ACS & AMI UpdateWIN Program - SCAI 2010

Kimberly A. Skelding MD FSCAI FACC FAHAAssociate Interventional Cardiology

Geisinger Health SystemDanville, Pennsylvania

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ACS & AMI UpdateWIN Program - SCAI 2010

Kimberly A. Skelding. MD, FSCAI, FAHA, FACC

Nothing to Disclose

Gender Differences in Treatment• Late referrals

- more advanced CAD

- more urgent/emergent procedures

- longer DTB times in STEMI cases • Lower rates of IMA grafts in women even after adjustment for

age, extent of disease and urgent surgery• Similar benefits from GP IIb/IIIa agents and stents• Improved PCI mortality over time in both men and women

ClinCardiol 2007;30:491-5ClinCardiol 2007;30:491-5

Percutaneous Coronary InterventionPercutaneous Coronary Intervention

• Only 33% of PCI are performed in womenOnly 33% of PCI are performed in women annuallyannually• Delayed treatment with PCI in women is commonDelayed treatment with PCI in women is common

– Often >24 hours after presentationOften >24 hours after presentation• Women continue to be underrepresented in clinical Women continue to be underrepresented in clinical

trials of percutaneous coronary interventiontrials of percutaneous coronary intervention– They don’t meet They don’t meet inclusioninclusion criteria!!! criteria!!!

• Get there lateGet there late• More risk factors: older, worse renal functionMore risk factors: older, worse renal function• Sicker on presentationSicker on presentation

Blomkalns AL et al. J Am Coll Cardiol 2005;45:832-37, Lee et al. JAMA. Blomkalns AL et al. J Am Coll Cardiol 2005;45:832-37, Lee et al. JAMA. 2001;286:708-713, Harris DJ et al. N Engl J Med 2000;343(7):475-480, Simon V. Science 2005;308(5728):1517.2001;286:708-713, Harris DJ et al. N Engl J Med 2000;343(7):475-480, Simon V. Science 2005;308(5728):1517.

Outcomes following PCIOutcomes following PCI• Early data (1978-81) reported gender Early data (1978-81) reported gender

was independently predictive of was independently predictive of mortalitymortality

• Later data (1985-6), corrected for risk Later data (1985-6), corrected for risk factors, decreased but did not remove factors, decreased but did not remove the gender gapthe gender gap

• More recent data suggests no More recent data suggests no difference in death, MI, and emergent difference in death, MI, and emergent CABG but continued increased risk of CABG but continued increased risk of morbidity, particularly bleedingmorbidity, particularly bleeding

Cowley MJ et al. Circulation 1985;71(1):90-7, Kelsey SF. Circulation 1993;87(3):720-7, Argulian E et al. Am J Cowley MJ et al. Circulation 1985;71(1):90-7, Kelsey SF. Circulation 1993;87(3):720-7, Argulian E et al. Am J Cardiol 2006;96:48-53, Abbott JD et al. Am J Cardiol 2007;99:626-631, Thompson CA et al Catheter Cardiovasc Cardiol 2006;96:48-53, Abbott JD et al. Am J Cardiol 2007;99:626-631, Thompson CA et al Catheter Cardiovasc Interv 2006;67(1):25-31, Blomkalns AL et al. J Am Coll Cardiol 2005;45:832-37, Lansky AJ et al. Circulation Interv 2006;67(1):25-31, Blomkalns AL et al. J Am Coll Cardiol 2005;45:832-37, Lansky AJ et al. Circulation 2005;111:940-9532005;111:940-953

Outcomes following PCIOutcomes following PCI• Contemporary subacute or late thrombosis rates Contemporary subacute or late thrombosis rates

are similar between genders, 1.3% vs 1.2%, p=NSare similar between genders, 1.3% vs 1.2%, p=NS• Women are 61% more likely to present with in-Women are 61% more likely to present with in-

stent restenosis following drug eluting stents, stent restenosis following drug eluting stents, particularly diffuse in-stent restenosisparticularly diffuse in-stent restenosis– Harder to treatHarder to treat– Worse prognosisWorse prognosis

• 1.9x more women will return to the ER within 30 1.9x more women will return to the ER within 30 days of their intervention days of their intervention even after even after successful interventionssuccessful interventions

Abbott JD et al. Am J Cardiol 2007;99:626-631, Trabattoni D et al. Ital Heart J 2005;6:138-142, Hubbard BL et al. Abbott JD et al. Am J Cardiol 2007;99:626-631, Trabattoni D et al. Ital Heart J 2005;6:138-142, Hubbard BL et al.

