Gender Differences in the Risk of Ischemic Stroke and Peripheral Embolism in Atrial Fibrillation: The AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) Study Increased risk of first-ever stroke in younger patients with atrial fibrillation not recommended for antithrombotic therapy by current guidelines: a population-based study in an East Asian cohort of 22 million people. Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: NICE guidance Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Gender differences in stroke risk of atrial fibrillation patients on oral anticoagulant treatment. 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. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study.
Background —Previous studies provide conflicting results about whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation ( AF ) . We examined data from a large contemporary cohort of AF patients to address this question . Methods and Results —We prospect ively studied 13 559 adults with AF and recorded data on patients ’ clinical characteristics and the occurrence of incident hospitalizations for ischemic stroke , peripheral embolism , and major hemorrhagic events through search ing vali date d computerized data bases and medical record review . We compared event rates by patient sex using multivariable log-linear regression , adjusting for clinical risk factors for stroke , and stratifying by warfarin use . We identified 394  ischemic stroke and peripheral embolic events during 15 494 person-years of follow-up off warfarin . After multivariable analysis , women had higher annual rates of thromboembolism off warfarin than did men ( 3.5 % versus 1.8 % ; adjusted rate ratio [ RR ] , 1.6 ; 95 % CI , 1.3 to 1.9 ) . There was no significant difference by sex in 30-day mortality after thromboembolism ( 23 % for both ) . Warfarin use was associated with significantly lower adjusted thromboembolism rates for both women and men ( RR , 0.4 ; 95 % CI , 0.3 to 0.5 ; and RR , 0.6 ; 95 % CI , 0.5 to 0.8 , respectively ) , with similar annual rates of major hemorrhage ( 1.0 % and 1.1 % , respectively ) . Conclusions —Women are at higher risk than men for AF-related thromboembolism off warfarin . Warfarin therapy appears be as effective in women , if not more so , than in men , with similar rates of major hemorrhage . Female sex is an independent risk factor for thromboembolism and should influence the decision to use anticoagulant therapy in persons with AF OBJECTIVE To assess the risk of first-ever ischemic stroke in younger patients with atrial fibrillation ( AF ) who have none of the CHA2DS2-VASc ( congestive heart failure , hypertension , age ≥75 years , diabetes mellitus , previous stroke/transient ischemic attack , vascular disease , age 65 - 74 years , sex category [ female sex ] ) risk factors ( excluding female sex ) by using the National Health Insurance research data base in Taiwan . PATIENTS AND METHODS From 22,842,778 insured people , we identified 24,612 hospitalized patients with newly diagnosed AF between January 1 , 2002 , and December 31 , 2004 , as the AF group and r and omly selected 98,448 age- and sex-matched persons without AF as the non-AF group . Both groups were followed up until December 31 , 2010 , to estimate ischemic stroke incidences in relation to other stroke risk factors . RESULTS During a follow-up period of 89,468 person-years , the stroke rate was higher in patients with AF than in those without AF ( 5.79 per 100 person-years vs 2.25 per 100 person-years ) . The higher prevalence of CHA2DS2-VASc comorbidities ( heart failure , hypertension , diabetes , coronary artery disease , and peripheral artery disease ) in patients with AF further increased the stroke risk . In 790 patients with AF aged 30 to 55 years who had none of the CHA2DS2-VASc comorbidities at baseline and retained a " low risk , " that is , those with a CHA2DS2-VASc score of 0 in men and 1 in women during follow-up , the stroke rate remained considerably higher than that in their non-AF counterparts ( 1.00 per 100 person-years vs 0.25 per 100 person-years ) , with a sex-adjusted hazard ratio of 4.09 ( 95 % CI , 2.97 - 5.62 ) . CONCLUSION This study finds an increased risk of stroke in younger patients with AF who are not recommended for prevention of thromboembolism by current guidelines . Better stroke risk stratification tools are needed to prioritize younger patients with AF for thromboprophylactic therapy in this population Atrial fibrillation ( AF ) is the commonest sustained cardiac arrhythmia , whose importance has been realised given its strong association with stroke and systemic embolism that can be significantly reduced by oral anticoagulation . Until recently , the only oral anticoagulant ( OAC ) available was the vitamin K antagonist ( VKA ) class of drugs — for example , warfarin . Indeed , warfarin provides highly effective prophylaxis against thromboembolism as shown by extensive evidence from