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HORIZONS –AMI A Prospective, Multicenter Randomized Trial of Heparin Plus GPIIb/IIIa Inhibitors vs. Bivalirudiin STEMI: Final 3-year results from the HORIZONS-

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Presentation on theme: "HORIZONS –AMI A Prospective, Multicenter Randomized Trial of Heparin Plus GPIIb/IIIa Inhibitors vs. Bivalirudiin STEMI: Final 3-year results from the HORIZONS-"— Presentation transcript:

1 HORIZONS –AMI A Prospective, Multicenter Randomized Trial of Heparin Plus GPIIb/IIIa Inhibitors vs. Bivalirudiin STEMI: Final 3-year results from the HORIZONS- AMI Trial Stone GW et al. Lancet 2011: Published online June 13, DOI: /S (11)

2 Background ● At 1-year in the 2x2 factorial prospective, randomized HORIZONS-AMI trial: –Bivalirudin alone compared to heparin plus GPIIb/IIIa inhibitors resulted in comparable rates of MI and stent thrombosis, with significantly reduced rates of major bleeding and mortality (all- cause and cardiac) ● 3-year results are assessed in this report –Prespecified endpoints in the pharmacology arm at 3 years included death, reinfarction, ischemia driven target lesion revascularization, stroke, and the composite of these (MACE); non-CABG major bleeding and the composite of all net adverse clinical events (NACE). Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)

3 Harmonizing Outcomes with Revascularization and Stents in AMI 3602 pts with STEMI with symptom onset ≤12 hours Emergent angiography, followed by triage to… Primary PCI CABG – Medical Rx – UFH + GP IIb/IIIa inhibitor (abciximab or eptifibatide) Bivalirudin monotherapy (± provisional GP IIb/IIIa) Aspirin, thienopyridine R 1: pts eligible for stent randomization R 3:1 Bare metal EXPRESS stent Paclitaxel-eluting TAXUS stent Clinical FU at 30 days, 6 months, 1 year, and then yearly through 3 years; angio FU at 13 months Clinical FU at 30 days, 6 months, 1 year, and then yearly through 3 years; angio FU at 13 months Stone, GW N Engl J Med 2008;358:

4 Harmonizing Outcomes with Revascularization and Stents in AMI R 1:1 Randomized * Biomarkers WNL and no DS >50% by core lab determination (30 day FU only) 1-Year FU Eligible 3-Year FU Withdrew Withdrew Lost to FU Lost to FU pts with STEMI Not true MI* Not true MI* Year FU UFH + GP IIb/IIIa N=1802 Bivalirudin N=1800 N=1628 N=1634 N=1774N=1771 N=1702 N=1696 Withdrew Withdrew Lost to FU Lost to FU Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)

5 Antiplatelet agent use (%) Regular* aspirin use (%)Regular* thieno. use (%) *Taken >50% of days since last visit 98% 97% 96% 94% 93.% 93% 88% 87% 68% 66% All P = NS Pharmacology Randomization: Aspirin and Thienopyridine Use 33% 36% 95% Bivalirudin alone (n=1800)Heparin + GPIIb/IIIa(n=1802) 94% 95% 26% 27% Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)

6 * 3-Year Major Bleeding (non-CABG)* * Intracranial, intraocular, retroperitoneal, access site bleed requiring intervention/surgery, hematoma ≥5 cm, hgb ↓ ≥3g/dL with or ≥4g/dL w/o overt source; reoperation for bleeding; or blood product transfusion (0.51, 0.80) P= yr HR (95%CI) 6.9% 6.9% 10.5% Major Bleeding (%) Months 369 Bivalirudin alone (n=1800) Heparin + GPIIb/IIIa (n=1802) 9.4% 6.0% Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)

7 3-Year Cardiac Mortality ' % 5.1% Time in Months Bivalirudin alone (n=1800)Heparin + GPIIb/IIIa (n=1802) Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)

8 3-Year Cardiac Mortality Landmark analysis Heparin + GP IIb/IIIa (n=1802) Bivalirudin (n=1800) 3 year HR (95% CI) –0.86 p= day HR (95% CI) 0.62 (0.40 – 0.96) p= % 1.1% Cardiac mortality (%) 1.8% 2.9% Months Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)

9 3-Year Reinfarction Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)

