Montalescot G - AIMRADIAL 2013 - Prasugrel and radial

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  • See page 2538 of 2010 ESC/EACTS guidelines on myocardial revascularizationSee page 2587 of 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention[source: page 3018 Hamm et al Eur Heart J 2011;32(23):2999-3054. ][source: page 665-666 Jneid et al J Am CollCardiol 2012;60(7):645-81. ]
  • tobacco, hypertension, hypercholesterolemia, brachial, prasugrel MD - removed
  • tobacco, hypertension, hypercholesterolemia, priorclopitreatment, brachial, prasugrel MD
  • tobacco, hypertension, hypercholesterolemia, priorclopitreatment, brachial, prasugrel MD
  • Montalescot G - AIMRADIAL 2013 - Prasugrel and radial

    1. 1. COI DISCLOSURE FOR DR. MONTALESCOT are available @ http://www.action-coeur.org
    2. 2. Clopidogrel Pretreatment
    3. 3. CURE Efficacy CREDO Efficacy CURE Safety* CREDO Safety** Yusuf S, et al. N Engl J Med 2001;345:494-502 Steinhubl SR, et al. JAMA 2002;288:2411-2420
    4. 4. CURE: Cardiovascular Death/Myocardial Infarction/Stroke During First 30 Days 25% NSTEMI (75% UA), ~21% revascularization Cumulative Hazard Rates 0.06 Placebo + Aspirin 0.05 0.04 Clopidogrel + Aspirin 0.03 RRR=21% 95% CI (0.67-0.92) p=0.003 0.02 0.01 0.0 0 Number: Placebo Clopidogrel 24-48h 6303 6259 10 20 30 Days of Follow-up 6108 6103 5998 6035 5957 5984 CURE Investigators. N Engl J Med 2001;345:494-502
    5. 5. CREDO: Effect of the Delay of Pre-treatment– 28 days P=0.020 for interaction between the delay of pretreatment and the protection against ischemic events Events (%) Pre-treatment- No Pren Clopidogrel treatment < 6 hrs 7.9 7.0 9.4 851 No-PT Better 893 6 to 24 hr * 5.8 PT-Clopidogrel Better RRR 38.6 P=0.05 RRR 18.5 P=0.23 Overall CREDO Results 0.4 -2 RRR -13.4 P=NS 0.6 0.8 1.0 1.2 Hazard ratio (95% CI) Placebo -3 -4 *Significant effect ≥ 15h after loading -5 Clopidogrel -6 0 5 10 15 20 25 30 Steinhubl SR, et al JAMA 2002;288:2411-2420 Steinhubl SR, et al. JACC 2006;47:939-943
    6. 6. PCI Pre-Treatment (With 300 mg load)  Events Trial CV Death or MI after PCI to 30 days OR (95% CI) PCI-CURE CREDO PCI-CLARITY Overall P=0.004 0.25 0.5 Favors Pre-treatment 1.0 2.0 Favors No Pre-treatment Sabatine. et al. JAMA. 2005;294:1224-1232
    7. 7. P2Y12 Pre-treatment Recommendations Title Citation Class LOE 2011 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation European Heart Journal 2011;32:2999–3054 “A P2Y12 inhibitor as soon as possible” Clopidogrel 600 mg Ticagrelor I A I I B B 2010 ESC/EACTS guidelines on myocardial revascularization European Heart Journal 2010;31:20:2501–2555 “Clopidogrel 600 mg as soon as possible” I C 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction