1 / 22

Background

Bivalirudin Reduces Cardiac Mortality in Patients with and Without Major Bleeding The HORIZONS-AMI Trial. Gregg W. Stone, Tim Clayton, Roxana Mehran, Efthymios N. Deliargyris, Jayne Prats, Stuart J. Pocock.

rigg
Download Presentation

Background

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Bivalirudin Reduces Cardiac Mortality in Patients with and Without Major Bleeding The HORIZONS-AMI Trial Gregg W. Stone, Tim Clayton, Roxana Mehran, Efthymios N. Deliargyris, Jayne Prats, Stuart J. Pocock

  2. In the HORIZONS-AMI trial, treatment with bivalirudin compared to heparin + a GPIIb/IIIa inhibitor in pts with STEMI undergoing primary PCI resulted in markedly reduced rates of cardiac mortality, which is usually attributed to decreased bleeding Whether the reduction in mortality with bivalirudin can be fully ascribed to reduced bleeding is unknown Background

  3. HORIZONS-AMI: 3-Year Cardiac Mortality Bivalirudin alone (n=1800) 6 Heparin + GPIIb/IIIa (n=1802) 5.1% 3-yr HR [95%CI]= 5 0.56 [0.40, 0.80] P=0.001 4 Cardiac Mortality (%) 3 2.9% 2 Δ=38 cardiac deaths 1 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Months Number at risk 1800 1689 1660 1633 1611 1574 1098 Bivalirudin alone 1802 1670 1643 1593 1568 1525 1043 Heparin+GPIIb/IIIa * 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 Stone GW et al. Lancet 2011;377:2193-204

  4. HORIZONS-AMI: Multivariable Model for 3-Year Cardiac Mortality (all pts) Other variables in model: current smoker, female gender, prior MI, # vessels treated, hemoglobin

  5. HORIZONS-AMI: 3-Year Major Bleeding* Bivalirudin alone (n=1800) 12 Heparin + GPIIb/IIIa (n=1802) 10.5% 10 8 6.9% Major Bleeding, non-CABG (%) 6 3-yr HR [95%CI]= 4 Δ=64 major bleeds 0.64 [0.51, 0.80] P<0.001 2 0 0 3 6 9 12 15 18 21 24 27 30 33 36 Months Number at risk 1800 1601 1572 1544 1523 1485 1039 Bivalirudin alone 1802 1534 1509 1465 1442 1402 957 Heparin+GPIIb/IIIa * 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 Stone GW et al. Lancet 2011;377:2193-204

  6. HORIZONS-AMI: Impact of Major Bleeding 12% No major bleed (n=3296) Major bleed (n=306) 11.6% 10% 8% HR [95%CI] = 5.81 [3.92, 8.62] P<0.001 6% Cardiac mortality (%) 4% 3.3% 2% 0% 0 1 2 3 Years No bleed 3296 3043 2944 1996 Bleed 306 255 232 145

  7. HORIZONS-AMI: 3-year Cardiac Mortality in Pts with vs without Major Bleeding HR [95%CI] = 5.67 [3.59, 8.96] P<0.0001 Pint = 0.34 HR [95%CI] = 4.62 [2.04, 10.45] P=0.002 27/185 61/1617 7/121 43/1679 % major bleed in pts with cardiac death 30.7% (27/88) 14.0% (7/50) P=0.03

  8. HORIZONS-AMI: 3-Year Cardiac Mortality in pts with and without Major Bleeding According to Treatment Pint = 0.34 HR [95%CI] = 2.56 [1.12, 5.88] P=0.02 HR [95%CI] = 1.47 [1.00, 2.17] P=0.048 27/185 7/121 61/1617 43/1679 # fewer cardiac deaths with bivalirudin ∆ = 20 deaths ∆ = 18 deaths

  9. HORIZONS-AMI: Mortality in Patients with Major Bleeding 16% 14.6% 14% 12% HR [95%CI] = 0.39 (0.17 - 0.89) P=0.025 Heparin + GPI (n=185) 10% Bivalirudin (n=121) Cardiac mortality* (%) 8% 5.8% 6% 4% 2% 0% 0 1 2 3 Years UFH + GPI 185 151 138 86 Bivalirudin 121 104 94 59 *From the time of a major bleed

  10. HORIZONS-AMI: Multivariable Model for 3-Year Cardiac Mortality in Pts With Major Bleeding Other variables in model: diabetes, Killip class, LAD treated, hemoglobin, creatinine

