DrugEluting Stents In AMI A Proven Strategy James

Drug-Eluting Stents In AMI: A Proven Strategy? James Hermiller, MD, FACC, FSCAI St Vincent Hospital Indianapolis, IN

DISCLOSURES James Hermiller, MD Consulting Fees – Abbott Vascular, Boston Scientific Corporation, St. Jude Medical I intend to reference unlabeled/ unapproved uses of drugs or devices in my presentation. I intend to reference date and guidelines for drug-eluting stents.

Outline • Introduction • Randomized clinical trials • Registry studies • The guidelines • Summary

Introduction • Role of DES in the setting of STEMI has been uncertain due to: • DES associated delayed healing with thrombus and the concern about subsequent incomplete stent apposition • Does this lead to higher probability of stent thrombosis, MI and death with DES vs BMS • TLR and restenosis rates tend to be lower in STEMI vs. elective PCI patients • Outcomes from RCTs and registry studies of DES vs. BMS in STEMI have been conflicting

Introduction Stent Thrombosis • Stent Malapposition • Compliance DAP Restenosis

Premature Discontinuation of Thienopyridine Therapy After DES Implantation Spertus JA et al. Circulation 2006; 113: 2803 -9 Multicenter, prospective PREMIER registry in patients admitted with myocardial infarction -500 DES patients enrolled at 19 sites • -68500 DES patients enrolled at (14%) patients d/c thienopyridine % Mortality Between 30 Days and 1 Year 19 sites • 68 (14%) patients d/c thienopyridine Factors associated with premature Thienopyridine discontinuation -older age -lower socioeconomic status -preexisting cardiovascular disease -inadequate discharge instructions -lack of referral to cardiac rehab HR=9. 0 P<0. 001 HR=1. 5 P=0. 08

Impact of Thrombus Burden on Risk of Stent Thrombosis With DES in Patients With STEMI Independent Predictors of ST Variable Hazard Ratio 95% CI Age 0. 6 0. 4 -0. 8 Index ST 6. 2 2. 1 -18. 9 Bifurcation 4. 1 1. 6 -10. 0 Thrombectomy 0. 1 0. 01 -0. 8 Large thrombus 8. 7 3. 4 -22. 5 Sianos G et al. J Am Coll Cardiol 2007; 50: 573 -83

Incomplete Stent Apposition in Patients With Acute MI: Drug-Eluting versus Bare Metal Stents van der Hoeven BL et al. JACC 2008; 51: 618 -26 Incomplete Stent Apposition (%) MISSION Trial: IVUS Results at 8 Months P<0. 001 P=0. 19

Outline • Introduction • Randomized clinical trials • Registry studies • The guidelines • Summary

Harmonizing Outcomes with Revascularization and Stents in AMI 3602 pts with STEMI with symptom onset ≤ 12 hours Aspirin, thienopyridine R 1: 1 UFH + GP IIb/IIIa inhibitor (abciximab or eptifibatide) Bivalirudin monotherapy (± provisional GP IIb/IIIa) Emergent angiography, followed by triage to… CABG – Primary PCI – Medical Rx 3006 pts eligible for stent randomization R 3: 1 Paclitaxel-eluting TAXUS stent Bare metal EXPRESS stent Clinical FU at 30 days, 6 months, 1 year, and then yearly through 5 years; angio FU at 13 months

One Year Composite Safety Endpoints* TAXUS (N=2257) EXPRESS (N=749) HR [95%CI] P Value Safety MACE** 8. 1% 8. 0% 1. 02 [0. 76, 1. 36] 0. 92 Death, all-cause 3. 5% 0. 99 [0. 64, 1. 55] 0. 98 - Cardiac 2. 4% 2. 7% 0. 90 [0. 54, 1. 50] 0. 68 - Non cardiac 1. 1% 0. 8% 1. 32 [0. 54, 3. 22] 0. 55 Reinfarction 3. 7% 4. 5% 0. 81 [0. 54, 1. 21] 0. 31 - Q-wave 2. 0% 1. 9% 1. 07 [0. 59, 1. 94] 0. 83 - Non Q-wave 1. 8% 2. 7% 0. 68 [0. 39, 1. 17] 0. 16 Stent thrombosis† 3. 2% 3. 4% 0. 93 [0. 59, 1. 47] 0. 77 - ARC definite 2. 6% 3. 0% 0. 88 [0. 54, 1. 43] 0. 60 - ARC probable 0. 5% 0. 4% 1. 33 [0. 38, 4. 73] 0. 65 1. 0% 0. 7% 1. 52 [0. 58, 4. 00] 0. 39 Stroke *Kaplan-Meier estimates; **Primary safety endpoint; †ARC definite or probable Stone GW, et al. N Engl J Med. 2009; 360: 1946 – 59.

