The Additive Value of Tirofiban Administered With

Department of Cardiology University of Ferrara M. Valgimigli University of Ferrara Italy Erasmus MC, Thoraxcenter The Netherlands The Additive Value of Tirofiban Administered With the High-Dose Bolus in the Prevention of Ischemic Complications During High-Risk Coronary Angioplasty The ADVANCE Trial

p = 0.002 8,5 p = 0.32 5,8 5,6 4,5 acs pts non acs pts 30-day composite events (death, MI, urgent TVR) by clinical status Tirofiban p = 0.032 9,0 Abciximab 7,59 8,0 7,0 6,01 6,0 5,0 4,0 3,0 2,0 1,0 0,0 all pts

Dr Schneider’s Hypothesis • Baseline platelet reactivity is not uniform in patients undergoing PCI • The higher the baseline value, the worse the outcome • Baseline platelet reactivity is proportional to the clinical status, lower in elective pts, higher in NSTEACS and highest in STEMI pts • Tirofiban, at Restore regimen, is just enough, soon after the bolus, to control platelet reactivity in elective patients Circ 01; 104: 18; AJC 02; 90: 1421; AJC 03; 91: 334; AJC 03; 91: 872; Frossard Circ 04; 110

AIM • To re-assess the efficacy of Tirofiban when given at SHDB on top of ADP receptor blockers in: • Elective patients • NSTE-ACS patients

AIM • To re-assess the efficacy of Tirofiban when given at SHDB on top of ADP receptor blockers in High-Risk: • Elective patients • Multivessel treatment • Diabetes • NSTE-ACS patients • High-risk features (ESC guidelines)

PCI Indications ACS Silent Ischemia Viability SA

NSTE-ACS Population (n=111) 79% • 73% Troponin positive • 55% ST >0.5 mm 2 leads • 23% Diabetes

Study Protocol 160-325mg ASA 500mg ticlidopine bolus + 250mg bid or 300mg clopidogrel bolus + 75mg daily 100U/kg bolus UFH + Bolus to maintain 300s ACT 50-70U/kg bolus UFH + Bolus to maintain 200s ACT Placebo 25mcg/kg bolus tirofiban + 0.15mcg/kg/min infusion for 24-48 hours Valgimigli et al. (2004) JACC 44:14-19

Primary Endpoint Death, nonfatal MI, TVR and thrombotic bailout GP IIb/IIIa Secondary Endpoints Each component of the primary endpoint Effect of drug on troponin I levels Effects in prespecified subgroups Diabetics Patients with ACS TIMI major and minor bleeding Endpoints ≈199 Patients 30% events Controls 40% events reduction β-error 0.8 α-error .05 Valgimigli et al. (2004) JACC 44:14-19

Characteristics Placebo (n=101) HDB Tirofiban (n=101) P-Value Age (yr) 687 699 NS Male sex (%) 66 69 NS Diabetes (%) 45 53 NS 15 19 NS Previous PCI (%) 45 50 NS Pervious MI (%) 21 19 NS Creatinine (mg/dl) 1.10.3 1.00.2 NS Baseline Characteristics Heart failure (%) Valgimigli et al. (2004) JACC 44:14-19

1° End-point 100 90 20% 80 P=0,01 70 35% 60 Tirofiban SHDB Suirvival Probability % Placebo 50 40 30 20 10 0 0 50 100 150 200 250 300 350 400 Days Valgimigli et al. (2004) JACC 44:14-19

Clinical Outcome 0.01 0.048 n.s. % 0.052 n.s. TVR 1°Endpoint MI MACE Death Valgimigli et al. (2004) JACC 44:14-19

Troponin I and CK-MB P<0. 01 P=0.001 ng/ml Troponin I CK-MB Valgimigli et al. (2004) JACC 44:14-19

Subgroup Analysis Acute Coronary Syndrome Yes No Diabetes Yes No 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 Tirofiban Better Placebo Better Valgimigli et al. (2004) JACC 44:14-19

Safety Results • No incidence of major bleeding • No RBC transfusions • No severe thrombocytopenia • One mild thrombocytopenia in each group Placebo 20 Tirofiban 18 16 14 P=0.19 12 10 # Patients 8 6 4 2 0 Minor Bleeding Valgimigli et al. (2004) JACC 44:14-19

CONCLUSIONS • Tirofiban when given at SHDB, immediately before high-risk PCIs, to patients who have been pre-treated with thienopyridines was: • As safe as • More effective than UFH alone in the prevention of periprocedural ischemic complications • Our current findings, based on a limited and selected sample size, should be viewed as preliminary, thus giving input for further research in this field. Valgimigli et al. (2004) JACC 44:14-19

The Additive Value of Tirofiban Administered With