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 AssisiDepartment of MedicineVia Valentin Müller, 106081 - Assisi PGE-mail: verdec@tin.it

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 èbasso e non sono necessari farmaci antitrombotici.

Due ‘dogmi di fede’

Nei pazienti con fibrillazione atriale, il rischio di ictus cerebrale è davvero

più alto nelle donne che negli uomini?

1. Fang MC, Singer DE, Chang Y, Hylek EM, Henault LE , Jensvold NG, et al. Gender differences in the risk of ischemic stroke and peri pheral 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 H J. Refining clinical risk stratification for predicting stroke and thromboemb olism 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 a trial 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, Asing er RW. Factors associated with ischemic stroke during aspirin therapy in atrial fi brillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Stroke 1999;30:1 223-9.

6. Lane DA, Lip GY. Female gender is a risk factor f or stroke and thromboembolism in atrial fibrillation patients. Thromb Haemost 2009;1 01:802-5.

The risk of stroke in AF patients is higher in women than in men

Hart RG et alStroke. 1999;30:1223-1229

1. Female sex was also associated with a higher risk of fatal/disablingstroke (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).

Lip GYH et al. Chest 2010;137:263-272

The Stroke Risk in Atrial FibrillationWorking Group. Neurology

2007;69:546–554

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.

Hughes et alThromb Haemost 2008; 99: 295–304

1. Five studies found female sex to be a significant predictor for stroke.

2. Five studies did not find female sex to be a significantpredictor for stroke.

3. In one study, male sex was a significant predictor for stroke

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

Humphries KH et al. Circulation. 2001;103:2365-2370

Not significant trend

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

0

1

2

3

4

5

6

7

Women Men

6.2

4.2

Total population (global stroke rate 5.2%/year [722 1 pts with stroke])

Women vs men: HR 1.47 (1.40-1.54)

Friberg et al. BMJ 2012; 344:e3522

Absoluterate

ofstroke(x 100

subjectsper year)

Assessment of female sex as a risk factor in atrial fibrillation in Sweden:

Nationwide Retrospective Cohort Study

Friberg et al. BMJ 2012; 344:e3522

Men

WomenAge ≥ 75 y

Assessment of female sex as a risk factor in atrial fibrillation in Sweden:

Nationwide Retrospective Cohort Study

Friberg et al. BMJ 2012; 344:e3522

Friberg et al. BMJ 2012; 344:e3522

In pazienti con FA, il rischio di ictus èmaggiore 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 CHADS 2score da 0 a 3

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

Rifiniamo il paradigma….

Se una donna ha FA, ma la sua etàè 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

Friberg et al. BMJ 2012; 344:e3522Donna:

1. età < 652. Non FR

Uomo:1. Età < 65 con 1 FR2. Età 65-74, non FR

Donna:Età < 65 + 1 FREtà > 65, non FR

Uomo:1. Età > 75 anni, non FR2. Età 65-74 + 1 FR

Stroke rate in patients

with CHADS 2score 0-1

in relation to theCHA2DS2VASc

score

Uomo:1. Età < 65

senza FR

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

Olesen JB et al. Chest. 2012 Jan;141(1):147-53.

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 y ears . 4. Among 6,438 patients with NVAF, 2,002 (31.1%) were aged < 65 years.

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.

Alternativeoption

Bestoption

Atrial Fibrillation

Valvular Atrial Fibrillation

< 65 y and lone AF (including women)

Oral anticoagulant therapy(either Vitamin k antagonists or NOA )

0 1 ≥ 2

No antithrombotic therapy Novel anticoagulants Vitamin K antagonists

Yes

Yes

No

Camm AJ, Lip GY et al. ESC Guidelines 2012. Eur Heart J. 2012 Nov;33(21):2719-47

No

Class IIa Level A

Class IIa Level A

Class I Level A

Assess risk of stroke(CHA2DS2VASc score )

Grazie per la vostra attenzione

Grazie per la vostra attenzione