r and omised controlled trials , but its effectiveness is dependent upon good anticoagulation control ( as reflected by its high length of time in the therapeutic range).1 The risk of stroke in AF is not homogeneous , and depends upon the presence or absence of several risk factors . These risk factors have been used to formulate stroke risk stratification schemes , so that the focus has been to identify ‘ high-risk ’ patients who could be targeted for this ‘ inconvenient ’ drug , warfarin . The numerous practical limitations which affect a clinician 's willingness to prescribe warfarin , and a patient 's willingness to comply with it ( box 1 ) , have result ed in large numbers of high-risk patients either unprotected against stroke or suboptimally protected with antiplatelet therapy2—despite evidence that aspirin is less effective for stroke prevention and is not without its own bleeding risk , especially in the elderly.3 Box 1 # # # Limitations of warfarin The limitations of warfarin have driven efforts to establish new OACs which can circumvent the shortcomings of the VKAs . The new OACs fall into two classes : the oral direct thrombin inhibitors ( eg , dabigatran ) and the oral factor Xa inhibitors ( eg . rivaroxaban , apixaban).4 The National Institute for Health The Canadian Cardiovascular Society ( CCS ) published the complete set of 2010 Atrial Fibrillation ( AF ) Guidelines in the January , 2011 issue of the Canadian Journal of Cardiology . During its deliberations , the CCS Guidelines Committee engaged to a timely review of future evidence , with periodic composition of focused up date s to address clinical ly important advances . In 2011 , results were published from 3 pivotal AF trials : the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonist for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ( ROCKET-AF ) , the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation ( ARISTOTLE ) study , and the Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of St and ard Therapy ( PALLAS ) , comparing dronedarone with placebo in patients with permanent AF and additional cardiovascular disease risk-factor burden . Each of these large r and omized trials provided clear results with major implication s for AF management . Other important evidence that has emerged since the 2010 Guidelines includes findings about prediction instruments for AF-associated stroke and bleeding risk , stroke risk in paroxysmal-AF patients , risk-benefit considerations related to oral anticoagulation in patients with chronic kidney disease , and risk/benefit considerations in the use of antiplatelet agents , alone and in combination with each other or with oral anticoagulants , in AF patients . The Guidelines Committee judged that this extensive and important new evidence required focused updating of the 2010 Guidelines with respect to stroke prevention and rate/rhythm control . This report presents the details of the new recommendations , along with the background and rationale The efficacy of adjusted-dose oral anticoagulant treatment ( OAT ) in the prevention of stroke in atrial fibrillation ( AF ) is well documented . Available data show that AF patients are widely heterogeneous in terms of ischaemic stroke risk . The role of female gender as a predictor of stroke risk is inconsistent , in particular it is unclear if warfarin treatment is able to prevent stroke equally in both sexes . We performed a prospect i ve study on 780 AF patients on OAT , followed by an Anticoagulation Clinic , to evaluate if female gender is a risk factor for stroke among patients on OAT  and if the quality of anticoagulation is different between genders . No difference was found in relation to the quality of anticoagulation between genders ( p=0.5 ) . During follow-up 33 patients had major bleedings ( rate 1.37 x 100 pt/yrs ) but no difference was found between genders in bleeding risk . Forty patients had ischaemic events [ rate 1.66 x 100 pt/yrs ; males rate 1.2 x 100 pt/yrs ; females rate 2.43 x 100 pt/yrs ; p=0.042 ; relative risk ( RR ) of females vs. males 2.0 ( 95 % confidence interval [ CI ] 1.3 - 3.1 ) ; p= 0.004 ] . The higher rate of ischaemic events in females with respect to males was confirmed at Cox regression analysis after correction for age ( p=0.009 ) . In addition , strokes occurring in females were more disabling , and RR for severe and fatal stroke , defined according to Modified Rankin scale , of females vs. males was 3.1 ( 95 % CI 1.3 - 6.5 ; p=0.001 ) . In conclusion , our data show a higher risk of stroke in anticoagulated AF females with respect to males , despite a similar quality of anticoagulation BACKGROUND AND PURPOSE Nonvalvular atrial fibrillation ( AF ) is a strong , independent risk factor for stroke , but the absolute rate of stroke varies widely among AF patients , importantly influencing the potential benefit of antithrombotic prophylaxis . We explore factors associated with ischemic stroke in AF patients taking aspirin .  