Beruflich Dokumente
Kultur Dokumente
Alessandro Pezzini, MD
Mario Grassi, PhD
Maurizio Paciaroni, MD
Andrea Zini, MD
Giorgio Silvestrelli, MD,
PhD
Elisabetta Del Zotto,
MD, PhD
Valeria Caso, MD, PhD
Maria Luisa DellAcqua,
MD
Alessia Giossi, MD
Irene Volonghi, MD
Anna Maria Simone, MD
Alessia Lanari, MD, PhD
Paolo Costa, MD
Loris Poli, MD
Andrea Morotti, MD
Valeria De Giuli, MD
Daniele Pepe, PhD
Massimo Gamba, MD
Alfonso Ciccone, MD
Marco Ritelli, PhD
Marina Colombi, PhD
Giancarlo Agnelli, MD,
PhD
Alessandro Padovani,
MD, PhD
On behalf of the
Multicenter Study on
Cerebral Hemorrhage
in Italy (MUCH-Italy)
Investigators
Correspondence to
Dr. Pezzini:
ale_pezzini@hotmail.com or
alessandro.pezzini@med.unibs.it
Supplemental data at
www.neurology.org
ABSTRACT
Objective: To test the hypothesis that the effect of antithrombotic medications on the risk of intracerebral hemorrhage (ICH) varies according to the location of the hematoma.
Methods: Consecutive patients with ICH were enrolled as part of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy). Multivariable logistic regression models served to examine
whether risk factors for ICH and location of the hematoma (deep vs lobar) predict treatmentspecific ICH subgroups (antiplatelets-related ICH and oral anticoagulants [OACs]related ICH).
Results: A total of 870 (313 lobar ICH, 557 deep ICH) subjects were included. Of these, 223
(25.6%) were taking antiplatelets and 77 (8.8%) OACs at the time of stroke. The odds of
antiplatelet-related ICH increased with aging (odds ratio [OR] 1.05; 95% confidence interval
[CI] 1.031.07) and hypertension (OR 1.86; 95% CI 1.222.85) but had no relation with the
anatomical location of ICH. Conversely, lobar location of the hematoma was associated with the
subgroup of OAC-related ICH (OR 1.70; 95% CI 1.032.81) when compared to the subgroup of
patients taking no antithrombotic medications. Within the subgroup of patients taking OACs,
international normalized ratio (INR) values were higher in those with lobar ICH as compared to
those with deep ICH (2.8 6 1.1 vs 2.2 6 0.8; p 5 0.011). The proportion of patients with lobar
hematoma increased with increasing intensity of anticoagulation, with a ;2-fold increased odds
of lobar compared to deep ICH (odds 2.17; p 5 0.03) in those exposed to overanticoagulation
(INR values .3.0).
Antithrombotic medications are a highly effective therapy for the prevention of thromboembolic
strokes in common clinical situations. However, the increasing use of both antiplatelet and oral
anticoagulant (OAC) agents in an aging population has been associated with an increased risk of
intracerebral hemorrhage (ICH),14 with the annual incidence ranging from 0.02% to 0.47% in
patients taking a single antiplatelet agent to 0.3%0.6% in those on OAC therapy.5,6 The
prevention of ICH in patients with antithrombotic medications is therefore critical, and the
identification of risk factors for bleeding is an important practical issue. Data are needed to
determine how specific markers may contribute to individualized risk prediction in order to
make antithrombotics as safe and effective as possible. Several lines of evidence support the
hypothesis that age-related disorders of cerebral small vessels are closely linked to this rare but
devastating complication of antithrombotics use. In other terms, antithrombotic medications
From the Dipartimento di Scienze Cliniche e Sperimentali, Clinica Neurologica (A. Pezzini, P.C., L.P., A.M., V.D.G., A. Padovani), and Divisione
di Biologia e Genetica, Dipartimento di Medicina Molecolare e Traslazionale (M.R., M.C.), Universit degli Studi di Brescia; Dipartimento di
Scienze del Sistema Nervoso e del Comportamento (M. Grassi, D.P.), Unit di Statistica Medica e Genomica, Universit di Pavia; Stroke Unit and
Divisione di Medicina Cardiovascolare (M.P., V.C., G.A.), Universit di Perugia; Stroke Unit (A.Z., M.L.D., A.M.S.), Clinica Neurologica, Nuovo
Ospedale Civile S. Agostino Estense, AUSL Modena; U.O di Neurologia (G.S., A.L., A.C.), Ospedale C. Poma, Mantova; U.O. di Recupero e
Rieducazione Funzionale (E.D.Z.), IRCCS Fondazione Don Gnocchi, Rovato; U.O Neurologia (A.G., I.V.), Istituto Clinico S. Anna, Brescia;
and Stroke Unit (M. Gamba), Neurologia Vascolare, Spedali Civili di Brescia, Brescia, Italy.
