La fibrillazione
atriale ‘in rosa’
E’ proprio vero che
le donne rischiano
l’ictus più degli
uomini?
Paolo Verdecchia, F.A.C.C., F.E.S.C., F.A.H.A.
Hospital of Assisi
Department of Medicine
Via Valentin Müller, 1
06081 - Assisi PG
E-mail: [email protected]
Due ‘dogmi di fede’
1. Tra i pazienti con FA, il rischio di ictus
cerebrale è maggiore nelle donne
che negli uomini.
2. Se una donna ha CHA2DS2VASc = 1
(età < 65 anni e non vi sono altri
fattori di rischio), il rischio di ictus è
basso e non sono necessari farmaci
antitrombotici.
Nei pazienti con
fibrillazione atriale, il rischio
di ictus cerebrale è davvero
più alto nelle donne che
negli uomini?
The risk of stroke in AF patients
is higher in women than in men
1. Fang MC, Singer DE, Chang Y, Hylek EM, Henault LE, Jensvold NG, et al. Gender
differences in the risk of ischemic stroke and peripheral embolism in atrial
fibrillation: the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) study.
Circulation 2005;112:1687-91.
2. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk
stratification for predicting stroke and thromboembolism in atrial fibrillation using
a novel risk factor-based approach: the Euro heart survey on atrial fibrillation.
Chest 2010;137:263-72.
3. Hughes M, Lip GY. Stroke and thromboembolism in atrial fibrillation: a systematic
review of stroke risk factors, risk stratification schema and cost effectiveness data.
Thromb Haemost 2008;99:295-304.
4. Wang TJ, Massaro JM, Levy D, Vasan RS, Wolf PA, D’Agostino RB, et al. A risk
score for predicting stroke or death in individuals with new-onset atrial fibrillation
in the community: the Framingham Heart Study. JAMA 2003;290:1049-56.
5. Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW. Factors associated with
ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012
participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial
Fibrillation (SPAF) Investigators. Stroke 1999;30:1223-9.
6. Lane DA, Lip GY. Female gender is a risk factor for stroke and thromboembolism in
atrial fibrillation patients. Thromb Haemost 2009;101:802-5.
1. Female sex was also
associated with a higher
risk of fatal/disabling
stroke (HR1.8; p=0.03)
2. Estrogen hormone
replacement therapy in
women was associated
with higher risk of ischemic
stroke after adjustment for
other independent
associates (HR=3.2,
P=0.007).
Hart RG et al
Stroke. 1999;30:1223-1229
Lip GYH et al. Chest 2010;137:263-272
Female sex was an independent significant predictor of
stroke in three studies (range of individual RR 1.6 to
1.9), but not in three other studies.
The Stroke Risk in Atrial Fibrillation
Working Group. Neurology
2007;69:546–554
1. Five studies found
female sex to be a
significant
predictor for
stroke.
2. Five studies did
not find female sex
to be a significant
predictor for
stroke.
3. In one study, male
sex was a
significant
predictor for
stroke
Hughes et al
Thromb Haemost 2008; 99: 295–304
Hughes M et al. Thromb Haemost 2008;99:295-304
The case of new onset atrial fibrillation
Canadian Registry of Atrial Fibrillation (CARAF),
in subjects at their first ECG diagnosis of AF.
• Compared with men, women were older, more
likely to have symptoms, and with higher
heart rate during AF.
• Compared with older men, older women were
half as likely to receive warfarin and twice as
likely to receive ASA.
• Compared with men on warfarin, women on
warfarin were 3.35 times more likely to
experience a major bleed.
Humphries KH et al. Circulation. 2001;103:2365-2370
Not significant
trend
Humphries KH et al. Circulation. 2001;103:2365-2370
An ultimate
verdict from
Sweden ?
Participants. 100,802 patients with atrial fibrillation at
any Swedish hospital or hospital affiliated outpatient
clinic with a total follow-up of 139 504 years at risk
(median 1.2 years). Patients with warfarin at baseline,
mitral stenosis, previous valvular surgery, or who died
within 14 days from baseline were excluded.
