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: verdec@tin.it
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 CHA 2 DS 2 VASc = 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 Women vs men: HR 1.47 (1.40-1.54) Absolute rate of stroke (x 100 subjects per year) 6 5 4 3 2 6.2 4.2 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 CHADS 2 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 CHADS 2 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 CHA 2 DS 2 VASc, il rischio di ictus ischemico è basso e non sono necessari farmaci antitrombotici
Friberg et al. BMJ 2012; 344:e3522
Uomo: 1. Età < 65 con 1 FR 2. Età 65-74, non FR Uomo: 1. Età < 65 senza FR Uomo: 1. Età > 75 anni, non FR 2. Età 65-74 + 1 FR Donna: Età < 65 + 1 FR Età > 65, non FR Stroke rate in patients with CHADS 2 score 0-1 in relation to the CHA 2 DS 2 VASc score Donna: 1. età < 65 2. Non FR Friberg et al. BMJ 2012; 344:e3522
Stroke and Thromboembolism in Patients Aged < 65 Years: The CHA 2 DS 2 -VASc Risk Factors Excluding Age Risk Factor Univariate HR (95% CI) Interaction with VKA [a] HR (95% CI) Multivariate 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 (CHADS 2 score 0-3, without previous stroke or myocardial infarction). 3. In male and female AF patients aged < 65 y and without other RFs (CHA 2 DS 2 VASc = 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 Valvular Atrial Fibrillation Yes Yes No < 65 y and lone AF (including women) No Assess risk of stroke (CHA 2 DS 2 VASc score) 0 1 2 Class IIa Level A Class I Level A Oral anticoagulant therapy (either Vitamin k antagonists or NOA) Best option Class IIa Level A Alternative option No antithrombotic therapy Novel anticoagulants Vitamin K antagonists Camm AJ, Lip GY et al. ESC Guidelines 2012. Eur Heart J. 2012 Nov;33(21):2719-47
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