Stroke prevention in women imana dr shaneela malik

Stroke Prevention in Women IMANA 12th International Conference , Tanzania, Africa Shaneela Malik, MD Henry Ford Health System, Detroit MI

Disclosure  “IMANA is committed to providing CME activities that are fair, balanced and free of bias. Full and specific disclosure information is provided in your handouts.”  I have no relevant financial relationship with any commercial interest.

Overview

Outline     

Introduction Epidemiology Risk Factors Prevention Measures Conclusions

Introduction  Each year approximately 795,000 people experience a new or recurrent stroke  87% are ischemic; 10% ICH  Women have higher lifetime risk of stroke than men – It has been shown that the lifetime risk of stroke among those 55-75 was 1 in 5 (20-21%) for women and 1 in 6 (14-17%) for men

1. Heart Disease and Stroke Statistics – 2014 Update.

Circulation. 2014;129:e28-e292;

Introduction: Why is Prevention of Stroke in Women A Concern?  Third leading cause of death in women  About half of stroke survivors have residual deficits 6 months post-stroke – About 200,000 more disabled women with stroke than men

 Women are likely to be living alone and widowed before the stroke  More are institutionalized after the stroke  Women have poorer recovery from stroke than men

Epidemiology of Ischemic Stroke in Women  In the US, about 53.5% of the estimated 795,000 strokes occur in women  55,000 more women have strokes each year than men  Higher stroke mortality for women likely due to longer life expectancy  Of the approximate 130,000 deaths in 2009 (59.6%) were women

Epidemiology of Hemorrhagic stroke in Women  Several studies have shown that women have a higher incidence of subarachnoid hemorrhage than men  Nationwide Inpatient Sample reported that there were 2 x as many women discharged with ruptured/unruptured aneurysms than men  More prevalence of PCOMM aneurysms which has higher hemorrhage risk  No convincing evidence of increased risk of SAH in pregnancy or post-partum period 2

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2. Lin N et al. J Neurointerv Surgery 2012;3:78 3. Kim YM et al. Neurosurgery2013;72:143-149

Stroke Risk Factors Sex – Specific and More Common in Women

4. Bushnell et al. Guidelines for Prevention of Stroke in Women. Stroke May 2014

Sex Differences in Stroke Risk with Hypertension  Most Common Modifiable risk factor  Higher population-attributed risk  Differences between men and women occur – Prevalence – Treatment – Pathophysiology of hypertension

Hypertension Prevalence  Several studies have shown that women are more likely than men to have hypertension  INTERSTROKE study showed higher risk of stroke in women with self-reported BP  Women’s Health Initiative

5. Hsia J et al. Prehypertension and Cardiovascular Disease Risk in the Women’s Health Initiative. Circulation. 2007; 115:855-860

Hypertension Treatment  There is no specific trial looking at the effect of BP treatment in men vs women and stroke  However a meta-analysis of 31 clinical trials showed that treatment of hypertension in women aged >55 was associated with a 38% risk reduction in fatal and non-fatal strokes 6

6. Turnbull et al. Eur Heart Journal. 2008;29:2669-2680

Hypertension Treatment Does Race Make a Difference?  When looking at different races/ethnicities as well as ages there seems to be a benefit of BP reduction in younger and black women  A large systematic review showed : 7

– Treatment of BP in women 30-54 showed stroke risk reduction of 41% – Black women when looked at separately, treatment of BP showed stroke risk reduction of 53% 7. Quan A et al. Cochrane Database Systematic Review.

2000;(3):CD002146

Hypertension Sex, Treatment, And BP Goal  The prevalence of Hypertension in women increases with age (after age of 55 – so postmenopausal) – ? Role of sex hormone in blood pressure regulation

 Report ~ 75% of women >60 will develop hypertension

Hypertension and Treatment Does the Medication Matter?  No studies have looked at the response of medications between sexes – Diuretics were used more in women in the Framingham study – Diuretics and and ARBs were used in NHANES

 However getting BP controlled in women especially elderly (>80) is difficult

Does Medication Matter?

