Gregg W Stone1, Roxana Mehran2, Patrick Goldstein3, Bernhard Witzenbichler4, Arnoud Van't Hof5, Giulio Guagliumi6, Christian W Hamm7, Philippe Généreux8, Peter Clemmensen9, Stuart J Pocock10, Bernard J Gersh11, Debra Bernstein12, Efthymios N Deliargyris12, Philippe Gabriel Steg13. 1. Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, New York. Electronic address: gs2184@columbia.edu. 2. Mount Sinai Medical Center and the Cardiovascular Research Foundation, New York, New York. 3. Lille University Hospital, Lille, France. 4. Helios Amperkliniken AG, Munich, Germany. 5. Isala Klinieken, Zwolle, the Netherlands. 6. Ospedale Papa Giovanni XXIII, Bergamo, Italy. 7. Kerckhoff Clinic and Thoraxcenter, Bad Nauheim, Germany. 8. Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada; Cardiovascular Research Foundation, New York, New York. 9. Rigshospitalet, Copenhagen, Denmark. 10. London School of Hygiene and Tropical Medicine, London, United Kingdom. 11. Mayo Clinic College of Medicine, Rochester, Minnesota. 12. The Medicines Company, Parsippany, New Jersey. 13. DHU FIRE, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France; Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France; NHLI, Imperial College, Royal Brompton Hospital, London, United Kingdom.
Abstract
BACKGROUND: In the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial, 3,602 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) treated withbivalirudin 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 tobivalirudin 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 to 0.66; 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 RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966) (European Ambulance Acute Coronary Syndrome Angiography [EUROMAX]; NCT01087723).
RCT Entities:
BACKGROUND: In the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON 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 to 0.66; 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 RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966) (European Ambulance Acute Coronary Syndrome Angiography [EUROMAX]; NCT01087723).
Authors: Hector Tamez; Duane S Pinto; Ajay J Kirtane; Claire Litherland; Robert W Yeh; George D Dangas; Roxana Mehran; Efthymios N Deliargyris; Guillermo Ortiz; C Michael Gibson; Gregg W Stone Journal: JAMA Cardiol Date: 2017-06-01 Impact factor: 14.676
Authors: Suzanne V Arnold; Shu-Xia Li; Karen P Alexander; John A Spertus; Brahmajee K Nallamothu; Jeptha P Curtis; Mikhail Kosiborod; Aakriti Gupta; Tracy Y Wang; Haiqun Lin; Kumar Dharmarajan; Kelly M Strait; Timothy J Lowe; Harlan M Krumholz Journal: J Am Heart Assoc Date: 2015-06-15 Impact factor: 5.501
Authors: Abdul Hafeez Ahmad Hamdi; Ahmad Fauzi Dali; Thimarul Huda Mat Nuri; Muhammad Syafiq Saleh; Noor Nabila Ajmi; Chin Fen Neoh; Long Chiau Ming; Amir Heberd Abdullah; Tahir Mehmood Khan Journal: Front Pharmacol Date: 2017-07-11 Impact factor: 5.810
Authors: Leonardo De Luca; Furio Colivicchi; Michele Massimo Gulizia; Francesco Rocco Pugliese; Maria Pia Ruggieri; Giuseppe Musumeci; Gian Alfonso Cibinel; Francesco Romeo Journal: Eur Heart J Suppl Date: 2017-05-02 Impact factor: 1.803