METHODS We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low , inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years , during which 130 ischemic strokes were observed . RESULTS Age ( relative risk [RR]=1.8 per decade , P<0.001 ) , female sex ( RR=1.6 , P=0.01 ) , history of hypertension ( RR=2.0 , P<0.001 ) , systolic blood pressure > 160 mm Hg ( RR=2.3 , P<0.001 ) , and prior stroke or transient ischemic attack ( RR=2.9 , P<0.001 ) were independently associated with increased stroke risk . Regular consumption of > /=14 alcohol-containing drinks per week was associated with reduced stroke risk ( adjusted RR=0.4 , P=0.04 ) . Among SPAF III participants , estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke ( adjusted RR=3.2 , P=0.007 ) . With the use of these variables , a risk stratification scheme for primary prevention separated participants into those with high ( 7.1%/y , 22 % of the cohort ) , moderate ( 2.6%/y , 37 % of the cohort ) , and low ( 0.9%/y , 41 % of the cohort ) rates of stroke . Ischemic strokes in low-risk participants were less often disabling ( P<0.001 ) . CONCLUSIONS Patients with AF who have high and low rates of stroke during treatment with  aspirin can be identified . However , validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management . Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF , but these findings require confirmation AIMS The impact of some risk factors for stroke and bleeding , and the value of stroke and bleeding risk scores , in atrial fibrillation ( AF ) , has been debated , as clinical trial cohorts have not adequately tested these . Our objective was to investigate risk factors for stroke and bleeding in AF , and application of the new CHA(2)DS(2)-VASc and HAS-BLED schemes for stroke and bleeding risk assessment s , respectively . METHODS AND RESULTS We used the Swedish Atrial Fibrillation cohort study , a nationwide cohort study of 182 678 subjects with a diagnosis of AF at any Swedish hospital between 1 July 2005 and 31 December 2008 , who were prospect ively followed for an average of 1.5 years ( 260 000 years at risk ) . With the use of the National Swedish Drug Registry , all patients who used an oral anticoagulant  anytime during follow-up were identified . Most of the analyses were made on a subset of 90 490 patients who never used anticoagulants .  Risk factors for stroke , the composite thromboembolism endpoint ( stroke , TIA , or systemic embolism ) , and bleeding , and the performance of published stroke and bleeding risk stratification schemes were investigated . On multivariable analysis , significant associations were found between the following ' new ' risk factors and thromboembolic events ; peripheral artery disease [ hazard ratio ( HR ) 1.22 ( 95 % CI 1.12 - 1.32 ) ] , ' vascular disease ' [ HR 1.14 ( 1.06 - 1.23 ) ] , prior myocardial infa rct ion [ HR 1.09 ( 1.03 - 1.15 ) ] , and female gender [ HR 1.17 ( 1.11 - 1.22 ) ] . Previous embolic events , intracranial haemorrhage ( ICH ) , hypertension , diabetes , and renal failure were other independent predictors of the composite thromboembolism endpoint , while thyroid disease ( or hyperthyroidism ) was not an independent stroke risk factor . C-statistics for the composite thromboembolic endpoint with the CHADS(2 ) and CHA(2)DS(2)-VASc schemes were 0.66 ( 0.65 - 0.66 ) and 0.67 ( 0.67 - 0.68 ) , respectively . On multivariable analysis , age , prior ischaemic stroke or thromboembolism , prior major bleeding events , and hypertension were significant predictors of ICH and major bleeding . Heart failure , diabetes , renal failure , liver disease , anaemia or platelet/coagulation defect , alcohol abuse , and cancer were other significant predictors for major bleeding , but not ICH . The ability for predicting ICH and major bleeding with both bleeding risk schemes ( HEMORR(2)HAGES , HAS-BLED ) were similar , with c-statistics of ~0.6 . CONCLUSION Several independent risk factors ( prior ICH , myocardial infa rct ion , vascular disease , and renal failure ) predict ischaemic stroke and /or the composite thromboembolism endpoint in AF , but thyroid disease ( or hyperthyroidism ) was not an independent risk factor for stroke . There is a better performance for CHA(2)DS(2)-VASc over CHADS(2 ) schemes for the composite thromboembolism endpoint . While both tested bleeding risk schemes have similar predictive value , the HAS-BLED score has the advantage of simplicity
Women with AF are at increased risk of stroke , particularly elderly women .
BACKGROUND Atrial fibrillation ( AF ) increases the risk of stroke , but this risk is not homogenous .
Many risk factors contribute to stroke risk however , the evidence for female sex as a risk factor is less well-established .
AIM To perform a systematic review and meta- analysis of the available evidence to establish if female sex is a risk factor for stroke/thromboembolism among patients with AF .