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 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 M. Valgimigli University of Ferrara Italy Erasmus MC, Thoraxcenter The Netherlands Department of Cardiology University of Ferrara

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

Department of Cardiology, University of Ferrara, Italy 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

Department of Cardiology, University of Ferrara, Italy AbciximabEptifibatide Tirofiban PRISM Tirofiban RESTORE 10ug/kg in 3’ 15’ P<0,02 COMPARE, Circulation % Aggregation The COMPARE Trial Only ACS patients elegibile The COMPARE Trial Only ACS patients elegibile

Department of Cardiology, University of Ferrara, Italy AIM To re-assess the efficacy of Tirofiban when given at SHDB on top of ADP receptor blockers in: I. Elective patients II. NSTE-ACS patients

Department of Cardiology, University of Ferrara, Italy AIM To re-assess the efficacy of Tirofiban when given at SHDB on top of ADP receptor blockers in : To re-assess the efficacy of Tirofiban when given at SHDB on top of ADP receptor blockers in High-Risk: I. Elective patients i.Multivessel treatment ii.Diabetes II. NSTE-ACS patients i.High-risk features (ESC guidelines)

Department of Cardiology, University of Ferrara, Italy PCI Indications ACS SA Silent Ischemia Viability

Department of Cardiology, University of Ferrara, Italy NSTE-ACS Population (n=111) 73% Troponin positive 55% ST >0.5 mm  2 leads 23% Diabetes 79%

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

Department of Cardiology, University of Ferrara, Italy Endpoints 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 ≈199 Patients 30% events Controls 40% events reduction β-error 0.8 α-error.05 Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy Baseline Characteristics Characteristics Placebo (n=101) HDB Tirofiban (n=101) P- Value Age (yr) 68  769  9 NS Male sex (%) 6669NS Diabetes (%) 4553NS 1519NS Previous PCI (%) 4550NS Pervious MI (%) 2119NS Creatinine (mg/dl) 1.1   0.2 NS Heart failure (%) Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy Baseline Characteristics Characteristics Placebo (n=101) HDB Tirofiban (n=101) P- Value Age (yr) 68  769  9 NS Male sex (%) 6669NS Diabetes (%) 4553NS 1519NS Previous PCI (%) 4550NS Pervious MI (%) 2119NS Creatinine (mg/dl) 1.1   0.2 NS Heart failure (%) Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy Baseline Characteristics Characteristics Placebo (n=101) HDB Tirofiban (n=101) P- Value Age (yr) 68  769  9 NS Male sex (%) 6669NS Diabetes (%) 4553NS 1519NS Previous PCI (%) 4550NS Pervious MI (%) 2119NS Creatinine (mg/dl) 1.1   0.2 NS Heart failure (%) Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy Baseline Characteristics Characteristics Placebo (n=101) HDB Tirofiban (n=101) P- Value Age (yr) 68  769  9 NS Male sex (%) 6669NS Diabetes (%) 4553NS 1519NS Previous PCI (%) 4550NS Pervious MI (%) 2119NS Creatinine (mg/dl) 1.1   0.2 NS Heart failure (%) Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy Baseline Characteristics Characteristics Placebo (n=101) HDB Tirofiban (n=101) P- Value Age (yr) 68  769  9 NS Male sex (%) 6669NS Diabetes (%) 4553NS 1519NS Previous PCI (%) 4550NS Pervious MI (%) 2119NS Creatinine (mg/dl) 1.1   0.2 NS Heart failure (%) Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy Baseline Characteristics Characteristics Placebo (n=101) HDB Tirofiban (n=101) P- Value Age (yr) 68  769  9 NS Male sex (%) 6669NS Diabetes (%) 4553NS 1519NS Previous PCI (%) 4550NS Pervious MI (%) 2119NS Creatinine (mg/dl) 1.1   0.2 NS Heart failure (%) Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy Baseline Characteristics Characteristics Placebo (n=101) HDB Tirofiban (n=101) P- Value Age (yr) 68  769  9 NS Male sex (%) 6669NS Diabetes (%) 4553NS 1519NS Previous PCI (%) 4550NS Pervious MI (%) 2119NS Creatinine (mg/dl) 1.1   0.2 NS Heart failure (%) Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy Baseline Characteristics Characteristics Placebo (n=101) HDB Tirofiban (n=101) P- Value Age (yr) 68  769  9 NS Male sex (%) 6669NS Diabetes (%) 4553NS 1519NS Previous PCI (%) 4550NS Pervious MI (%) 2119NS Creatinine (mg/dl) 1.1   0.2 NS Heart failure (%) Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy 1 ° End-point Suirvival Probability % 20% 35% P=0, Days Tirofiban SHDB Placebo Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy Clinical Outcome % 1°Endpoint MACE Death MI TVR n.s Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy Troponin I and CK-MB P=0.001 P<0. 01 Troponin ICK-MB ng/ml Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy Subgroup Analysis Tirofiban BetterPlacebo Better Acute Coronary Syndrome Yes No Diabetes Yes No Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy Safety Results No incidence of major bleeding No RBC transfusions No severe thrombocytopenia One mild thrombocytopenia in each group Minor Bleeding Placebo Tirofiban P=0.19 # Patients Valgimigli et al. (2004) JACC 44:14-19

Department of Cardiology, University of Ferrara, Italy 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 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