Side Effects  Women tend to be more sensative to side effects of certain meds – Diuretics – electrolyte imbalance – ACE-Inhibitor – cough – Calcium Channel Blocker – edema

 This can affect drug compliance rates in women thus affecting the ability to control the BP

Nonpharmacological Treatment of Blood Pressure for both Sexes  Modest reduction in salt intake for ≥ 4 weeks can lead to a significant decrease in blood pressure for hypertensive and normotensive people.  It’s recommended to reduce salt intake from 9-12g/day to 3 g/day to get good control of blood pressure 8. He FJ et al. Effect of longer-term modest salt reduction on blood pressure. Cochrane Database Syst Rev. 2012;(11):CD002003

Hypertension in Women of Childbearing Age  Prepregnancy hypertension increases risk of pre-eclampsia and eclampsia as well as stroke during pregnancy.  Choosing the right antihypertensive medication prior to pregnancy is important due to risk if continued during pregnancy

 Beta blockers – decreased risk of severe hypertension however can have fetal growth restriction  CCB – safe in pregnancy – mostly use nifedipine  Diuretics – safe. do not discontinue if pregnant  ACE-I, ARBs – contraindicated.

4. Bushnell et al. Guidelines for Prevention of Stroke in Women. Stroke May 2014

Pregnancy and Stroke  Stroke is uncommon in pregnancy (34 strokes per 100000 deliveries)  However in young women, stroke is higher in those pregnant than not  Highest risk in 3rd trimester and post-partum

Why does Pregnancy cause higher risk of Stroke?  Physiological changes of pregnancy – Venous stasis – Edema – Hypercoagulability  activated protein C resistance  Lower protein S  Increased fibrinogen

 Pregnancy-related hypertension main cause of ischemic and hemorrhagic stroke

Hypertension and Pregnancy  2 main causes of hypertension in pregnancy – Pre-eclampsia/eclampsia  Worsening high BP during pregnancy in the setting of proteinuria  Above with seizure = eclampsia

– Pregnancy-induced hypertension or gestational hypertension  No other signs or symptoms like in pre-eclampsia  Resolved 12 weeks post-partum

Risk Factors for Pregnancy-Induced Hypertension         

Obesity Age >40 Most Important Chronic hypertension predisposing factor Personal/family hx of pre-eclampsia Multiple pregnancy Pre-existing vascular disease Collagen vascular disease Diabetes Mellitus Renal disease

Just Cause You Delivered Doesn’t MEAN You’re off the Hook  Women who developed hypertension during pregnancy continue to have risk of stroke post-partum period.  In fact, postpartum pre-eclampsia is potentially more dangerous cause people are unaware of it.

Postpartum Pre-eclampsia  Associated with high risk of stroke  Can cause severe post-partum headaches  Transient elevations of BP is common – Volume redistribution – Alterations in vascular tone – Use of NSAIDS

 Persistent elevated BP should be treated

How Do We Reduce Hypertension in Pregnancy?  A 2010 Cochrane reviewed showed that hypertension in pregnancy can be reduced – Calcium supplementation ≥1 g/day

 A low dose aspirin can lower risk of preeclampsia as well  Recent research suggest that low vitamin D3 may be associated with increased preeclampsia (no definitive evidence)

Hypertension induced pregnancy Treatment  Association between blood pressure and stroke risk in pre-eclampsia is not linear therefore moderately high BP can be dangerous  Definitions of hypertension in pregnancy – Mild (140-149 / 90-99) – Moderate (150-159 / 100-109) – Severe (≥160 / ≥ 110)

 Treatment goal – maintain BP (130-155 / 80-105)

Hypertension induced pregnancy Treatment  Need to be careful not to lower BP too much because decreasing BP also decreases neonatal birth weight  Severe hypertension during pregnancy should be treated – American College of OB/GYN recommend labetalol as first-line drug – Avoid atenolol, ACE-I, ARBs

Magnesium Sulfate  Used for seizure prophylaxis however has been shown to decrease risk of stroke in women with severe hypertension and eclampsia  50% reduction of eclampsia with magnesium  Magnesium can lower BP a small amount but should not be monotherapy

