Background In the HORIZONS-AMI(Harmonizing Outcomes with Revasculari Zati ON and Stents in Acute Myocardial Infarction) trial, 3,602 patients undergoing primary percutaneous coronary intervention(PCI) for ST-segment elevation myocardial infarction(STEMI) treated with bivalirudin had lower bleeding and mortality rates, but higher acute stent thrombosis rates compared with heparin + a glycoprotein Ⅱb / Ⅲa inhibitor(GPI). Subsequent changes in primary PCI, including the use of potent P2Y12 inhibitors, frequent radial intervention, and pre-hospital medication administration, were incorporated into the EUROMAX(European Ambulance Acute Coronary Syndrome Angiography) trial, which assigned 2,218 patients to bivalirudin versus heparin ± GPI before primary PCI.Objectives The goal of this study was to examine the outcomes of procedural anticoagulation with bivalirudin versus heparin ± GPI for primary PCI, given the evolution in primary PCI.Methods Databases from HORIZONS-AMI and EUROMAX were pooled for patient-level analysis. The Breslow-Day test evaluated heterogeneity between trials.Results A total of 5,800 patients were randomized to bivalirudin(n = 2,889) or heparin ± GPI(n = 2,911). The radial approach was used in 21.3% of patients, prasugrel / ticagrelor was used in 18.1% of patients, and GPI was used in 84.8% of the control group. Bivalirudin compared with heparin ± GPI resulted in reduced 30-day rates of major bleeding(4.2% vs. 7.8%; relative risk [RR]: 0.53; 95% confidence interval [CI]: 0.43 to0.66; P < 0.0001), thrombocytopenia(1.4% vs. 2.9%, RR: 0.48; 95% CI: 0.33 to 0.71; P = 0.0002), and cardiac mortality(2.0% vs. 2.9%; RR: 0.70; 95% CI: 0.50 to 0.97; P = 0.03), with nonsignificantly different rates of reinfarction, ischemia-driven revascularization, stroke, and all-cause mortality. Bivalirudin resulted in increased acute( < 24 h) stent thrombosis rates(1.2% vs. 0.2%; RR: 6.04; 95% CI: 2.55 to 14.31;P < 0.0001), with nonsignificantly different rates of subacute stent thrombosis. Composite net adverse clinical events were lower with bivalirudin(8.8% vs. 11.9%; RR: 0.74; 95% CI: 0.63 to 0.86; P < 0.0001). There was no significant heterogeneity between the 2 trials for these outcomes, and results were consistent across major subgroups.Conclusions Despite increased acute stent thrombosis, primary PCI with bivalirudin improved 30-day net clinical outcomes, with significant reductions in major bleeding, thrombocytopenia, and transfusions compared? with heparin ± GPI, results that were consistent with evolution in PCI technique and pharmacotherapy.(Harmonizing Outcomes with Revasculari Zati ON and Stents in Acute Myocardial Infarction [HORIZONS-AMI];NCT00433966)(European Ambulance Acute Coronary Syndrome Angiography [EUROMAX]; NCT01087723)(From: Journal of the American College of Cardiology Volume 65, Issue 1, 6-13 January 2015, Pages 27-38) Background In the HORIZONS-AMI (Harmonizing Outcomes with Revasculari Zati ON and Stents in Acute Myocardial Infarction) trial, 3,602 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) treated with bivalirudin had lower bleeding and mortality Rates, but higher acute stent thrombosis rates with heparin + a glycoprotein IIb / IIIa inhibitor (GPI). Subsequent changes in primary PCI, including the use of potent P2Y12 inhibitors, frequent radial intervention, and pre-hospital the EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial, which assigned 2,218 patients to bivalirudin versus heparin ± GPI before primary PCI. Objectives The goal of this study was to examine the outcomes of procedural anticoagulation with bivalirudin versus heparin ± GPI for primary PCI, given the evolution in primary PCI. Methods Databases from HORIZONS-AMI and EUROMAX wer The Breslow-Day test evaluated heterogeneity between trials. Results A total of 5,800 patients were randomized to bivalirudin (n = 2,889) or heparin ± GPI (n = 2,911). The radial approach was used in 21.3 % of patients, prasugrel / ticagrelor was used in 18.1% of patients, and GPI was used in 84.8% of the control group. Bivalirudin compared with heparin ± GPI resulted in reduced 30-day rates of major bleeding (4.2% vs. 7.8% ; relative risk [RR]: 0.53; 95% confidence interval [CI]: 0.43 to 0.66; P <0.0001), thrombocytopenia (1.4% vs. 2.9%, RR: 0.48; 95% CI: 0.33 to 0.71; 0.0002), and cardiac mortality (2.0% vs. 2.9%; RR: 0.70; 95% CI: 0.50 to 0.97; P = 0.03) with nonsignificantly different rates of reinfarction, ischemia- driven revascularization, stroke, and all-cause mortality . Bivalirudin resulted in increased acute (<24 h) stent thrombosis rates (1.2% vs. 0.2%; RR: 6.04; 95% CI: 2.55 to 14.31; P <0.0001) with nonsignificantly different rates of su bacute sComposite net adverse clinical events were lower with bivalirudin (8.8% vs. 11.9%; RR: 0.74; 95% CI: 0.63 to 0.86; P <0.0001) There was no significant heterogeneity between the 2 trials for these outcomes, and results were consistent across major subgroups.Conclusions Despite increased acute stent thrombosis, primary PCI with bivalirudin improved 30-day net clinical outcomes, with significant reductions in major bleeding, thrombocytopenia, and transfusions compared? with heparin ± GPI, results that were consistent with (Harmonizing Outcomes with Revasculari Zati ON and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966) (European Ambulance Acute Coronary Syndrome Angiography [EUROMAX]; NCT01087723) (From: Journal of the American College of Pharmacology Cardiology Volume 65, Issue 1, 6-13 January 2015, Pages 27-38)