Atherosclerotic plaque morphology differs in women and men. Acute coronary thrombosis results from 2 different types of plaque morphologies: plaque rupture and plaque erosion. Arbustini et al evaluated the prevalence of plaque erosion as a substrate for coronary thrombosis through a pathological study in patients with acute MI not treated with thrombolysis or coronary interventional procedures. This figure shows plaque erosion in 4 sections; the thrombus outlines the profile of the plaque, and there is no evidence of continuity between thrombus and plaque core. 34 Acute coronary thrombi were found in 291 hearts (98%); in 74 cases (25%) 40/107 women (37.4%) and 34/184 men (18.5%; P =.0004) the plaque substrate for thrombosis was erosion. 34 Plaque erosion is an important substrate for coronary thrombosis in patients who die of acute MI, and its prevalence is significantly higher in women than in men. 34 34. Arbustini E, Dal Bello B, Morbini P, et al. Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction. Heart . 1999;82:269-272.
ACS & AMI UpdateWIN Program - SCAI 2010Kimberly A. Skelding MD FSCAI FACC FAHA Associate Interventional Cardiology Geisinger Health System Danville, Pennsylvania
Disclosure Information ACS & AMI Update WIN Program - SCAI 2010Kimberly 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;30:491-5
Percutaneous Coronary Intervention • Only 33% of PCI are performed in women annually • Delayed treatment with PCI in women is common – Often >24 hours after presentation • Women continue to be underrepresented in clinical trials of percutaneous coronary intervention – They don’t meet inclusion criteria!!! • Get there late • More risk factors: older, worse renal function • Sicker on presentationBlomkalns 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.
Outcomes following PCI• Early data (1978-81) reported gender was independently predictive of mortality• Later data (1985-6), corrected for risk factors, decreased but did not remove the gender gap• More recent data suggests no difference in death, MI, and emergent CABG but continued increased risk of morbidity, particularly bleedingCowley MJ et al. Circulation 1985;71(1):90-7, Kelsey SF. Circulation 1993;87(3):720-7, Argulian E et al. Am JCardiol 2006;96:48-53, Abbott JD et al. Am J Cardiol 2007;99:626-631, Thompson CA et al Catheter CardiovascInterv 2006;67(1):25-31, Blomkalns AL et al. J Am Coll Cardiol 2005;45:832-37, Lansky AJ et al. Circulation2005;111:940-953
Outcomes following PCI • Contemporary subacute or late thrombosis rates are similar between genders, 1.3% vs 1.2%, p=NS • Women are 61% more likely to present with in- stent restenosis following drug eluting stents, particularly diffuse in-stent restenosis – Harder to treat – Worse prognosis • 1.9x more women will return to the ER within 30 days of their intervention even after successful interventionsAbbott 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.
Differences Between Men and Women Undergoing PTCAClinicalObservations Anatomy Explanation↑ unstable angina Less MV disease Spasm Lower hemoglobin↑ angina at f/u Similar rates of Higher heart rate incomplete revasc. Higher BPFewer repeat PTCAs Similar restenosis rates Gender bias↑ CHF Better EF Diastolic dysfunction
Women Have Higher Rate ofVascular Complications After PCI Circ 2005;III;940-953
Vascular Complications are Decreasing JInvCardiol 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 value Sheath size – 5F 57% 44% 0.0003 – 6F 43% 55% Hb drop 1.7% 0.4% 0.059 Hematoma 22% 5.8% 0.001 Final ACT (sec) 322 308 0.003 AHJ 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 (p<0.001) UFH+GPIIb/IIIa Bivalirudin(Non-CABG) Major Bleeding % 14.00% 11.80% 12.00% 10.00% (p<0.0001) 8.00% 6.30% 6.00% 4.90% 4.00% 2.50% 2.00% 0.00% (n=1401) (n=3779) Lancet 2007;369:;907 Women Men AJC 2009;103:1197