Circulation 2012;126:875–910 “If invasive strategy, before PCI” Clopidogrel Ticagrelor *Prasugrel I I B B 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention Circulation 2011;124:e574–651 P2Y12 inhibitor Clopidogrel Prasugrel Ticagrelor I I I I A B B B * Prasugrel 60 mg may be considered for administration promptly upon presentation in patients with UA/NSTEMI for whom PCI is planned, before definition of coronary anatomy if both the risk for bleeding is low and the need for CABG is considered unlikely (Level of Evidence: IIb – C)
    8. 8. PRAGUE-8 - All Patients PRAGUE-8 - PCI Patients Widimsky P, et al. Eur Heart J 2008;29:1495-1503 ARMYDA-5 Efficacy ARMYDA-5 Safety Di Sciascio G, et al. J Am Coll Cardiol 2010;56:550-557
    9. 9. Death 1/204 1/164 13/933 18/1053 32/1313 0/103 1/513 66/4283 0/205 4/171 24/930 24/1063 31/1345 2/96 0/515 85/4325 Relative Weight [%] 3·03 [0·12-74·80] 1·0% 0·26 [0·03-2·32] 2·2% 0·53 [0·27-1·05] 23·2% 0·75 [0·41-1·40] 28·3% 1·06 [0·64-1·75] 43·1% 0·18 [0·01-3·85] 1·2% 3·02 [0·12-74·25] 1·0% 0·80 [0·57-1·11] 100% 105/3511 114/5087 219/8598 49/1515 14/832 63/2347 0·92 [0·65-1·30] 1·34 [0·77-2·34] 1·04 [0·74-1·46] 68·2% 31·8% 100% 13/923 209/4879 12/217 18/467 6/1481 76/4477 334/12444 19/990 110/1076 6/166 18/574 18/2679 12/332 183/5817 0·73 [0·36-1·49] 0·39 [0·31-0·50] 1·56 [0·57-4·25] 1·24 [0·64-2·41] 0·60 [0·24-1·52] 0·46 [0·25-0·86] 0·68 [0·42-1·09] 16·2% 24·0% 11·9% 17·0% 12·9% 17·8% 100% Events / Size, Clopidogrel Pretreatment No Pretreat Randomized CT ARMYDA5 Preload CIPAMI CLARITY PCI CREDO PCI CURE Davlouros et al. PRAGUE 8 All N=8,608 OR [CI 95%] OR=0·80 CI 95% [0·57-1·11] P=0·17 Observational from RCT ACUITY PCI REPLACE 2 All N=10,945 OR=1·04 CI 95% [0·74-1·46] P=0·83 Observational Amin et al. Dorler et al. Fefer et al. Feldman et al. Szuk et al. Chan et al. All N=18,261 OR=0·68 CI 95% [0·42-1·09] P=0·11 Pre-treatment better 0 No Pre-treatment better 0.5 1 1.5 2 2.5 3 3.5 4 Bellemain-Appaix A et al. JAMA 2012;308:2507-2516
    10. 10. PCI-NSTEACS Death Major Bleeding MACE Randomized CT CREDO PCI CURE All N=4 774 OR=0.93 CI 95% [0·63-1·36] p=0·69 OR=1·28 CI 95% [0·98-1·67] p=0·07 OR=0·75 CI 95% [0·64-0·87] p=0·0002 OR=1·19 CI 95% [0·90-1·58] p=0·22 OR=1.10 CI 95% [0·94-1·29] p=0·23 Observational from RCT ACUITY-PCI All N=5 026 OR=0·92 CI 95% [0·65-1·30] p=0·65 Observational Assali Feldman et al. TARGET All N=6 149 OR=0·58 CI 95% [0·23-1·48] p=0·26 All Studies N=15 949 0.01 OR=0·81 CI 95% [0·58-1·13] p=0·22 0.1 PreT better 1 No PreTt better 10 0.1 OR=0·89 CI 95% [0·48-1·65] p=0·72 OR=1·20 CI 95% [1·00-1·44] p=0·048 PreTt better 1 No PreTt better OR=0·86 CI 95% [0·59-1·25] p=0·43 OR=0·86 CI 95% [0·70-1·05] p=0·14 10 0.1 PreTt better 1 No PreTt better 10 Bellemain-Appaix A et al. ESC 2013. P4846