10 3-Year Reinfarction Landmark analysis year HR (95% CI) 0.66 (0.49 – 0.90) p= day HR (95% CI) 1.07 (0.66 – 1.73) p= % 4.4% Reinfarction (%) 1.8% 1.9% Months Heparin + GPIIb/IIIa (n=1802) Bivalirudin (n=1800) Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)

11 3-Year All-Cause Mortality or Reinfarction Landmark analysis Heparin + GPIIb/IIIa (n=1802) Bivalirudin (n=1800) 3-year HR (95% CI) 0.72 (0.58 – 0.91) p= day HR (95% CI) 0.84 (0.61 – 1.16) p= % 7.8% All-cause mortality or reinfarction (%) 3.8% 4.5% Months Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)

12 3-year MACE Components* UFH + GPI (N=1802) Bivalirudin (N=1800) HR [95%CI]P Value Number needed to treat Death7.7%5.9%0.75 (0.58,0.97) Cardiac - Cardiac5.1%2.9%0.56 (0.40,0.80) Non cardiac - Non cardiac2.8%3.1%0.62 Reinfarction8.2%6.2%0.76 (0.59,0.92) Q-wave - Q-wave3.8%3.4% Non Q-wave - Non Q-wave4.9%3.2% Death or reinfarction14.5%11.3%0.72 (0.58,0.91) Ischemic TVR12.1%14.2%0.06 Stroke2.0%1.7%0.50 *Kaplan-Meier estimates, CEC adjudicated Stone, GW Lancet 2011 Published online June 13. DOI: /S (11) MACE= death, reinfarction, ischemia-driven target vessel revascularization, stroke

13 3-year Bleeding Endpoints UFH + GPI (N=1802) Bivalirudin (N=1800) HR (95% CI)P Value Number needed to treat Major bleeding, non- CABG10.5%6.9%0.64 ( ) Major bleeding, including CABG12.8%8.9%< Blood transfusion5.1%3.5% TIMI Major or Minor10.9%7.0%< TIMI Major6.1%4.1% TIMI Minor5.0%3.2% GUSTO (any)12.7%8.8% GUSTO severe/life- threatening0.9%1.0%0.74 GUSTO moderate6.3%4.7% GUSTO mild6.2%4.0%0.003 Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)

14 3-Year Stent Thrombosis (ARC Definite/Probable) Stone, GW Lancet 2011 Published online June 13. DOI: /S (11) ARC= Academic Research Consortium

15 3-Year Stent Thrombosis* (N=3202) UFH + GPI (N=1591) Bivalirudin (N=1611) P Value ARC definite 4.1%4.2%0.87 ARC probable 1.0%0.3%0.02 ARC definite or probable 5.1%4.5%0.49 Early <30 days 2.1%2.6%0.31 Late (30 days to 1 year) 1.0%0.9%0.64 Very late (> 1 year) 2.2%1.1%0.02 <24 hours 0.3%1.5% hours to 3 years 4.8%3.1%0.01 *All Kaplan-Meier estimates; all CEC adjudicated Stone, GW Lancet 2011 Published online June 13. DOI: /S (11) ARC= Academic Research Consortium

16 Limitations ● Open label design, but high compliance to study processes ● Study applicable to patients enrolled, although there were few exclusions ● Slight imbalances between baseline groups and outpatient thienopyridine use, but none of the results were altered in multivariable adjustment ● Results were not adjusted for multiple comparisons and should be regarded as hypothesis-generating ● 8.0% of patients in the pharmacology randomization were not available for 3-year follow-up ● The impact of a comparison with heparin alone, or with higher use of radial access are not known Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)

17 Conclusions: Pharmacology Randomization ● In this large-scale, prospective, randomized trial of pts with STEMI undergoing primary PCI, the initial treatment with bivalirudin alone compared to heparin plus GPIIb/IIIa inhibitors at 3 years resulted in: –A significant 36% reduction in major bleeding and a significant 24% reduction in reinfarction, with non significantly different rates of stent thrombosis, TVR and stroke –A significant 44% reduction in cardiac mortality and a 25% reduction in all-cause mortality, the latter representing 18 lives saved per 1000 patients treated with bivalirudin (NNT = 54 to save 1 life) Stone, GW Lancet 2011 Published online June 13. DOI: /S (11)


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