Am J Cardiol 2007;99:197-201.Am J Cardiol 2007;99:197-201.

Differences Between Men and Women Undergoing PTCA

Clinical Observations Anatomy Explanation↑ unstable angina Less MV disease Spasm

Lower hemoglobin

↑ angina at f/u Similar rates of incomplete revasc.

Higher heart rateHigher BP

Fewer repeat PTCAs Similar restenosis rates Gender bias

↑ CHF Better EF Diastolic dysfunction

Women Have Higher Rate of Vascular Complications After PCI

Circ 2005;III;940-953Circ 2005;III;940-953

Vascular Complications are Decreasing

JInvCardiol 2007;369:372JInvCardiol 2007;369:372

Radial Approach is still Associated with More Bleeding in Women

• 1348 ACS patients pretreated with ASA, clopidogrel → radial PCI using 70 u/kg uFH and abciximab

(EASY trial of early discharge)

Women Men p valueSheath size – 5F

– 6F

57%

43%

44%

55%

0.0003

Hb drop 1.7% 0.4% 0.059

Hematoma 22% 5.8% 0.001

Final ACT (sec) 322 308 0.003

AHJ 2009; 157:740AHJ 2009; 157:740

Gender Differences in Response to Anticoagulants

• Among drug applications submitted to FDA between 1994 and 2000, 20% had gender differences in pharmacokinetics - gender differences in gastric emptying - more hepatic cytochrome CYP3A in women - more dietary supplements taken by women - more accumulation in fat - less renal excretion• Nine fold increase in HIT in women compared to men (Blood 2006;108:2937-410)

Bivalirudin Reduces (but does not eliminate) PCI Related Bleeding Differences

Between Men and Women

11.80%

4.90%

6.30%

2.50%

0.00%

2.00%

4.00%

6.00%

8.00%

10.00%

12.00%

14.00%

Women Men

(No

n-C

AB

G)

Maj

or

Ble

edin

g %

UFH+GPIIb/IIIaBivalirudin

(n=1401)(n=1401) (n=3779)(n=3779)

(p<0.001)(p<0.001)

(p<0.0001)(p<0.0001)

Lancet 2007;369:;907Lancet 2007;369:;907

AJC 2009;103:1197AJC 2009;103:1197

Are we still discriminating against

women, or are we using good clinical

judgment?

Dilemma• Women have atypical symptoms → physicians need high

level of suspicion and aggressive diagnostic testing, however . . . . .

• Women have higher rates of normal coronaries at the time of cath

• How can one avoid overutilization of cath, but at the same time avoid misdiagnosis in women?

– Noninvasive testing

– Determine pre-test probability of CAD

– CT angiography (avoid radiation exposure in younger women)

Gender differences in CAD significance after diagnostic cath for ACS

0

10

20

30

40

50

60

70

80

90

Black Hispanic N. Amer. Asian Caucasian

AC

S %

wit

h S

ign

ific

an

t C

AD

Women

Men

P<0.0001P<0.0001

N = 23,382 8,708 1,596 3,725 412,918

% Female

50.2 39.1 37.6 39.4 38

Circ 2008;117:1792Circ 2008;117:1792ACC/NCDR databaseACC/NCDR database

Differences in ACS Management• CURE trial data: 4,836 women and 7,726 men

with ACS– Women older, more diabetes, more

hypertension and hyperlipidemia. – Men more smoking, MI history, PAD and CVA.

• Women had fewer invasive procedures with ACS, 47.6% vs 60.5%, p=0.0001, regardless of risk

• No difference in CV death, MI or CVA if they presented with ACS.

