Stroke Prevention in Women

IMANA 12th International Conference , Tanzania, Africa

Shaneela Malik, MDHenry 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 men2

More prevalence of PCOMM aneurysms which has higher hemorrhage risk

No convincing evidence of increased risk of SAH in pregnancy or post-partum period3

2. Lin N et al. J Neurointerv Surgery 2012;3:78

3. Kim YM et al. Neurosurgery2013;72:143-149

Stroke Risk Factors

Sex – Specificand 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

HypertensionPrevalence

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

HypertensionTreatment

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 strokes6

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

Hypertension TreatmentDoes 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 showed7:– 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

HypertensionSex, 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 TreatmentDoes 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 Chronic hypertension Personal/family hx of pre-eclampsia Multiple pregnancy Pre-existing vascular disease Collagen vascular disease Diabetes Mellitus Renal disease

Most Important predisposing factor

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 pre-eclampsia as well

Recent research suggest that low vitamin D3 may be associated with increased pre-eclampsia (no definitive evidence)

Hypertension induced pregnancyTreatment

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 pregnancyTreatment

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 long-term 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 HypertensionRecommendations

Severe hypertension (≥160 / ≥ 110) treat with safe antihypertensives such as labetolol or nifedipine

Consider treatment of moderate (150-159 / 100-109) 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 1-30 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 person-

years 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 ThrombosisRisk 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 ThrombosisTreatment

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 ThrombosisRecurrence

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 post-

partum (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 CVTRecommendations

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 CVTRecommendations

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 CVTRecommendations

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 45-49)

Oral ContraceptiveIschemic 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 OC9

– Another looked at low-dose OC and showed similar results10

– A review of progestogen-only OC showed no increase risk of stroke11

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 person-

years– 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 OC12

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) Study13: Showed increase risk of Ischemic stroke in OC users vs nonuser in the following: – 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 pre-screened 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 Study14

– 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 ContraceptivesRecommendations

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

Prevalence of Migraine with aura is about 4.4% (4 times higher in women)

Although stroke with migraine is rare, there is at least a 2 fold increase risk of ischemic stroke in patients with migraine w/ aura

This risk increases if women smoke or use oral contraceptive pills

Migraine with AuraHemorrhagic 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 AuraRecommendations

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

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 withAtrial 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%)18

Canadian study showed that women with a-fib ≥ 75 year old risk of stroke was 2.38% vs 1.95% in men that age19

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

19. Avgil T et al. JAMA. 2012:307:1952-1958

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 FibrillationRecommendations

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 FibrillationRecommendations

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

the people with carotid stenosis were women20

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 WomenRecommendations

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!