    11. 11. ACCOAST design NSTEMI + Troponin ≥ 1.5 times ULN local lab value Clopidogrel naive or on long term clopidogrel 75 mg Randomize 1:1 n~4100 (event driven) Double-blind Prasugrel 30 mg Coronary Angiography Coronary Angiography Prasugrel 30 mg Prasugrel 60 mg PCI CABG or Medical Management (no more prasugrel) Placebo PCI CABG or Medical Management (no prasugrel) Prasugrel 10 mg or 5 mg (based on weight and age) for 30 days 1° Endpoint: CV Death, MI, Stroke, Urg Revasc, GP IIb/IIIa inh. Bailout, at 7 days Montalescot G et al. Am Heart J 2011;161:650-656
    12. 12. Enrollment: >4,000 patients in 19 Countries Poland: 847 Sweden: 4 Canada: 146 Netherlands: 142 Belgium: 81 Portugal: 17 Germany: 529 France: 586 Czech Rep: 292 Austria: 172 Italy: 628 Finland: 42 Latvia: 5 Lithuania: 73 Slovakia: 47 Hungary: 134 Romania: 85 Turkey: 112 Israel: 131
    13. 13. Baseline Characteristics (I/III) Characteristics Age (mean, yrs) Female sex (%) Weight (mean, kg) BMI ≥ 30 (%) CV risk factors (%) Diabetes mellitus Dyslipidemia Hypertension Current smoker Region of enrolment (%) Eastern Europe/Israel Western Europe/Canada Pre-treatment No Pre-treatment (N =2037) 64 27 82 29 (N =1996) 64 28.0 82 28 20 45 63 34 20 45 61 33 42 58 42 58
    14. 14. Baseline Characteristics (II/III) Pre-treatment No Pre-treatment (N =2037) (N =1996) 76 24 34 78 22 34 14.6 15.2 4.4 4.2 Femoral 57 57 Radial 43 43 Characteristics GRACE score (%) <140 ≥140 CRUSADE score (median) Timing (hr) Symptom onset to 1st LD, median  1st LD to coronary angiogram, median Access (%)‖
    15. 15. Baseline Characteristics (III/III) Concomitant medications through 7 days (%) Aspirin, (%) Pre-treatment No Pre-treatment (N =2037) (N =1996) 98 98 65 29 0.8 4.7 55 84 90 14 69 30 66 31 0.6 3.3 56 84 90 12 72 27 Antithrombin Use, (%) UFH LMWH Bivalirudin Fondaparinux Proton pump inhibitor Beta blockers Statins ARBs ACE inhibitors Calcium channel blockers
    16. 16. Pharmacodynamic Sub-Study 350 Placebo LD1 Pre-treatment (30/30) No Pre-treatment (0/60) 60 mg LD2 *P<0.05 P2Y12 Reaction Units 300 250 Approximate time of PCI 200 150 100 30 mg LD1 * * 50 0 30 mg LD2 Pre LD1 Pre LD2 (baseline) 0.5 1 2 3 Hours (post LD2) Data presented as median ± SEM. * p<0.05 relative to the No pre-treatment group. LD = loading dose. Pretreatment=Prasugrel 30 mg/Prasugrel 30 mg; No Pre-treatment=Placebo/Prasugrel 60 mg 4 24
    17. 17. 1° Efficacy End Point @ 7 + 30 days (All Patients) 15 CV Death, MI, Stroke, UR, GPIIb/IIIa Bailout Pre-treatment 10.8 Endpoint (%) Pre-treatment 10.0 10 No Pre-treatment 10.8 No Pre-treatment 9.8 5 Hazard Ratio, 1.02 (95% 0.84, 1.25) P=0.81 Hazard Ratio, 0.997 (95% 0.83, 1.20) P=0.98 0 0 No. at Risk, Primary Efficacy End Point: No pre-treatment Pre-treatment 5 10 15 20 25 30 1752 1791 1621 1616 Days From First Dose 1996 2037 1788 1821 1775 1809 1769 1802 1762 1797