Pregnancy complication and longterm risk of stroke  Women with history of pre-eclampsia – Increase risk of developing renal disease – 2-10 fold increase of chronic hypertension

 Gestational Diabetes – 50% of women go on to develop Type II DM within 5-10 years of pregnancy

Preeclampsia Prevention: Recommendations  Women with chronic or primary hypertension or previous pregnancy related hypertension – Low dose aspirin from 12th week gestation until delivery

 Calcium supplementation (≥1 g/day) considered to prevent preeclampsia

Pregnancy related Hypertension Recommendations  Severe hypertension (≥160 / ≥ 110) treat with safe antihypertensives such as labetolol or nifedipine  Consider treatment of moderate (150-159 / 100109) hypertension (decreases risk of severe htn)  Avoid atenolol, ACE-I and ARBs  After birth, continue meds and monitor BP closely because of risk of postpartum preeclampsia

Prevention of Stroke in Women with history of preeclampsia  Increase risk of stroke and hypertension 130 years after delivery – Start screening 6 months to 1 year post-partum – Document history of preeclampsia/eclampsia as a risk factor – Evaluate and treat other risk factors for cardiovascular disease  Obesity, smoking and dyslipidemia

Cerebral Venous Thrombosis  Manifests primarily as headache  0.5%-1% of ALL strokes  Overall incidence 1.32 per 100000 personyears  Higher in women than men (1.86 vs 0.75 per 100000 respectively)  Sex difference most prominent in women between ages 31 to 50 (incidence 2.78 per 100000)

Cerebral Venous Thrombosis Risk Factors  Hormonal factors – Oral contraceptives – Pregnancy – occurring in 3rd trimester and puerperium

 Inherited conditions – Antithrombin III, Protein C and Protein S deficiency – Factor V Leiden gene mutation

Cerebral Venous Thrombosis Treatment  Treatment is anticoagulation with IV unfractionated heparin or low molecular weight heparin  No studies done with newer anticoagulants  No studies done for duration of anticoagulation to prevent further CVT

Cerebral Venous Thrombosis Recurrence  In the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) recurrence of CVT was 2.2% and other thrombotic events 4.3%  Recent multi-national retrospective study studied 706 patients and followed them for 40 months (median) – Recurrence 4.4% – Most occurred after anticoagulation was stopped – No difference between unprovoked CVT and in those patients with known cause – Female sex alone did not show an increase risk of recurrent venous thromboembolic (VTE) event – Several recurrent VTE occurred in women when the first CVT occurred during pregnancy or was secondary to OC or Hormone therapy

 Most recurrence occurred within the first year of CVT  Recurrence is usually a VTE and not CVT, therefore one should be suspicious of other events (DVT, PE) in patients with hx of CVT

Sex Differences and Outcome in CVT  Mortality rate about 2.8%  Predictors of Poor outcome – – – –

Age Malignancy CNS infection Intracranial hemorrhage

 ISCVT showed that male sex was associated with poorer outcome – Significantly more women had complete recover within 6 months (81% vs 71%) – Likely due to “sex-specific” risk factors (pregnancy, OC, HT)

Pregnancy and CVT  Incidence of CVT in pregnant and post-partum is 1 in 2500 deliveries – Greatest risk in third trimester and first 4 weeks postpartum (up to 73%) – C-section delivery appears to be associated with higher risk of CVT

 CVT is not a contraindication for future pregnancies however many are on preventive antithrombotic medications  Women with hx of CVT may benefit with LMWH during future pregnancies for preventive measures

What to Order in Patients with CVT Recommendations  In patients with suspected CVT – Routine CBC, Chem 7, PT/PTT – Tests for hypercoaguable state  Protein C, Protein S, Antithrombin III deficiency – To be done 2-4 weeks after completion of anticoagulation – Limited value in acute setting or while on warfarin

 Antiphospholipid antibodies, Prothrombin G20210A mutation, Factor V Leiden

Treatment of CVT Recommendations  Provoked CVT – Warfarin for 3-6 months with target INR 2-3

 Unprovoked CVT – Warfarin for 6-12 months with target INR 2-3

 Recurrent CVT, VTE after CVT or first CVT with thrombophilia – Indefinite warfarin with target INR 2-3