• Women more likely to develop refractory angina and be re-hospitalized, (16.6% vs 13.9%, p=0.0001) after their first episode of ACS

Anand SS et al J Am Coll Cardiol 2005

Treatment of Women with Treatment of Women with Acute Coronary SyndromeAcute Coronary Syndrome

• Less likely to have an ECG done within 10 minutes of Less likely to have an ECG done within 10 minutes of presentationpresentation

• Less likely to be cared for by a cardiologist during their Less likely to be cared for by a cardiologist during their inpatient admissioninpatient admission

• Less likely to acutely be given appropriate pharmacotherapy Less likely to acutely be given appropriate pharmacotherapy such as heparin, aspirin, statins, ACE-Isuch as heparin, aspirin, statins, ACE-ILESS OFTEN RECEIVE GUIDELINE RECOMMENDED LESS OFTEN RECEIVE GUIDELINE RECOMMENDED

THERAPY BUT WOULD SIGNIFICANTLY BENEFIT FROM THERAPY BUT WOULD SIGNIFICANTLY BENEFIT FROM AN EARLY AGGRESSIVE INVASIVE STRATEGYAN EARLY AGGRESSIVE INVASIVE STRATEGY

Blomkalns AL et al. J Am Coll Cardiol 2005;45:832-37, Lansky AJ et al. Circulation Blomkalns AL et al. J Am Coll Cardiol 2005;45:832-37, Lansky AJ et al. Circulation 2005;111:940-953, Braunwald E et al. J Am Coll Cardiol 2002;40:1366-13742005;111:940-953, Braunwald E et al. J Am Coll Cardiol 2002;40:1366-1374

Outcome Following Treatment of Outcome Following Treatment of Acute Coronary SyndromeAcute Coronary Syndrome

• Young women, Young women, <<55 years old, have 55 years old, have >>2 times the risk of 2 times the risk of having a dissection or artery occlusion during their procedurehaving a dissection or artery occlusion during their procedure

• All women have increased bleeding and vascular access site All women have increased bleeding and vascular access site complications, those complications, those <<55 years old have >5 times the risk 55 years old have >5 times the risk compared to mencompared to men

• Following PCI, women with ACS have a 37% higher risk of Following PCI, women with ACS have a 37% higher risk of death, MI or rehospitalization than men with ACSdeath, MI or rehospitalization than men with ACS

• Women Women <<65 years old are at 46% higher risk of death, MI or 65 years old are at 46% higher risk of death, MI or rehospitalizationrehospitalization

Glaser R et al. Am J Cardiol 2006;98:1446-1450, Abbott JD et al. Am J CardiolGlaser R et al. Am J Cardiol 2006;98:1446-1450, Abbott JD et al. Am J Cardiol2007;99:626-631, Chauhan MS et al. Am J Cardiol 2005;95:101-104, Argulian E et al2007;99:626-631, Chauhan MS et al. Am J Cardiol 2005;95:101-104, Argulian E et alAm J Cardiol 2006;98:48-53, Lansky AJ et al. Circulation 2005;111:940-953, Am J Cardiol 2006;98:48-53, Lansky AJ et al. Circulation 2005;111:940-953, Anand SS et al. J Am Coll Cardiol 2005;46:1845-51.Anand SS et al. J Am Coll Cardiol 2005;46:1845-51.

Meta-Analysis of Invasive vs Conservative Rx for ACS

• Eight trials (3075 women and 7075 men)

• Women older, more comorbidites, but more likely to have insignificant (<50%) CAD at cath (24 vs 8% p<0.001)

JAMA 2008;300:71

Conclusions of ACS Meta-Analysis

• Men - Both high and low risk benefit from invasive

strategy• Women - High risk ACS women benefit from

invasive approach

- Low risk women may be treated

conservatively (but invasive approach

not harmful)

JAMA 2008;300:71JAMA 2008;300:71

Gender Differences in Atherosclerosis

• Plaque erosion as the etiology of coronary thrombosis and AMI occurs at a higher frequency in women than in men

• In an autopsy study of 291 patients who died of AMI and had coronary thrombosis, the prevalence of plaque erosions was 37% in women and 18% in men

Arbustini. Heart. 1999;82:269-272.

AA

CC

BB

DD

Gender Differences in AMI Management Persist:Get with the Guidelines Database 2001-2006

Measure/Treatment

Early medical therapy

Aspirin within <24 h

β-Blockers within <24 h

Invasive procedures

Cardiac catheterization

PCI

CABG

Revascularization

Any reperfusion therapy*

Primary PCI

Fibrinolytic Therapy

Fibrinolytic therapy + PCI

Timeliness of reperfusion*

DTN time median (25th-75th) min

DTB time median (25th – 75th) min

Men (n=47 556)

93.3

87.2

56.2

52.3

9.2

60.2

73.0

61.1

6.2

5.8

39.0

95.0

Women (n=30 698)

