Although the risk of thromboembolism in patients off anticoagulation is higher than the overall risk of ICH recur-rence, there is a marked paucity of prospective large population-based d
Trang 1Carlos A Molina and Magdy H Selim
Evidence Facing Big Fears The Dilemma of Resuming Anticoagulation After Intracranial Hemorrhage : Little
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doi: 10.1161/STROKEAHA.111.631689 2011;42:3665-3666; originally published online November 3, 2011;
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Trang 2The Dilemma of Resuming Anticoagulation After
Intracranial Hemorrhage
Little Evidence Facing Big Fears
Carlos A Molina, MD, PhD; Magdy H Selim, MD, PhD
Intracranial hemorrhage (ICH) is the most feared and
devastating complication of anticoagulant treatment,
lead-ing to death or disability in two thirds of cases Once ICH
occurs, the decision of whether to resume anticoagulation is a
true therapeutic dilemma that requires balancing the
compet-ing risks of hematoma growth or recurrent ICH and disablcompet-ing
thromboembolic events
Although the risk of thromboembolism in patients off
anticoagulation is higher than the overall risk of ICH
recur-rence, there is a marked paucity of prospective large
population-based data on the real risk of ICH recurrence on
warfarin The lack of randomized controlled trials probably
reflects the ethical challenge of prescribing patients a
medi-cation to which they have an apparent contraindimedi-cation
Therefore, in clinical practice, the risk is usually, and
inap-propriately, extrapolated from the overall risk of major
bleeding on warfarin (approximately 3%), in which older age
and elevated international normalized ratio are factors
asso-ciated with an increased risk
The little evidence available on resuming oral
anticoagu-lation after ICH comes from either expert opinions or few
nonrandomized mainly retrospective studies.1,2These studies
included highly selected high-risk patients and showed
non-conclusive and even discrepant results This limited and weak
evidence along with our own experience and common sense
are the weapons that our protagonists use for facing the
physicians’ fears and uncertainties of increasing the risk of a
devastating recurrent ICH or leaving the patient unprotected
from thromboembolic complications Dr Shulman’s argument
is based on the high risk of recurrent ICH on warfarin after
ICH at any location and gives a broad recommendation of
abstaining from resuming warfarin He argues that in our
case, warfarin should not be resumed because the risk of
recurrent ICH (15%) is more than twice as high as the risk of
ischemic stroke (6%) Dr Steiner delineates a more restrictive
scenario, in which the risk of thromboembolism outweighs
the risk of ICH recurrence in a hypertensive-related, nonlobar
ICH He recommends that warfarin should be restarted if
blood pressure and other risk factors are adequately controlled
Among all factors associated with an increased risk of recurrent ICH on warfarin, ICH location and documented history of thromboembolism seem to be the key factors that tilt the risk/benefit balance of restarting anticoagulation after ICH In 1 of the only 2 published epidemiological studies, the risk of recurrent ICH on warfarin was⬎5-fold higher in lobar compared with deep ICH, although the rate of survival among patients with deep ICH was low The topographical location
of ICH may reflect the underlying microvascular pathology Lobar ICH in the aged population is associated with cerebral amyloid angiopathy and an inherent high risk of recurrence Deep ICH is often hypertension-related Although improved management of hypertension can reduce the risk of recurrent deep ICH, there is limited room for improving management
in lobar ICH if blood pressure is well controlled On the other hand, in an analysis of 52 patients, thromboembolic events occurred in 48% of patients in whom warfarin was not restarted, all of them were being treated for a previous event, suggesting that secondary rather than primary prevention is a stronger indication for resuming anticoagulation.2
The dilemma of restarting oral anticoagulation in the long-term management of ICH may be better addressed by considering other factors, including the underlying reason for which the patient was originally started on anticoagulation, difficulties in controlling the international normalized ratio, the risk of thromboembolic stroke based on the CHADS2 score, and the presence and extent of microbleeds on gradient-echo MRI Deep ICH, secondary prevention, high CHADS2 score, mechanical valve, or hypercoagulable state are factors arguing in favor of resumption of anticoagulation Conversely, lobar ICH, presence of multiple microbleeds on MRI, low CHADS2 score, and difficulties controlling inter-national normalized ratio configure an unfavorable risk/ benefit profile In addition to these factors, the decision of whether to resume anticoagulation must take into consider-ation the underlying cause of ICH For example, treatable
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association This article is Part 3 of a 3-part article Parts 1 and 2 appear on pages 3661 and 3663, respectively.
