A Large Prospective Randomized Trial of DES vs BMS in Patients with STEMI

Transcription

1 HORIZONS-AMI: A Large Prospective Randomized Trial of DES vs BMS in Patients with STEMI Gregg W. Stone MD Columbia University Medical Center Cardiovascular Research Foundation

2 Disclosures Gregg W. Stone Research support from The Medicines Company, Boston Scientific and Abbott Vascular

3 The 1 st Debate: Treatment of Acute Coronary Thrombosis and STEMI rt-pa PTCA

4 23 Randomized Trials of PCI vs. Lysis N = 7,739 p= P< P< p= Death Reinfarction Hemorrhagic stroke Total stroke Keeley, Grines. Lancet 2003;361:13-20

5 13 RCTs of BMS vs. Balloon PTCA in AMI N=6, day events Bare metal stents Balloon angioplasty RR [95% CI] RR [95% CI] 0.97 [0.74, P Value Mortality 2.9% 3.0% ] 0.92 Reinfarction 2.0% 2.2% 0.61 [0.66, 1.27] 0.60 TVR 3.1% 5.1% [0.47, 0.77] 6-12 month events 0.98 [0.79, Mortality 5.1% 5.2% ] Reinfarction 3.7% 3.9% 0.94 [0.74, 1.20] TVR 11.3% 18.4% < [0.55, 0.69] BMS better PTCA better De Luca G et al. Int J Cardiol ;119:

6 Massachusetts State Registry 2-year mortality (propensity adjusted) in 1298 matched pairs (2596 pts) with STEMI at 21 hospitals between 4/03 9/04 Death (adjusted) (%) % mortality at 30 days! 3% mortality at 1-year! 1 BMS (n=1298) DES (n=1298) P= % 8.5% Days after Initial Procedure Drug-Eluting Stent No. at risk Cum. incidence (%) Bare-Metal Stent No. at risk Cum. incidence (%) Mauri L et al. NEJM 2008;359:

7 11 DES vs. BMS RCTs in AMI (n=3,607) Death at 12 Months Study DES n/n BMS n/n OR (fixed) 95% CI Weight % OR (fixed) 95% CI DiLorenzo et al 7/180 6/ [0.18, 1.74] BASKET-AMI 6/143 6/ [0.15, 1.60] DEDICATION 16/313 8/ [0.87, 4.87] Diaz de la Llera et al 3/60 2/ [0.22, 8.52] HAAMU-STENT 8/82 4/ [0.61, 7.30] MISSION 2/158 4/ [0.09, 2.63] PASSION 16/310 20/ [0.40, 1.55] SELECTION 1/40 3/ [0.03, 3.18] SESAMI 3/160 6/ [0.12, 2.00] STRATEGY 7/87 8/ [0.30, 2.53] TYPHOON 8/355 8/ [0.37, 2.71] Total (95% CI) 77/ / % 4.4% Test for heterogeneity: I 2 = 0% Favors DES Favors BMS [0.66, 1.27] P=0.59 De Luca G et al. Int J Cardiol 2008

8 11 DES vs. BMS RCTs in AMI (n=3,607) TVR at 12 Months Study DES n/n BMS n/n OR (fixed) 95% CI Weight % OR (fixed) 95% CI DiLorenzo et al 7/180 14/ [0.09, 0.57] BASKET-AMI 10/143 9/ [0.21, 1.40] DEDICATION 16/313 41/ [0.20, 0.65] Diaz de la Llera et al 0/60 3/ [0.01, 2.41] HAAMU-STENT 3/82 8/ [0.09, 1.37] MISSION 5/158 17/ [0.09, 0.72] PASSION 16/310 23/ [0.35, 1.31] SELECTION 2/40 13/ [0.02, 0.52] SESAMI 7/160 20/ [0.13, 0.78] STRATEGY 8/87 21/ [0.13, 0.78] TYPHOON 20/355 48/ [0.22, 0.66] Total (95% CI) 94/ / Test for heterogeneity: I 2 = 0% 5.0% 12.6% = 7.6% Favors DES Favors BMS 0.36 [0.28, 0.47] P< De Luca G et al. Int J Cardiol 2008

9 DES in AMI: The TYPHOON Trial Primary Endpoint (TVF*) Through 360 Days TVF (%) SES BMS Routine Angio FU Time (days) 49% P = * Defined as target vessel-related cardiac death, ReMI or ischemia driven TVR Spaulding C et al. NEJM 2006;355:

10 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

11 HORIZONS: 30 Day Adverse Events P<0.001 P = 0.90 P = *Not related to CABG ** Plat cnt <100,000 cells/mm 3 Stone GW et al. NEJM 2008;358:

