Stent Parameters Predict Major Adverse Clinical Events and the Response to Platelet Glycoprotein IIb/IIIa Blockade Findings of the ESPRIT Trial James E. Tcheng, MD; Ing Haan Lim, MBBS; Shankar Srinivasan, PhD; Joseph Jozic, MD; C. Michael Gibson, MS, MD; J. Conor O’Shea, MD; Joseph A. Puma, MD; Daniel I. Simon, MD Circulation Cardiovascular Interventions. 2009;2:43-51

Stent Parameters and MACE n Post-hoc analysis of the 1983 pts in ESPRIT receiving a stent n MACE (48 hr, 1 yr) by nominal stent parameters l Number of stents implanted (1, 2, >3) l Total length of stent (quartiles of mm) l Stent diameter ( mm) l Stented vessel area (quartiles of mm 2 ) n Analysis by randomization l Placebo versus eptifibatide Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

eptifibatide µg/kg bolus (boluses 10 min apart) 2.0 µg/kg-min infusion x18-24° + heparin 60 U/kg bolus (ACT sec) eptifibatide µg/kg bolus (boluses 10 min apart) 2.0 µg/kg-min infusion x18-24° + heparin 60 U/kg bolus (ACT sec) placebo (bailout permitted) + heparin 60 U/kg bolus (ACT sec) placebo (bailout permitted) + heparin 60 U/kg bolus (ACT sec) vs.vs. Study Design ASA, thienopyridine pre-rx; randomization in cath lab elective (non-urgent) stent PCI 48 hour, 30 day, 6 month, 1 year follow-up primary endpoint: 48° death, MI, urg revasc, thrombotic bailout elective (non-urgent) stent PCI 48 hour, 30 day, 6 month, 1 year follow-up primary endpoint: 48° death, MI, urg revasc, thrombotic bailout O’Shea JC et al., Am Heart J. 2000;140:834–839

Primary Endpoint Analysis Events to 48 Hours  52% p=0.029  52% p=0.029  40% p=NS  40% p=NS  33% p=0.064  33% p=0.064  40% p=  40% p=  37% p=  37% p= (MB >5x) n=2064  50% p=NS  50% p=NS ESPRIT Investigators. Lancet. 2000;356:2037–2044

Efficacy by Clinical Syndrome 30 Day death, MI, urgent TVR, bailout IIb/IIIa  50% p=0.034 NNT=14  50% p=0.034 NNT=14  41% p=0.028 NNT=18  41% p=0.028 NNT=18  23% p=0.30  23% p=0.30  44% p=NS NNT=11  44% p=NS NNT=11  31% p=NS  31% p=NS n=794 (38%) n=664 (32%) n=279 (14%) n=93 (5%) n=187 (9%) Puma JA et al. J Am Coll Cardiol. 2006;47:715–718.

Death, MI, urgent TVR Number of stents 40% 30% 20% 10% 0 12≥3 P=0.001 MACE at 48º by Number of Stents Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51 Eptifibatide Placebo

<1515 to <18 mm18 to <30 mm P=0.030 ≥30 mm P=0.003 MACE at 48º by Stent Length 40% 30% 20% 10% 0 Eptifibatide Placebo Total length of implanted stent(s) Death, MI, urgent TVR Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

≤2.5 mm>2.5 to <3.5 mm≥3.5 mm P= % 30% 20% 10% 0 Eptifibatide Placebo Death, MI, urgent TVR Stent diameter MACE at 48º by Stent Diameter Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

< to < to <292≥292 P=0.039 P= % 30% 20% 10% 0 Eptifibatide Placebo MACE at 48º by Stented Vessel Area Death, MI, urgent TVR Stented vessel area (mm 2 ) Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

Total stent length (mm) Mean stent diameter (mm) Stent Diameter vs. Length Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

12≥3 P= % 30% 20% 10% 0 Eptifibatide Placebo MACE at 1 year by Number of Stents Death, MI, TVR Number of stents Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

P=0.034 P=0.024 <1515 to <18 mm18 to <30 mm≥30 mm 40% 30% 20% 10% 0 Eptifibatide Placebo MACE at 1 year by Stent Length Death, MI, TVR Total length of implanted stent(s) Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

≤2.5 mm>2.5 to <3.5 mm≥3.5 mm P= % 30% 20% 10% 0 Eptifibatide Placebo MACE at 1 year by Stent Diameter Death, MI, TVR Stent diameter Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

< to < to <292≥292 P= % 30% 20% 10% 0 Eptifibatide Placebo MACE at 48º by Stented Vessel Area Death, MI, TVR Stented vessel area (mm 2 ) Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

Eptifibatide Better Placebo Better Number of Stents 1 2 ≥3 Stent Length (mm) <15 15 – <18 18 – <30 ≥30 Stent Diameter (mm) ≤2.5 >2.5 – <3.5 ≥3.5 Stented Vessel Area (mm 2 ) < – < – <292 ≥292 Odds Ratios of MACE at 48º Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

Number of Stents 1 2 ≥3 Stent Length (mm) <15 15 – <18 18 – <30 ≥30 Stent Diameter (mm) ≤2.5 >2.5 – <3.5 ≥3.5 Stented Vessel Area (mm 2 ) < – < – <292 ≥292 Eptifibatide Better Placebo Better Odds Ratios of MACE at 1 year Tcheng JE et al. Circ Cardiovasc Intervent; 2009; 2:43-51

Stent Parameters and MACE n In the placebo group, MACE rates increased as the number of stents increased, with increasing total length of stent, and with total stented vessel area l relationship nearly linear with total stented vessel area n Risk gradient significantly flattened by eptifibatide n Eptifibatide had significant efficacy with: l >2 stents l >18 mm total stent length