Treatment of CVT Recommendations  Women with CVT during pregnancy – LMWH throughout pregnancy and then LMWH or warfarin for ≥ 6 weeks post partum (for a total minimum duration of 6 months therapy) – Can use LMWH at full dose instead of unfractionated heparin in acute CVT during pregnancy

 Future pregnancy and prevention of CVT – No contraindication to future pregnancy – Can consider prophylaxis with LMWH

Oral Contraceptives  Increasing number of women are using some type of contraceptive – Oral contraceptive use between 2006 and 2008 in US was 10.7 million women aged 15-44 – Risk factor of Stroke of other forms of hormonal contraception such as transdermal patch, vaginal ring and IUD is unknown

 Risk of stroke is low but incidence increases significantly with age (3.4 per 100000 in ages 15-19 to 64.4 per 100000 is women aged 4549)

Oral Contraceptive Ischemic Stroke Risk  There are several meta-analyses looking at risk of ischemic stroke and Oral contraceptive – One reviewed 16 studies and found a 2.75 fold increased risk with any OC – Another looked at low-dose OC and showed similar results – A review of progestogen-only OC showed no increase risk of stroke 9

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9. Gillum LA et al. Ischemic strke risk with oral contraceptives: a meta-analysis. JAMA 2000:284:72-78.

10. Baillargeon JP et al. Arch Intern Med. 2004:164:741-747 11. Chaktoura Z et al. Stroke. 2009;40: 1059-1062

What about other forms of Contraceptives?  Newer cohort study done in Denmark looked at 1.6 million women – Risk of ischemic stroke was 21.4 per 100000 personyears – RR of ischemic stroke for 30-40µg ethinyl estradiol was 1.40 (95% CI 0.97-2.03) – RR for 20µG dose was 0.88 (95% CI 0.22-3.53) – Progestin only didn’t show risk of stroke – Vaginal ring – 2.49 fold increase risk (95% CI 1.41-4.41)

Hemorrhagic Stroke and Oral Contraceptives  World Health Organization reported a slightly higher risk of hemorrhagic stroke with OC use  Studies in China have shown that some genetic mutations involving transcription factor regulating endothelial cell function as well as p53 activity have increase risk of stroke (both ischemic and hemorrhagic) with OC 12

12. Wang C et al. Hum Genetic 2012; 131:1337-1344

Other Risk Factors for Stroke and Oral Contraceptive Use  Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) Study : Showed increase risk of Ischemic stroke in OC users vs nonuser in the following: 13

– obesity and hx of hyperlipidemia – Women heterozygous for Factor V Leiden and MTHFR mutation – Acquired disorders: β2 glycoprotein antibodies but not anticardiolipin antibodies 13. Kemmeren JM et al. Stroke. 2002;33:1202-1208

Screening or No Screening  Given the data that show increase risk of stroke with OC use thrombophila, should women be prescreened prior to use?  There is a 15 fold odds of VTE in women with Factor V Leiden mutation using OC  Selective screening based on prior personal and family history is more cost-effective that universal screening

Migraine with Aura and OC use  Stroke Prevention in Young Women Study

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– Looked at 386 women with stroke (15-49 yo) and 614 age matched controls – Found 1.5 fold increase odd of stroke in women with migraine w/aura – If they smoked and used OC that risk 7.0 fold higher odds of stroke – However migraine w/ aura and only OC use was no further increase 14. MacCelellan LR et al. Stroke. 2007;38:2438-2445

Hypertension and hormonal contraceptive use: Risk of Stroke  Studies have shown that OC use can increase systolic blood pressure slightly (ENIGMA study)  Review of the literature have shown that there is no difference in stroke however in hypertensive women on OC and normotensive women on OC. 15

15. Curtis KM et al. Contraception. 2013;87: 611-624

Oral Contraceptives Recommendations  Oral contraceptive use in women with additional risk factors (cigarette smoking, prior VTE) may be harmful  Routine screening for prothrombotic mutations before initiation of OC is not useful  Measurement of BP before initiation of hormonal contraceptive is recommended