    18. 18. 1° Efficacy Endpoint (PCI Patients) CV Death, MI, Stroke, Urg Revasc, GP IIb/IIIa inh. bailout 20 CV Death, MI, Stroke, UR, GPIIb/IIIa Bailout PCI Cohort Endpoint (%) 15 Pre-treatment 13.1 No Pre-treatment 13.8 No Pre-treatment 13.1 10 Pre-treatment 14.1 HR, 1.03 (95% 0.84, 1.26) P=0.77 HR, 1.01 (95% 0.82, 1.24) P=0.93 5 0 0 No. at Risk, Efficacy End Point: No pre-treatment Pre-treatment 5 10 15 20 25 30 1177 1186 1177 1172 Days From First Dose 1372 1389 1191 1206 1187 1202 1183 1194 1179 1189
    19. 19. 1° Efficacy Endpoint Through 7 Days for Prespecified Subgroups (All Patients) Total Patients Pre-tx n (%) No Pre-tx n (%) Hazard Ratio (95% CI) 4033 203 (9.97) 195 (9.77) 1.02 (0.84, 1.25) PCI CABG Medical Management 2781 238 1014 185 (13.21) 9 (7.44) 9 (1.74) 181 (13.11) 8 (6.84) 6 (1.20) 1.01 (0.83, 1.25) 1.08 (0.42, 2.79) 1.45 (0.52, 4.09) 0.54 <75 years >75 years 3318 715 160 (9.62) 43 (11.53) 162 (9.79) 33 (9.65) 0.99 (0.79, 1.23) 1.20 (0.76, 1.88) 0.45 2923 1110 152 (10.24) 51 (9.24) 149 (10.36) 46 (8.24) 0.99 (0.79, 1.24) 1.14 (0.76, 1.70) 0.54 205 3824 7 (6.80) 195 (10.09) 12 (11.76) 183 (9.68) 0.56 (0.22, 1.43) 1.05 (0.86, 1.28) 0.20 820 3213 46 (11.14) 157 (9.67) 37 (9.09) 158 (9.94) 1.25 (0.81, 1.93) 0.97 (0.78, 1.21) 0.30 232 3801 11 (9.82) 192 (9.97) 13 (10.83) 182 (9.70) 0.91 (0.41, 2.03) 1.03 (0.84, 1.26) 0.76 1990 2008 84 (8.24) 119 (11.91) 105 (10.82) 90 (8.92) 0.76 (0.57, 1.01) 1.36 (1.03, 1.78) 0.004 1998 2003 120 (12.07) 82 (8.02) 109 (10.86) 86 (8.77) 1.13 (0.87, 1.46) 0.91 (0.67, 1.23) 0.30 3079 852 154 (10.05) 44 (9.73) 143 (9.24) 47 (11.75) 1.09 (0.87, 1.37) 0.82 (0.55, 1.24) 0.24 2276 1711 125 (10.96) 76 (8.75) 111 (9.77) 83 (9.86) 1.14 (0.88, 1.47) 0.88 (0.64, 1.20) 0.21 1692 2341 66 (7.65) 137 (11.67) 63 (7.60) 132 (11.31) Overall (pre-treatment vs. no pre-treatment) Interaction P-value† Age Sex Male Female Weight <60 kg >60 kg Diabetes Yes No Prior clopidogrel treatment Yes No Time from Sx to LD <median >median Time from first LD to angio/PCI <median >median GRACE score <140 >140 Access Femoral Radial Region Eastern Europe/Israel Western Europe/Canada 0.1 0.2 0.5 Pre-treatment better 1 2 5 No pre-treatment better *Hazard ratio not evaluated for <10 events. †Interaction p-value is from a Cox proportional hazards model with treatment, subgroup, and the treatment-by-subgroup interaction as fixed effects; PCI includes 11 patients with PCI + CABG. 1.02 (0.72, 1.43) 0.93 1.03 (0.81, 1.31)