Received August 1, 2011; accepted August 8, 2011.
From Hospital Valld’Hebron-Barcelona (C.A.M.), Barcelona, Spain; and the Stroke Division (M.H.S.), Beth Israel Deaconess Medical Center, Boston, MA Correspondence to Carlos A Molina, MD, PhD, Stroke Unit, Department of Neurosciences, Hospital Valld’Hebron-Barcelona, Passeig Vall d’Hebron 119-129, 08035, Barcelona, Spain E-mail cmolina@vhebron.net; and Magdy H Selim, MD, PhD, Beth Israel Deaconess Medical Center, Stroke Division, 330 Brookline Avenue, Palmer 127, Boston, MA 02215 E-mail mselim@bidmc.harvard.edu
(Stroke 2011;42:3665-3666.)
© 2011 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.111.631689
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Trang 3secondary causes of ICH such as an arteriovenous
malforma-tion, in which concomitant use of anticoagulation is only
guilty by association, may not pose a risk for ICH recurrence
once treated; and traumatic ICH in the setting of
anticoagu-lant use does not necessarily imply increased risk for ICH
recurrence
The optimal timing for resumption of anticoagulation after
ICH is unresolved In the acute phase, the risk of continuous
bleeding from restarting anticoagulation exceeds the risk of
thromboembolism from withholding it Later on, the risk of
stroke and systemic embolism in the absence of
anticoagula-tion outweighs that of rebleeding Therefore, both the
Amer-ican Heart Association and the European Stroke Initiative
recommend that in patients with high risk of
thromboembo-lism, anticoagulation should be restarted between 7 and 10
days Dr Shulman and his colleagues, however, questioned
these recommendations and suggested that the optimal time
for resumption of anticoagulation is after 10 weeks Clearly,
the timing depends on the indication for anticoagulation and
the patient’s comorbidities
In patients with atrial fibrillation and an unfavorable
risk/benefit profile to restarting anticoagulation, antiplatelet
therapy is a reasonable alternative In some, the use of a left
atrial appendage occlusion device or procedure may be
another consideration Although dabigatran has demonstrated
fewer bleeding complications in patients with atrial fibrilla-tion, compared with warfarin, safety and efficacy data in patients with ICH is lacking
The current dilemma is likely to persist despite ongoing efforts to develop decision-support tools given the heteroge-neity of the underlying causes of anticoagulation-related ICH and patient populations It exemplifies the fact that medicine
is an art and that the decision of whether and when to resume anticoagulation after ICH should be made on an individual case-by-case basis after taking into considerations the pa-tient’s risk factors for thromboembolism and his or her preferences after a thorough discussion of the risks versus benefits
Disclosures
None.
References
1 De Vleeschouwer S, Van Calenbergh F, van Loon J, Nuttin B, Goffin J, Plets C Risk analysis of thromboembolic and recurrent bleeding events in the management of intracranial hemorrhage due to oral anticoagulation.
Arch Chir Belg 2005;105:268 –274.
2 Classen DO, Kazemi N, Zubkov AY, Wijdicks EF, Rabinstein AA Restarting anticoagulation therapy after warfarin-associated intracranial
hemorrhage Arch Neurol 2008;65:1313–1318.
K EY W ORDS : acute stroke 䡲 hemorrah 䡲 intracranial stenosis
3666 Stroke December 2011
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