Coinvestigators are listed on the Neurology Web site at www.neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
2014 American Academy of Neurology
Neurology 82
Table 1
Antiplatelet-related
ICH (n 5 223)
OAC-related ICH
(n 5 77)
Age, y, mean 6 SD
69.8 6 13.9
77.2 6 9.5
78.1 6 8.8
Female
239 (41.9)
111 (49.8)
35 (45.5)
0.132
BMI 30 kg/m2
202 (35.8)
72 (32.3)
25 (32.5)
0.592
48 (8.5)
69 (31.1)
16 (20.8)
,0.001
Brain ischemia
20 (3.5)
44 (19.8)
17 (22.1)
,0.001
Atrial fibrillation
20 (3.5)
48 (21.6)
50 (66.7)
,0.001
13 (2.3)
5 (2.2)
6 (7.8)
Nonhypertensive
152 (26.8)
34 (15.2)
16 (20.8)
Hypertensive on treatment
299 (52.7)
172 (77.1)
52 (67.5)
116 (20.5)
17 (7.6)
9 (11.7)
Hypertension
p Value
0.002
0.019
,0.001
Diabetes
0.642
Nondiabetic
470 (82.9)
Diabetic on treatment
69 (12.2)
32 (14.3)
12 (15.6)
28 (4.9)
11 (4.9)
6 (7.8)
180 (80.7)
59 (76.6)
Cholesterolemia
0.012
Nonhypercholesterolemic
455 (80.2)
171 (76.7)
66 (85.7)
Hypercholesterolemic on treatment
with statins
51 (9.0)
36 (16.1)
9 (11.7)
59 (10.4)
16 (7.2)
2 (2.6)
Current smoking
83 (14.7)
28 (12.6)
5 (6.5)
0.128
93 (16.3)
30 (13.5)
11 (14.3)
0.580
Deep
377 (66.1)
139 (62.3)
41 (53.2)
0.072
Lobar
193 (33.9)
84 (37.7)
36 (46.8)
ICH location
Abbreviations: BMI 5 body mass index; ICH 5 intracerebral hemorrhage; OAC 5 oral anticoagulant.
Data are n (%) unless otherwise noted.
Figure 1
Within the subgroup of oral anticoagulantrelated intracerebral hemorrhage. INR 5 international normalized ratio.
Table 2
Oral anticoagulant
related ICHs vs nonantithrombotic-related
ICHs
Model 1
OR
95% CI
OR
95% CI
1.05
1.031.07
1.06
1.031.09
Hypertension
1.86
1.222.85
1.31
0.722.38
1.17
0.831.64
1.70
1.032.81
Neurology 82
Figure 2
Relation between anatomical location of the hematoma and international normalized ratio values
(A) Percentage of international normalized ratio (INR) values conditional to the location of the hematoma. (B) Percentage of
lobar and deep intracerebral hemorrhages (ICHs) conditional to INR values. (C) 4 3 2 frequency table of lobar/deep ICH by
INR values with odds ratio (OR), 95% confidence interval (CI), and p values for lobar/deep.
Neurology 82
Dr. Morotti, Dr. De Giuli, Dr. Ciccone, Dr. Ritelli, Dr. Colombi,
Dr. Agnelli: manuscript drafting/revising, data acquisition. Dr. Padovani:
manuscript drafting/revising, study design, study supervision.
STUDY FUNDING
No targeted funding reported.
DISCLOSURE
The authors report no disclosures relevant to the manuscript. Go to
Neurology.org for full disclosures.
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