    20. 20. All TIMI (CABG or non-CABG) Major Bleeding (All Treated patients) 5 Hazard Ratio, 1.90 (95% 1.19, 3.02) P=0.006 Hazard Ratio, 1.97 (95% 1.26, 3.08) P=0.002 Endpoint (%) 4 Pre-treatment 2.9 3 Pre-treatment 2.6 2 All TIMI Major Bleeding 1 No Pre-treatment 1.5 0 No Pre-treatment 1.4 0 No. at Risk, All TIMI Major Bleeding: No pre-treatment Pre-treatment 5 10 15 20 25 30 1284 1297 1263 1280 Days From First Dose 1996 2037 1947 1972 1328 1339 1297 1310 1288 1299
    21. 21. All TIMI (CABG or Non-CABG) Major Bleeding (PCI Patients) 5 Endpoint (%) 4 3 HR, 2.69 (95% 1.13, 6.40) P=0.02 All TIMI Major Bleeding PCI Cohort HR, 2.65 (95% 1.23, 5.70) P=0.010 2 Pre-treatment 1.4 Pre-treatment 1.7 1 No Pre-treatment 0.5 No Pre-treatment 0.7 0 0 No. at Risk, All TIMI Major Bleeding: No pre-treatment Pre-treatment 5 10 15 20 25 30 1268 1280 1249 1269 Days From First Dose 1372 1389 1356 1364 1302 1314 1280 1293 1272 1282
    22. 22. All TIMI Major Bleeding for Prespecified Subgroups Through 7 days (All Treated Patients) Total Patients Pre-tx (%) No Pre-tx (%) Overall (pre-treatment vs. no pre-treatment) Hazard Ratio Interaction (95% CI) P-value† 52 (2.55) 27 (1.35) 1.90 (1.19, 3.02) 2781 238 1014 22 (1.57) 11 (0.80) 25 (20.66) 16 (13.68) 5 (0.97) 0 (0.00) 1.98 (0.96, 4.09) 1.59 (0.85, 2.98) NE 0.74 <75 years >75 years Age 4033 PCI CABG Medical Management* 3318 715 36 (2.16) 16 (4.29) 22 (1.33) 5 (1.46) 1.64 (0.96, 2.78) 2.95 (1.08, 8.05) 0.31 2923 1110 31 (2.09) 21 (3.80) 21 (1.46) 6 (1.08) 1.43 (0.82, 2.49) 3.61 (1.46, 8.95) 0.09 205 3824 5 (4.85) 47 (2.43) 1 (0.98) 26 (1.37) NE 1.78 (1.10, 2.87) 0.35 820 3213 6 (1.45) 46 (2.83) 6 (1.47) 21 (1.32) 0.98 (0.32, 3.05) 2.16 (1.29, 3.62) 0.22 1990 2008 28 (2.75) 24 (2.40) 18 (1.86) 9 (0.89) 1.50 (0.83, 2.71) 2.70 (1.25, 5.80) 0.23 1998 2003 27 (2.72) 24 (2.35) 12 (1.20) 15 (1.53) 2.28 (1.16, 4.51) 1.54 (0.81, 2.93) 0.41 2051 1789 23 (2.23) 27 (2.97) 10 (0.98) 2.29 (1.09, 4.81) 15 (1.71) 1.75 (0.93, 3.28) 0.59 3079 852 34 (2.22) 16 (3.54) 18 (1.16) 8 (2.00) 1.92 (1.09, 3.41) 1.76 (0.75, 4.12) 0.87 2276 1711 29 (2.54) 22 (2.53) 18 (1.58) 8 (0.95) 1.62 (0.90, 2.91) 2.67 (1.19, 6.00) 0.66 1692 2341 14 (1.62) 38 (3.24) 5 (0.60) 22 (1.89) 2.69 (0.97, 7.47) 1.74 (1.03, 2.94) 0.46 Sex Male Female Weight <60 kg* >60 kg Diabetes Yes No Time from Sx to LD <median >median Time from first LD to angio/PCI <median >median CRUSADE score‡ <median >median GRACE score <140 >140 Access Femoral Radial Region Eastern Europe/Israel Western Europe/Canada 0.2 0.5 Pre-treatment better 1 2 5 10 15 No pre-treatment better *Hazard ratio not evaluated for <10 events. †Interaction p-value is from a Cox proportional hazards model with treatment, subgroup, and the treatment-by-subgroup interaction as fixed effects; ‡CRUSADE score is a post-hoc analysis; PCI includes 11 patients with PCI + CABG.
