agents in a rat model [Lu G et al. Nat Med
2013]. Another potential antidote to Xa inhibitors is
andexanet alfa, which has shown rapid and near complete
reversal of apixaban's anticoagulant effect [http://
investors.portola.com/phoenix.zhtml?c=198136&p=irolnewsArticle&ID=1883157&highlight=]. PER 977 is a
synthetic small molecule that acts as a universal reversal
agent [Laulicht B et al. Circulation (abstr 11395)].
In the past 5 years there have been many new
developments in the management of AF. Additional
information from studies of novel therapeutics will
continue to help optimize therapy and reduce the risk of
stroke or systemic embolization while minimizing bleeding
for patients with AF.
Official Peer-Reviewed Highlights From the American Heart Association Scientific Sessions 2013
37
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