  11. HORIZONS-AMI: Frequency and Severity of Major Bleeding *In pts with that type of major bleed

  12. HORIZONS-AMI: Hemoglobin Levels in Pts with Major Bleeding P=0.03 P=0.08 ± 1.9 ± 2.3 ± 1.9 ± 2.0 P=0.31 ± 1.7 ± 2.0

  13. HORIZONS-AMI: RBCTransfusions Median # units (among pts transfused) UFH + GPI: 2 [2, 5] Bivalirudin: 3 [2, 5] P=0.10 Number of pts Number of RBC units transfused

  14. HORIZONS-AMI: Mortality in Pts without Major Bleeding* 5% 4% 3.8% Heparin + GPI (n=1802) 3% Bivalirudin (n=1800) 2.6% Cardiac mortality (%) 2% HR [95%CI] = 0.67 (0.46 to 1.00) P=0.046 1% 0% 0 1 2 3 Years UFH+GPI 1802 1506 1441 957 Bivalirudin 1800 1569 1521 1039 *KM curve with censoring at time of major bleed

  15. HORIZONS-AMI: Multivariable Model for 3-Year Cardiac Mortality in Pts Without Major Bleeding* Other variables in model: current smoker, female gender, prior MI, # vessels treated *Pts censored at time of bleed

  16. HORIZONS-AMI: Incidence and Impact of In-hospital Acquired Thrombocytopenia* Acquired thrombocytopenia (n=404) No thrombocytopenia (n=3053) 10% 8.1% 8% P=0.004 6% HR [95%CI] = 2.76 [1.85, 4.14] P<0.001 13.2% Cardiac mortality (%) 4% 3.1% 10.1% 2% 0% 0 1 2 3 Years No thromb 3053 2832 2726 1833 Thrombocytopenia Thromb 404 341 330 217 * Nadir platelet count <150,000 in pts w/o baseline thrombocytopenia

  17. HORIZONS-AMI: 3-year Cardiac Mortality in Pts with vs without In-hospital Acquired Thrombocytopenia HR [95%CI] = 4.36 [2.73, 6.95] P<0.0001 Pint = 0.006 HR [95%CI] = 1.44 [0.50, 4.12] P=0.51 28/228 52/1493 4/176 39/1560 % thrombocytopenia in pts with cardiac death 35.0% (28/80) 9.3% (4/43) P=0.002

  18. HORIZONS-AMI: 3-year Cardiac Mortality in Pts with vs without Acquired Thrombocytopenia* According to Treatment Pint = 0.006 HR (95%CI) = 5.56 (2.00, 16.67) P=0.0001 HR (95%CI) = 1.41 (0.47 to 1.09) P=0.12 28/228 4/176 52/1493 39/1560 Nadir platelet count <150,000 in pts w/o baseline thrombocytopenia

  19. HORIZONS-AMI: Interaction Between Major Bleeding and Acquired Thrombocytopenia* Ptrend <0.0001 P=0.005 P=0.03 14/81 17/205 18/323 74/2848 % of 123 cardiac deaths 11.4% (n=14) 13.8% (n=17) 14.6% (n=18) 60.2% (n=74) *Excluding pts with baseline thrombocytopenia

  20. HORIZONS-AMI: Interaction Between Major Bleeding, Thrombocytopenia* and Treatment Ptrend<0.0001 Ptrend= 0.17 13/50 1/31 12/125 5/80 15/178 3/145 34/1480 40/1368 *Excluding pts with baseline thrombocytopenia

  21. HORIZONS-AMI: Multivariable Model for 3-Year Cardiac Mortality, Including Adverse Events Excludes 145 pts with thrombocytopenia at baseline. Other variables in model: current smoker, female gender, prior MI, # vessels treated, hemoglobin

  22. Conclusions • In HORIZONS-AMI, treatment with bivalirudin rather than UFH + GPI resulted in a marked reduction in cardiac mortality in pts with STEMI undergoing primary PCI • ~Half of the reduction in cardiac deaths with bivalirudin occurred in pts without major bleeding • In addition to reducing major bleeding, bivalirudin reduced the occurrence of thrombocytopenia, which contributed to the improved survival in pts with and without major bleeding • The adverse effects of major bleeding and thrombocytopenia are mitigated in pts treated with bivalirudin rather than UFH + GPI, and bivalirudin was strongly associated with reduced cardiac mortality even after accounting for bleeding and thrombocytopenia – further studies are required to identify the non-hematologic benefits of bivalirudin

More Related