    23. 23. % radial access / country 50% Germany Austria Israel Belgium Netherlands Poland Canada Romania Czech Republic Italy 6 12 32 33 33 33 39 42 45 45 Lithuania Finland Hungary France 79 85 90 92
    24. 24. 5 (0.97) 0 (0.00) 1014 2781 22 (1.57) 11 (0.80) 36 (2.16) 22 (1.33) 3318 36 (2.16) 22 (1.33) 3318 25 (20.66) 16 (13.68) 238 16 (4.29) 5 (1.46) 5 (1.46) 715 16 (4.29) 715 5 (0.97) 0 (0.00) 1014 2923 31 (2.09) 21 (1.46) 2923 31 (2.09) 21 (1.46) 3318 36 (2.16) 22 (1.33) 21 (3.80) 6 (1.08) 6 (1.08) 1110 16 (4.29) 1110 21 (3.80) 5 (1.46) 715 NE 1.98 (0.96, 4.09) 1.64 (0.96, 2.78) 1.64 (0.96, 2.78) 1.59 (0.85, 2.98) 2.95 (1.08, 8.05) 2.95 (1.08, 8.05) NE 1.43 (0.82, 2.49) 1.43 (0.82, 2.49) 1.64 (0.96, 2.78) 3.61 (1.46, 8.95) 3.61 (1.46, 8.95) 2.95 (1.08, 8.05) Radial vs. Femoral 0.74 0.31 0.31 0.09 0.09 0.31 205 205 2923 3824 3824 1110 5 (4.85) 5 (2.09) 31(4.85) 47(3.80) 47 (2.43) 21 (2.43) 1 (0.98) 1 (1.46) 21(0.98) 26(1.37) 26(1.08) 6 (1.37) NE NE 1.43 (0.82, 2.49) 1.78(1.46, 8.95) (1.10,2.87) 1.78 3.61 (1.10, 2.87) 0.35 0.35 0.09 820 820 205 3213 3213 3824 1990 1990 820 2008 2008 3213 1998 1998 1990 2003 2003 2008 6 (1.45) 6 (1.45) 5 (4.85) 46(2.83) (2.83) 46 (2.43) 47 28(2.75) (2.75) 28(1.45) 6 (2.40) 24(2.40) 24 (2.83) 46 27 (2.72) 27 (2.72) 28 (2.75) 24 (2.35) 24 (2.35) 24 (2.40) 6 (1.47) 6 (1.47) 1 (0.98) 21(1.32) (1.32) 21 (1.37) 26 18 (1.86) 18(1.47) 6 (1.86) 9 9 (0.89) 21(0.89) (1.32) 12(1.20) (1.20) 12 (1.86) 18 (1.53) 15 15(0.89) 9 (1.53) 0.98 (0.32, 3.05) 0.98 (0.32, 3.05) NE 2.16 (1.29, 3.62) 2.16 (1.29, 3.62) 1.78 (1.10, 2.87) 1.50 (0.83, 2.71) 1.50 (0.83, 2.71) 0.98 (0.32, 3.05) 2.70 (1.25, 5.80) 2.70 (1.25, 5.80) 2.16 (1.29, 3.62) 2.28 (1.16, 4.51) 2.28 (1.16, 4.51) 1.50 (0.83, 2.71) 1.54 (0.81, 2.93) 1.54 (0.81, 2.93) 2.70 (1.25, 5.80) 0.22 0.22 0.35 2051 2051 1998 1789 1789 2003 3079 3079 2051 852 852 1789 2276 2276 3079 1711 1711 852 23 (2.23) 23 (2.23) 27 (2.72) 27 (2.97) 27 (2.97) 24 (2.35) 34 (2.22) 34 (2.22) 23 (2.23) 16 (3.54) 16 (3.54) 27 (2.97) 29 (2.54) 29 (2.54) 34 (2.22) 22 (2.53) 22 (2.53) 16 (3.54) 10 (0.98) 2.29 (1.09, 4.81) 0.59 0.59 10 (0.98) 2.29 (1.09, 4.81) 12 (1.20) 