Menopause and Post-menopause hormonal therapy  In the Framingham Heart Study women with natural menopause before age 42 had twice the risk of stroke than those >42  However other studies have not shown any association between onset of menopause and risk of stroke

Post Menopausal Hormone Therapy  In the 1990’s observational studies suggested a potential benefit in hormone therapy and stroke prevention  Several primary and secondary stroke prevention studies were done to determine this benefit; However, evidence emerged showing a detrimental effect instead

Does Timing of Hormone Therapy Matter?  WHI study report – Women <10 years from menopause has no increased risk of Coronary Heart Disease with and CEE (HR 0.76) – Women ≥20 years post menopause had increase risk (HR 1.28)

Migraine with Aura ď&#x201A;§ Prevalence of Migraine with aura is about 4.4% (4 times higher in women) ď&#x201A;§ Although stroke with migraine is rare, there is at least a 2 fold increase risk of ischemic stroke in patients with migraine w/ aura ď&#x201A;§ This risk increases if women smoke or use oral contraceptive pills

Migraine with Aura Hemorrhagic Stroke  In Women’s Health Study showed an association with increase risk of hemorrhagic stroke, especially <55 years old  In pregnant women there is a large association with hemorrhagic stroke – Associated with pre-eclampsia and eclampsia

Migraine with Aura Recommendations  Logic plays a role here – Due to the association between higher migraine frequency and stroke risk, treatment of migraine might be reasonable  Although there is no evidence that treatment will reduce the risk of first stroke

– There is an increase risk of stroke in women with migraine with aura and those who smoke  So encourage smoking cessation

Obesity, Metabolic Syndrome AND Lifestyle Factors ď&#x201A;§ By 2030 an estimated 86% of Americans will be overweight or obese

16. Ogden C et al. Prevalence of Obesity Among Adults: United States, 2011-2012. NCNS Data Brief.No131 October 2013

Obesity  There are different terms for the type of obesity – Android obesity – high risk obesity  Was more frequently found in men and body fat was concentrated in the abdominal area

– Gynoid obesity – low-risk-lower body fat  More frequently found in premenopausal women

– Abdominal obesity – waist circumference >88cm in women and >102cm in men  Far more prevalent in women  2008 ages>20: 61.8% of women vs 43.7% male

Association between Obesity and Stroke  Obesity is an independent risk factor for stroke  Linear relationship btwn risk of stroke and BMI  No evidence that obesity impacts risk of stroke more in women than men

Abdominal Fat and Stroke  Abdominal obesity has a strong correlation with – – – –

Insulin resistence Dyslipidemia Diabetes mellitus Cerebrovascular disease

 Measured by waist circumference, waist to hip ratio and waist to stature ratio  2% increase risk of stroke in 1-unit increase waist circumference  Questionable sex difference

Metabolic Syndrome  Cluster of risk factors – – – –

Insulin resistance Abdominal adiposity Dyslipidemia Hypertension

 Affects 1/3 of the US population  Association between metabolic syndrome and stroke  Accounts for a larger percentage of stroke events in women than men (30% vs 4%)

Lifestyle  Reduce risk of CVD and mortality – – – – –

Healthy Diet Physical Activity Abstinence from smoking Moderate alcohol intake Maintenance of healthy BMI

 Recent primary prevention trial that assigned patients to Mediterranean diet with extravirgin olive oil or Mediterranean diet with nuts had lower odds of stroke or MI than usual diet.

Recommendations – Again Logic  Healthy lifestyle recommended for primary prevention – – – –

Regular exercise Moderate alcohol consumption (<1 drink/day) Abstinence from cigarette smoking Diet rich in fruits, vegetables, grains, nuts, olive oil, low in saturate fats (DASH diet)

 Lifestyle interventions focusing on diet and exercise are recommended for primary stroke prevention in individuals at high risk for stroke

Atrial Fibrillation  Most common arrhythmia and major modifiable risk factor  Risk of stroke is increased by 4 to 5 fold with a-fib – This risk increases with age from 1.5% for those aged 50-59 to nearly 25% for those aged >80