Primary Efficacy Endpoint: Ischemic TLR 10 9 Ischemic TLR (%) TAXUS DES (n=2257) EXPRESS BMS (n=749) Diff [95%CI] = -3. 0% [-5. 1, -0. 9] 8 7 HR [95%CI] = 0. 59 [0. 43, 0. 83] 6 P=0. 002 7. 5% 5 4. 5% 4 3 2 1 0 0 Number at risk TAXUS DES 2257 EXPRESS BMS 749 1 2 3 4 5 6 7 8 9 10 11 12 Time in Months 2132 697 2098 675 2069 658 Stone GW, et al. N Engl J Med. 2009; 360: 1946 – 59. 1868 603

Multivariable Predictors of 1 -Year TLR (BMS Express patients, N=734) Variable Score HR (95% CI) P-value Total lesion length ≥ 40 mm 2 5. 28 [1. 73, 16. 15] 0. 004 Baseline RVD ≤ 3. 0 mm 1 3. 27 [1. 63, 6. 55] 0. 0008 Insulin-treated diabetes 1 3. 00 [1. 17, 7. 66] 0. 02 Lesion ulceration 1 3. 45 [1. 30, 9. 16] 0. 01 Killip class 2 -4 1 2. 50 [1. 20, 5. 20] 0. 01 Stone GW. ACC 2009.

1 -Year TLR According to BMS Risk Score (N=2915) N=946 (32. 5%) N=1520 (52. 1%) Stone GW. ACC 2009. N=449 (15. 4%)

Randomized Clinical Trials: DES vs BMS in STEMI Brar S, et al. J Am Coll Cardiol 2009; 53: 1677– 89

Randomized Clinical Trials: DES vs BMS in STEMI Mortality Brar S, et al. J Am Coll Cardiol 2009; 53: 1677– 89

Randomized Clinical Trials: DES vs BMS in STEMI Myocardial Infarction Brar S, et al. J Am Coll Cardiol 2009; 53: 1677– 89

Randomized Clinical Trials: DES vs BMS in STEMI Stent Thrombosis Brar S, et al. J Am Coll Cardiol 2009; 53: 1677– 89

Randomized Clinical Trials: DES vs BMS in STEMI TVR Brar S, et al. J Am Coll Cardiol 2009; 53: 1677– 89

Randomized Clinical Trials: DES vs BMS in STEMI Relationship Between Baseline Risk and Risk Difference for TVR in Randomized Trials A negative risk difference favors drug-eluting stents, whereas a positive risk difference favors BMS. The size of each circle relates to the weight of each trial. p 0. 001. Brar S, et al. J Am Coll Cardiol 2009; 53: 1677– 89

Outline • Introduction • Randomized clinical trials • Registry studies • The guidelines • Summary

Registry Studies: DES vs BMS in STEMI Brar S, et al. J Am Coll Cardiol 2009; 53: 1677– 89

Registry Studies: DES vs BMS in STEMI Brar S, et al. J Am Coll Cardiol 2009; 53: 1677– 89

Registry Studies: DES vs BMS in STEMI Brar S, et al. J Am Coll Cardiol 2009; 53: 1677– 89

Registry Studies: DES vs BMS in STEMI Brar S, et al. J Am Coll Cardiol 2009; 53: 1677– 89

Outline • Introduction • Randomized clinical trials • Registry studies • The guidelines • Summary

Guidelines With ST-Elevation Myocardial Infarction (Updating the 2004 Guideline and 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients Kushner et al, J. Am. Coll. Cardiol. 2009; 54; 2205 -2241;

Guidelines With ST-Elevation Myocardial Infarction (Updating the 2004 Guideline and 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients “The major advantage of DES over BMS is a small reduction in TVR rates. Given cost considerations, it could be argued that selective use of DES to prevent restenosis and TVR in high-risk patients (i. e. , patients with diabetes) and in high-risk lesions (longer and smaller diameter stents) could be recommended” Kushner et al, J. Am. Coll. Cardiol. 2009; 54; 2205 -2241;

Summary • The utilization of DES vs BMS in STEMI associated with – No difference in mortality, recurrent MI, or stent thrombosis – Reduction in TLR and restenosis, particularly those with high risk of BMS restenosis (>1 – diabetic, lesion > 40 mm, RVD < 3 mm, diabetes, and lesion ulceration) • Current guidelines suggest DES in STEMI IIa recommendation • Careful determination of ability to remain on dual anti-platelet therapy critical (compliance, upcoming surgery, bleeding, and associated anti-coagulant therapy) • Compulsive implantation technique, ensuring adequate vasodilator given to prevent undersizing of stent, particularly with DES given higher propensity for subsequent malapposition