12 HORIZONS: 1-Year All-Cause Mortality 5 Bivalirudin alone (n=1800) Heparin + GPIIb/IIIa (n=1802) 4.8% Mortality (%) Number at risk Bivalirudin alone Heparin+GPIIb/IIIa % 2.1% = 1.0% P= Time in Months = 1.4% 3.4% Diff [95%CI] = -1.5% [-2.8,-0.1] HR [95%CI] = 0.69 [0.50, 0.97] P=0.029 Stone GW et al. NEJM 2008;358: Stone GW. TCT 2008

13 Harmonizing Outcomes with Revascularization and Stents in AMI Primary Medical Rx 193 Primary CABG 62 Deferred PCI 2 Index PCI, not eligible - PTCA only Stented % of all stented pts were randomized 3602 pts with STEMI R 3:1 R 1: pts eligible for stent rand. UFH + GPI (n=1802) Bivalirudin (n=1800) Randomized TAXUS DES N=2257 EXPRESS BMS N= Withdrew Lost to FU year FU N=2186 (96.9%) N=715 (95.5%)

14 One-Year All-Cause Mortality 5 TAXUS DES (n=2257) EXPRESS BMS (n=749) Mortality (%) % 3.5% HR [95%CI] = 0.99 [0.64,1.55] P= Number at risk TAXUS DES EXPRESS BMS Time in Months Stone GW. In press.

15 Stent Thrombosis (%) Number at risk PES BMS Stent Thrombosis (ARC Definite or Probable) Paclitaxel-eluting stents (n=2238) Bare metal stents (n=744) Time in Months Stone GW. In press. HR [95%CI] = 0.93 [0.59,1.47] P= % 3.2%

16 Primary Efficacy Endpoint: Ischemic TLR Ischemic TLR (%) Number at risk TAXUS DES EXPRESS BMS Diff [95%CI] = -3.0% [-5.1,[ -0.9] HR [95%CI] = 0.59 [0.43, 0.83] P= Time in Months TAXUS DES (n=2257) EXPRESS BMS (n=749) % 4.5% Stone GW. In press.

17 Binary Analysis Segment Restenosis at 13 Months Patient and Lesion Level Analysis* RR [95%CI] = 0.44 [0.33, 0.57] P< RR [95%CI] = 0.44 [0.33, 0.57] P< Major 2 endpoint * ITT: Includes all stent randomized lesions, whether or not a stent was implanted, and whether or not non study stents were placed ** Any lesion with restenosis per pt restenosis Stone GW. In press.

18 Multivariable Predictors of 1-Year 1 TLR (BMS Express patients, N=734) Variable HR (95% CI) P-value Total lesion length 1.03 [1.01, 1.05] Baseline RVD 0.22 [0.11, 0.42] < Insulin-treated diabetes 3.17 [1.23, 8.18] 0.02 Lesion ulceration 4.08 [1.53,10.88] Stone GW. ACC2009.

19 Multivariable Predictors of 1-Year 1 TLR (BMS Express patients, N=734) Variable Score HR (95% CI) P-value Total lesion length 40 mm [1.73,16.15] Baseline RVD 3.0 mm [1.63, 6.55] Insulin-treated diabetes [1.17, 7.66] 0.02 Lesion ulceration [1.30, 9.16] 0.01 Killip class [1.20, 5.20] 0.01 Stone GW. ACC2009.

20 1-Year TLR According to BMS Risk Score (N=2915) N=946 (32.5%) N=1520 (52.1%) N=449 (15.4%) Stone GW. ACC2009.

21 Multivariable Predictors of 13 Month In-segment Restenosis (BMS Express patients, N=290) Variable Score HR (95% CI) P-value Total lesion length 40 mm Total lesion length 30 - <40 mm [1.18,37.46] [1.10,10.51] 0.03 Baseline RVD 3.0 mm [2.18, 8.11] < Age 65.0 years [0.98, 3.24] 0.06 Stone GW. ACC2009.

22 13 Month In-segment Restenosis According to BMS Risk Score (N=1194) N=296 (24.8%) N=531 (44.7%) N=367 (30.7%) Stone GW. ACC2009.

23 Stent Selection in STEMI In pts with STEMI undergoing primary PCI, use of TAXUS rather than BMS results in: Comparable rates of stent thrombosis, reinfarction and death through 1 year Significant reductions in TLR, TVR and angiographic late loss and restenosis,, in all lesions except for those at low risk for restenosis Longer term follow-up is required to comprehensively assess the late safety and efficacy profile of DES in STEMI