 About 60% of a-fib patients aged >75 are women

Atrial Fibrillation in Women  Get with The Guidelines-Stroke – One third hospital admission for stroke were patients >80 – A-fib found in 15.6% men and 20.4% women

 Women with a-fib have been shown to be slightly less likely to be treated with anticoagulation

Risk Stratification for Atrial Fibrillation  CHADS2 score – Congestive Heart Failure (1 point) – Hypertension (1 point) – Age ≥ 75 year (1 point) – Diabetes (1 point) – Prior Stroke/TIA (2 points)

 Score 0 – low risk (0.5%-1.7%)  Score 1 – moderate risk (1.2%-2.2%)  Score ≥ 2 – high risk (1.9% to 7.6%)

Risk Stratification for Women with Atrial Fibrillation  CHA2DS2-VASc Score – Congestive Heart Failure (1) – Hypertension (1) – Age  65-74 (1)  ≥ 75 (2)

– Diabetes (1) – Stroke/TIA (2) – Sex  Female (1)  Male (0)

– Hx of Vascular disease (1)  MI, PVD, Aortic plaque

      

Score 1 – risk 1.3% Score 2 – risk 2.2% Score 3 – risk 3.2% Score 4 – risk 4% Score 5 – risk 6.7% Score 6 – risk 9.8% Score 7 – risk 9.6% (had fewer patients)  Score 8 – risk 6.8% (had fewer patients)  Score 9 – risk 15.2%

Atrial Fibrillation and Women  Several cohort studies have showed an age-sex interaction in patients with A-Fib – Higher risk of stroke in women ≥75 with a-fib compared with men  Swedish study (100802 patients) showed risk of stroke greater in women than men (6.2% vs 4.2%)  Canadian study showed that women with a-fib ≥ 75 year old risk of stroke was 2.38% vs 1.95% in men that age 18

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18. Friberg L et al. BMJ. 2012:344:e3522

When to Anti-coagulate  European Society of Cardiology recommend anticoagulation with a CHA2DS2-VASc Score of ≥ 1 – However using that guideline then all women with a-fib would be anti-coagulated  Study in Sweden showed that patients aged ≤ 65 with other risk factors had a low risk of stroke regardless of sex (0.7% females, 0.5% male)  Study in Denmark showed that being female was the weakest of the risk factors having a non-significant increase in risk of thromboembolic events

What About the Newer Anticoagulants?  RELY – 18113 patients (36.4% female) – Fixed doses dabigatran (110mg or 150mg bid) vs warfarin – Outcome – stroke or systemic embolism

 ARISTOTLE – 18201 patients with Atrial fibrillation (35.3% female) – Apixaban 5mg bid vs warfarin – Outcome – ischemic or hemorrhagic stroke or systemic embolism

 ROCKET AF – 14264 patient s with nonvalvular AF (39.7% female) – Rivaroxaban (20mg) or dose adjusted warfarin – Outcome – stroke or systemic embolism

Should women have different dosage of medication than men  Women with AF had 30% higher concentration of dabigatran than males with same dose  Likely due to 30% lower creatinine clearance in women  Question remains should dosages change due to sex of patient?

Atrial Fibrillation Recommendations  Should use risk stratification tools in AF that account for sex and age differences  Given increased prevalence of AF with age and higher risk of stroke in elderly women with AF, active screening (women >75) is appropriate/recommended  Antiplatelet therapy for selected low-risk women (CHADS2=0 or CHA2DS2-VASc=1)

Atrial Fibrillation Recommendations  Consider newer anticoagulants in women with a-fib and do not have – Prosthetic heart valve – Hemodynamically significant valve disease – Severe renal failure (creatinine clearance 15 ml/min) – Lower weight (<50kg) – Advanced liver disease (impaired baseline clotting function)

Depression and Psychosocial Stress  Depression is associated with increased risk of stroke among both women and men  INTERSTROKE (Case-control study from 22 countries) – Self reported depression was associated with a 35% increased odds of stroke (adjusted for age, sex and region)  Defined as feeling sad, blue or depressed for ≥ 2 consecutive weeks during the past 12 months)

Depression and Psychosocial Stress  In the Nurses’ Health Study – Women with hx of depression had a 29% increased risk of stroke

 Another meta-analysis of studies of depression and stroke showed a pooled HR of 1.45 for stroke – There is no sex-specific analysis to determine if risk is greater in women than men

 Depression and stress in general is common in women.