91.0

84.7

45.6

36.1

5.4

40.9 56.3

47.3

5.1

3.9

47.0

103.0

P value

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

<0.0001

*STEMI subpopulation (28.2% women, 35.1% men, p<0.0001)Circ 2008;118:2803Circ 2008;118:2803

Mechanism of MI May be Different in Women

• Spontaneous coronary dissection: women > men• Takotsubo (high circulating levels of

catecholamines): women > men• Spasm (migranes, Raynauds): women > men• Non-STEMI: women > men (subendocardial

ischemia due to LVH, microvascular disease, endothelial dysfunction)

Treatment of Acute Myocardial InfarctionTreatment of Acute Myocardial Infarction

• Women have longer door-to-balloon timesWomen have longer door-to-balloon times• Women are less likely to undergo invasive Women are less likely to undergo invasive

evaluation on the index admission regardless evaluation on the index admission regardless of ageof age

• Contemporary in-hospital and late mortality Contemporary in-hospital and late mortality rates are similar across genders when rates are similar across genders when treated in randomized controlled trials ~ treated in randomized controlled trials ~ treated irrespective of gendertreated irrespective of gender

Zahn R et al. Heart 2005;91(8):1041-6, Lansky AJ et al. Circulation 2005;111:940-953, Antman EM et al. Zahn R et al. Heart 2005;91(8):1041-6, Lansky AJ et al. Circulation 2005;111:940-953, Antman EM et al. Circulation. 2008 Jan 15;117(2):296-329, Reynolds HR et al. Arch Intern Med 2007;Circulation. 2008 Jan 15;117(2):296-329, Reynolds HR et al. Arch Intern Med 2007;167:2054-2060, Milcent C et al. Circulation 2007;115:833-839.167:2054-2060, Milcent C et al. Circulation 2007;115:833-839.

AMI in Women: AMI in Women: Later Presentation and Delay in TreatmentLater Presentation and Delay in Treatment

- CADILLAC Primary PCI Trial-- CADILLAC Primary PCI Trial-

Men WomenP

ValueN

Chest pain to ER (hrs)

ER to procedure (hrs)

Stent use

Abciximab use

1520

2.6 ± 2.5

1.9 ± 2.2

57%

54%

562

3.0 ± 2.6

2.1 ± 2.3

57%

51%

-

< 0.001

< 0.001

NS

NS

Outcomes Following 1st Myocardial Outcomes Following 1st Myocardial InfarctionInfarction

• 38% of women will die within one year versus 25% 38% of women will die within one year versus 25% of menof men

• Within 6 years 35% of women will have another MI Within 6 years 35% of women will have another MI vs 18% of menvs 18% of men

• More than twice as many women will be disabled More than twice as many women will be disabled with heart failure within 6 years of their first MIwith heart failure within 6 years of their first MI

• Women are 55% less likely to participate in cardiac Women are 55% less likely to participate in cardiac rehabilitationrehabilitation

• Women experience more depressive symptoms Women experience more depressive symptoms following AMI, particularly those following AMI, particularly those <<60 years old60 years old

Rosamond W et al. Circulation 2008;117:e25-146. Witt BJ et al. J Am Coll Cardiol 2004;44:988-Rosamond W et al. Circulation 2008;117:e25-146. Witt BJ et al. J Am Coll Cardiol 2004;44:988-996, Mallik S et al Arch Inern Med 2006;166:876-883.996, Mallik S et al Arch Inern Med 2006;166:876-883.

Primary PCI is Superior to Lytics in WomenMeta-Analysis - 23 Randomized Trials (PCAT-2)

9.6

14.4

5.3

7.17.7

8.5

3.54.9

0

2

4

6

8

10

12

14

16

≤ 2 hrs > 2 hrs ≤ 2 hrs > 2 hrs

30-D

ay M

ort

ali

ty

Lytic

Primary PCI

WomenWomen MenMen

What if we Treat Irrespective of Gender?

CAD in Women: Conclusions

• The risk factor profile in women presenting with ACS and AMI is distinctive compared to men. Women are older, have more HTN, DM, but less extensive CAD and better preserved LVEF.

• Despite having less extensive CAD, prognosis is worse than in men

• Symptoms may be atypical – even in the midst of AMI! Have a high level of suspicion

• In ACS and AMI women benefit from early invasive strategy and enoxaparin therapy.

Treat With Parity

• Use clinical judgement

• Be an advocate for women in your institution

• Look at your own local data

• Improve outcomes, improve your practice, improve enrollment in clinical trials