2.28 (1.16, 4.51) 0.41 15(1.71) 1.75 (0.93, 3.28) (1.71) 1.75 (0.93, 3.28) 15 (1.53) 1.54 (0.81, 2.93) 18 (1.16) 1.92 (1.09, 3.41) 0.87 0.87 18 (1.16) 1.92 (1.09, 3.41) 10 (0.98) 2.29 (1.09, 4.81) 0.59 1.76 (0.75, 4.12) 8 (2.00) 8 (1.71) 1.76 (0.75, 4.12) 15(2.00) 1.75 (0.93, 3.28) 18 (1.58) 1.62 (0.90, 2.91) 0.66 0.66 HR 18 (1.58) 1.62 (0.90, 2.91) Int. p 18 (1.16) 1.92 (1.09, 3.41) 2.67 (1.19, 6.00) 0.87 8(0.95) (0.95) 2.67 (1.19, 6.00) 8 (2.00) 1.76 (0.75, 4.12) 8 1692 2276 1692 1711 2341 2341 14 (1.62) 29 (2.54) 14 (1.62) 22 (2.53) 38 (3.24) 38 (3.24) 5 (0.60) 18(0.60) 5 (1.58) 8 (0.95) 22 (1.89) 22 (1.89) 2.69 (0.97, 7.47) 1.62 (0.90, 2.91) 2.69 (0.97, 7.47) 2.67 (1.19, 6.00) 1.74 (1.03, 2.94) 1.74 (1.03, 2.94) 0.46 0.66 0.46 5 (0.60) 22 (1.89) 2.69 (0.97, 7.47) 1.74 (1.03, 2.94) 0.46 Radial vs. femoral: 61% lower incidence of TIMI major bleeding not related to CABG CI CI CI 0.23 0.23 0.22 0.41 0.41 0.23 All TIMI Major Bleeding (All treated patients) FEMORAL RADIAL 0.2 0.2 0.5 0.5 1 1 2 2 5 5 Pre-treatment better Pre-treatment better 1 0.2 0.5 No pre-treatment better 2 No pre-treatment better 5 Pre-treatment better No pre-treatment better 14 10 1692 15 (1.62) 10 15 2341 38 (3.24) 10 15
    25. 25. Non-CABG TIMI Major Bleeding Endpoints Through 7 Days (All Treated Patients) 3,0 Pre-treatment (N=2037) Most Frequent Locations of Major Bleed No Pre-treatment (N=1996) Event Rate (%) 2,5 2,0 P=0.003 1,5 1,33 P=0.002 1,0 0,83 P not evaluable 0,45 0,5 0,05 0 0,15 0,0 N= 27 9 Non-CABG TIMI Major Bleeding 1 0 Fatal Bleeding 17 3 Life Threatening Bleeding
    26. 26. Conclusions ● In NSTE-ACS patients managed invasively within 48 hours of admission, pre-treatment with prasugrel does not reduce major ischemic events through 30 days but increases major bleeding complications. ● The results are consistent among patients undergoing PCI supporting treatment with prasugrel once the coronary anatomy has been defined. ● No subgroup appears to have a favorable risk/benefit ratio of pre-treatment. ● Reappraisal of routine pre-treatment strategies in NSTEACS is needed.

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