Strategies for Prevention of Stroke: Are They Different in Women?  Lack of Represenation in Clinical Trials – Women have been underrepresented in NIH-funded stroke prevention trials – Analysis of women is flawed due to lack of power (type II error) – Enrollment of women in these studies is approximately 25%

 This lack of enrollment may be due to sex difference is disease prevalence as well as age of onset

CEA vs Medical Management for Symptomatic or Asymptomatic Carotid Stenosis

 Anatomy of internal carotid arteries is different in women than men – Smaller and shorter stenotic segments

 CEAs are done less often in women – Cohort study for Kaiser showed that although 47% of 20 the people with carotid stenosis were women    

Only 36.4% of them had CEA Time surgery was longer in women (35 days vs 18) Surgical group – women were older Outcome was similar in men and women in both CEA and medical management group

20. Poisson SN et al. Gender Differences in treatment of severe carotid stenosis after TIA. Stroke. 2010;41:1891-1895

CEA verses Carotid Artery Stenting  CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) – 35% (872 patients) were women – Rates of MI or death or ipsilateral stroke within 4 years for CAS vs CEA were 8.9% vs 6.7% in women and 6.2% vs 6.8% in men.

 Older patients did better with CEA and younger with CAS however there was no sex difference

Aspirin for Prevention of Stroke  Women’s Health Study looked at approximately 40,000 women (asymptomatic at first) age >45 – Took 100mg aspirin every other day vs placebo – 9% reduction in CVD (when stroke was looked at alone, reduction was 17%) – Rate of stroke was 0.11% per year in aspirin group vs 0.13% in placebo group

Aspirin  Adverse events  GI hemorrhage was more in aspirin group

 Benefit – Most consistent benefit for aspirin was in women ≥65 (cardiovascular event reduction of 26%, stroke reduction 30%)

Prevention of Stroke In Women Recommendations  Women with asymptomatic carotid stenosis should be screened for other treatable risk factors for stroke  In women who have CEA, aspirin is recommended unless contraindicated  Prophylactic CEA performed with <3% morbidity/mortality can be useful in highly selected patients with an asymptomatic carotid stensois (60% by angiogram and 70% doppler)

Recommenations  Women with recent TIA or ischemic stroke within past 6 months and ipsilateral severe (70-99%) carotid stenosis – CEA is recommended if the peri-operative morbidity and mortality risk is estimated to be <6%  Women with recent TIA or stroke and ipsilateral moderate (50-69%) stenosis – CEA is recommended depending on patient-specific factors, such as age and co-morbidities, if peri-operative morbidity and mortality risk is estimated to be 6%  Should do CEA within 2 weeks if possible

Recommendations  Aspirin therapy (75-325mg) is reasonable in women with diabetes mellitus unless contraindicated  If high risk (10 yr CVD risk ≥10%) women have an indication for aspirin. If cannot tolerate use clopidogrel  Aspirin therapy can be useful in women ≥65 if BP is controlled and benefit for ischemic stroke and MI prevention likely to outweigh risk of GI Bleed and hemorrhagic stroke

Conclusions  There are factors that are specific to women – OCP use – Pregnancy – Post menopausal hormone therapy  Other factors are more common in women – Hypertension – Depression – Atrial fibrillation

 Prevention data is limited due to low enrollment of women in clinical trials

What’s Needed in the Future  Epidemological studies in women for subtypes of stroke such as hemorrhages  Improve stroke awareness, especially in childbearing age women due to increase risk of stroke in this population  Improve awareness of risk factors in younger women due to the fact that obesity, dm, htn occur more frequently in young

Disclosure  “IMANA is committed to providing CME activities that are fair, balanced and free of bias. Full and specific disclosure information is provided in your handouts.”  I have no relevant financial relationship with any commercial interest.

Thank you!