Friberg et al. BMJ 2012; 344:e3522
Assessment of female sex as a risk factor
in atrial fibrillation in Sweden:
Nationwide Retrospective Cohort Study
Total population (global stroke rate 5.2%/year [7221 pts with stroke])
7
6
Absolute
rate
of
stroke
(x 100
subjects
per year)
5
Women vs men: HR 1.47 (1.40-1.54)
6.2
4
4.2
3
2
1
0
Women
Men
Friberg et al. BMJ 2012; 344:e3522
Men
Women
Age ≥ 75 y
Friberg et al. BMJ 2012; 344:e3522
Assessment of female sex as a risk factor
in atrial fibrillation in Sweden:
Nationwide Retrospective Cohort Study
Friberg et al. BMJ 2012; 344:e3522
In pazienti con FA, il
rischio di ictus è
maggiore nella
donna che nell’uono:
In donne senza pregressi
eventi tromboembolici o
ictus ischemico
In donne senza pregresso
infarto miocardico o
malattia vascolare
In donne con CHADS2
score da 0 a 3
Friberg et al. BMJ 2012; 344:e3522
Rifiniamo il paradigma….
Le donne sono a maggior rischio di ictus
cerebrale rispetto agli uomini quando sono:
- Di età tendenzialmente più avanzata (≥75
anni)
- A rischio tromboembolico non altissimo
(punteggio CHADS2 0-3)
- Senza precedente ictus, infarto
miocardico o altri eventi vascolari
Se una donna ha FA, ma la sua età
è inferiore ai 65 anni e non vi sono
altri fattori di rischio inclusi nel
punteggio CHA2DS2VASc, il rischio
di ictus ischemico è basso e non
sono necessari farmaci
antitrombotici
Friberg et al.
BMJ 2012; 344:e3522
Donna:
Età < 65 + 1 FR
Età > 65, non FR
Uomo:
1. Età > 75 anni, non FR
2. Età 65-74 + 1 FR
Uomo:
1. Età < 65 con 1 FR
2. Età 65-74, non FR
Stroke rate in
patients
with CHADS2
score 0-1
in relation to the
CHA2DS2VASc
score
Uomo:
1. Età < 65
senza FR
Donna:
1. età < 65
2. Non FR
Friberg et al.
BMJ 2012; 344:e3522
Stroke and Thromboembolism
in Patients Aged < 65 Years:
The CHA2DS2-VASc Risk Factors Excluding Age
Univariate
Multivariate
Risk Factor
HR (95% CI)
Interaction
with VKA[a]
HR (95% CI)
Interaction
with VKA[a]
Heart failure
2.16 (1.20–3.90)
.34
1.95 (1.04–3.66)
.48
Hypertension
1.40 (0.79–2.47)
.69
0.90 (0.49–1.66)
.98
Diabetes
2.42 (1.27–4.62)
.13
1.76 (0.86–3.59)
.08
Previous stroke
4.54 (2.37–8.71)
.34
5.66 (2.91–11.02)
.80
Vascular disease
2.49 (1.42–4.37)
.11
2.19 (1.22–3.92)
.17
Female sex
0.67 (0.33–1.33)
.24
0.70 (0.34–1.43)
.24
1. 6438 patients with NVAF in a four-hospital institution between 2000 and 2010.
2. Event rates of stroke/thromboembolism were calculated according to age category.
3. Independent risk factors of stroke and thromboembolism were investigated in Cox
regression models including patients with non-valvular AF aged < 65 years.
4. Among 6,438 patients with NVAF, 2,002 (31.1%) were aged < 65 years.
Olesen JB et al. Chest. 2012 Jan;141(1):147-53.
Conclusions
1. In AF patients, the risk of stroke is generally
higher in women than in men.
2. It is particularly higher in women at relatively
lower risk of stroke (CHADS2 score 0-3, without
previous stroke or myocardial infarction).
3. In male and female AF patients aged < 65 y
and without other RFs (CHA2DS2VASc = 0 in
men and 1 in women), the risk of stroke is low
in either gender and does not justify warfarin or
NOACs.
Atrial Fibrillation
Yes
Valvular Atrial Fibrillation
No
Yes
< 65 y and lone AF (including women)
No
Assess risk of stroke
(CHA2DS2VASc score)
0
1
≥2
Class I
Level A
Class IIa
Level A
Oral anticoagulant therapy
(either Vitamin k antagonists or NOA)
Best
option
No antithrombotic therapy
Class IIa
Level A
Novel anticoagulants
Camm AJ, Lip GY et al. ESC Guidelines 2012. Eur Heart J. 2012 Nov;33(21):2719-47
Alternative
option
Vitamin K antagonists
Grazie
per la vostra
attenzione