Are we stilldiscriminating 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 P<0.0001 90 Women ACS % with Significant CAD 80 Men 70 60 50 40 30 20 10 0 Black Hispanic N. Amer. Asian Caucasian N= 23,382 8,708 1,596 3,725 412,918 % 50.2 39.1 37.6 39.4 38 Female Circ 2008;117:1792ACC/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 Acute Coronary Syndrome• Less likely to have an ECG done within 10 minutes of presentation• Less likely to be cared for by a cardiologist during their inpatient admission• Less likely to acutely be given appropriate pharmacotherapy such as heparin, aspirin, statins, ACE-I LESS OFTEN RECEIVE GUIDELINE RECOMMENDED THERAPY BUT WOULD SIGNIFICANTLY BENEFIT FROM AN EARLY AGGRESSIVE INVASIVE STRATEGY 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;40:1366-1374
Outcome Following Treatment of Acute Coronary Syndrome• Young women, <55 years old, have >2 times the risk of having a dissection or artery occlusion during their procedure• All women have increased bleeding and vascular access site complications, those <55 years old have >5 times the risk compared to men• Following PCI, women with ACS have a 37% higher risk of death, MI or rehospitalization than men with ACS• Women <65 years old are at 46% higher risk of death, MI or rehospitalization Glaser R et al. Am J Cardiol 2006;98:1446-1450, Abbott JD et al. Am J Cardiol 2007;99:626-631, Chauhan MS et al. Am J Cardiol 2005;95:101-104, Argulian E et al 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.
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;300:71
Gender Differences in Atherosclerosis• Plaque erosion as the etiology of coronary thrombosis and AMI A B 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, C the prevalence of plaque D erosions was 37% in women and 18% in menArbustini. Heart. 1999;82:269-272.
Gender Differences in AMI Management Persist: Get with the Guidelines Database 2001-2006 Measure/Treatment Men (n=47 556) Women (n=30 698) P value Early medical therapy Aspirin within <24 h 93.3 91.0 <0.0001 β-Blockers within <24 h 87.2 84.7 <0.0001 Invasive procedures Cardiac catheterization 56.2 45.6 <0.0001 PCI 52.3 36.1 <0.0001 CABG 9.2 5.4 <0.0001 Revascularization 60.2 40.9 <0.0001 Any reperfusion therapy* 73.0 56.3 <0.0001 Primary PCI 61.1 47.3 <0.0001 Fibrinolytic Therapy 6.2 5.1 Fibrinolytic therapy + PCI 5.8 3.9 Timeliness of reperfusion* DTN time median (25th-75th) min 39.0 47.0 <0.0001 DTB time median (25th – 75th) min 95.0 103.0 <0.0001 Circ 2008;118:2803*STEMI subpopulation (28.2% women, 35.1% men, p<0.0001)
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 Infarction • Women have longer door-to-balloon times • Women are less likely to undergo invasive evaluation on the index admission regardless of age • Contemporary in-hospital and late mortality rates are similar across genders when treated in randomized controlled trials ~ treated 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. 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.
AMI in Women: Later Presentation and Delay in Treatment - CADILLAC Primary PCI Trial- P Men Women ValueN 1520 562 -Chest pain to ER (hrs) 2.6 ± 2.5 3.0 ± 2.6 < 0.001ER to procedure (hrs) 1.9 ± 2.2 2.1 ± 2.3 < 0.001Stent use 57% 57% NSAbciximab use 54% 51% NS
Outcomes Following 1st Myocardial Infarction • 38% of women will die within one year versus 25% of men • Within 6 years 35% of women will have another MI vs 18% of men • More than twice as many women will be disabled with heart failure within 6 years of their first MI • Women are 55% less likely to participate in cardiac rehabilitation • Women experience more depressive symptoms following AMI, particularly those <60 years oldRosamond 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.
Primary PCI is Superior to Lytics in WomenMeta-Analysis - 23 Randomized Trials (PCAT-2) 16 Lytic 14.4 14 Primary PCI 30-Day Mortality 12 9.6 10 8.5 7.7 8 7.1 6 5.3 4.9 3.5 4 2 0 ≤ 2 hrs > 2 hrs ≤ 2 hrs > 2 hrs Women Men
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