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5. Alexander, J. H. et al. Apixaban with antiplatelet
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NEJMoa1112277.
7. Tricoci, P. et al. Thrombin-receptor antagonist
vorapaxar in acute coronary syndromes.
ATRIAL FIBRILLATION IN 2011
Stroke prevention in AF
Gregory Y. H. Lip
In 2011, key trials with oral factor Xa inhibitors in patients with atrial
fibrillation highlighted promising data on these novel anticoagulants.
Patients with ≥1 stroke risk factors can be considered for oral
anticoagulation. These novel, fixed-dose drugs are given without
monitoring, so clinicians must learn to balance stroke and bleeding risks.
Lip, G. Y. H. Nat. Rev. Cardiol. 9, 71–73 (2012); published online 20 December 2011;
doi:10.1038/nrcardio.2011.203
The year 2011 saw the publication of three
pivotal phase III trials for two oral direct
factor Xa inhibitors, apixaban and rivaroxaban,
1–3 as well as important articles on bleeding
risk assessment 4 and the net clinical
benefit of thromboprophylaxis. 5 Novel oral
anticoagulants that are viable alternatives to
warfarin have clearly changed the landscape
of stroke prevention in patients with atrial
fibrillation (AF). 6 Until recently, the recommended
approach was artificially to stratify
patients with AF into low, intermediate, and
high risk strata—despite stroke risk being a
continuum—so that those classed as being
at high risk could be targeted for an inconvenient
(and potentially dangerous) drug,
warfarin. Many studies, however, have shown
that the categorization of patients into low,
intermediate, or high risk strata has poor
correlation with actual warfarin prescribing,
and that the predictive value of risk
schemes such as the CHADS 2 score (Box 1)
to identify high-risk patients is suboptimal. 7
Consequently, guidelines now recommended
the use of the CHA 2 DS 2 -VASc score (Box 1)
to complement the older (but simpler)
CHADS 2 score.
Indeed, emphasis is now directed towards
identification of ‘truly low-risk’ patients with
AF by being more inclusive (rather than
exclusive) of common risk factors for stroke,
because these patients might not need any
antithrombotic therapy. Meanwhile, patients
with ≥1 risk factor for stroke should be considered
for effective stroke prevention with
oral anticoagulation, whether with (very)
well-controlled warfarin or one of the
N. Engl. J. Med. http://dx.doi.org/10.1056/
NEJMoa1109719.
8. Mathews, R. et al. In-hospital major
bleeding during ST-elevation and
non-ST-elevation myocardial infarction care:
derivation and validation of a model from
the ACTION Registry®-GWTG.
Am. J. Cardiol. 107, 1136–1143
(2011).
novel agents, either an oral direct thrombin
inhibitor (such as dabigatran) or an
oral direct factor Xa inhibitor (for example,
rivaroxaban or apixaban). 1 Indeed, the
CHA 2 DS 2 -VASc score has consistently been
shown to outperform the CHADS 2 score
in identification of truly low-risk patients
and is as good as—and possibly better
than—the CHADS 2 score in the identification
of high-risk patients who subsequently
suffer thromboembolism. 7,8
Key advances
■ In the AVERROES trial, apixaban was
superior to aspirin for stroke prevention
in patients with atrial fibrillation (AF),
with similar rates of major bleeding and
improved tolerability 1
■ In the ARISTOTLE trial, apixaban was
superior to warfarin for prevention of
stroke and systemic embolism in patients
with AF, with significantly less major
bleeding and improved survival 2
■ In the ROCKET-AF trial, rivaroxaban was
noninferior to warfarin for stroke prevention
in a high-risk population of patients with
AF, with similar rates of major bleeding 3
■ The HAS-BLED score is well validated
to predict major-bleeding events in
patients receiving anticoagulation therapy,
and outperforms other bleeding risk
assessment schemes 4
■ ‘Truly low-risk’ patients with a
CHA 2 DS 2 -VASc score of 0 do not
require thromboprophylaxis; net clinical
benefit is greatest in patients with a high
HAS-BLED score, where reduced ischemicstroke
risk outweighs the increased
intracranial-bleeding risk 5
CARDIOLOGY
Attention has also been directed to assessment
of bleeding risk. Common risk factors
for bleeding (as well as potentially correctable
risk factors, such as uncontrolled blood pressure
and concomitant aspirin use in patients
receiving anticoagulation therapy) can
inform clinical decision- making, especially
with the novel oral anticoagulants that can
come in high-dose and low-dose regimens. 9
Investigators in the AVERROES trial 1
studied 5,599 patients with AF and ≥1 risk
factor for stroke, and who had refused warfarin
or been deemed unsuitable for war farin
by the investigators on the basis of the inclusion
criteria. The trial was stopped early
because of the clear superiority of apixaban
over aspirin, with a 55% reduction in the
primary end point of stroke and systemic
embolism (HR 0.45, 95% CI 0.32–0.62,
P