title: Safety and Efficacy of Bivalirudin in Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention: From the REPLACE-2, ACUITY and HORIZONS-AMI Trials.
abstract: Optimal antithrombotic pharmacotherapy in patients affected by diabetes mellitus (DM) undergoing percutaneous coronary intervention is unclear. We sought to evaluate the safety and efficacy of bivalirudin compared with heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) in patients with DM undergoing percutaneous coronary intervention. We pooled patient-level data from the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events-2, Acute Catheterization and Urgent Intervention Triage strategy, and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trials. The primary efficacy end point was the incidence of major adverse cardiac events, defined as the composite of death, myocardial infarction, or unplanned revascularization at 30 days. The primary safety end point was the incidence of 30-day non-coronary artery bypass graft-related major bleeding. All-cause mortality was reported at 30 days and 1 year. Of the 14,737 patients included in the pooled database, 3,641 (24.7%) had DM. Patients with DM had higher rates of 30-day major bleeding and 30-day and 1-year all-cause mortality. There were no differences in 30-day major adverse cardiac events between bivalirudin versus heparin plus GPI in patients with DM (6.9% vs 7.8%; relative risk [RR] 0.89, 95% CI 0.71 to 1.12) or without DM (7.5% vs 6.7%; RR 1.11, 95% CI 0.97 to 1.27; pinteraction = 0.10). Bivalirudin treatment was associated with reduced risk of major bleeding in similar magnitude in patients with DM (4.3% vs 6.6% RR 0.68, 95% CI 0.51 to 0.89) or without DM (3.2% vs 6.1%; RR 0.51, 95% CI 0.43 to 0.61; pinteraction = 0.15). The hemorrhagic benefit of bivalirudin was noted for both access site- and non-access site-related bleeding. Overall, bivalirudin treatment was associated with a significant 1-year mortality benefit (2.7% vs 3.3%; RR 0.82, 95% CI 0.68 to 0.98; p = 0.03), which was consistent between patients with or without DM (pinteraction = 0.30). In conclusion, compared with heparin plus GPI, bivalirudin was associated with similar 30-day antithrombotic efficacy and better 30-day freedom from bleeding and 1-year mortality, irrespective of diabetic status.
authors.affiliation: Interventional Cardiovascular Research and Clinical Trials, The Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Giustino
authors.affiliation: Interventional Cardiovascular Research and Clinical Trials, The Icahn School of Medicine at Mount Sinai, New York, New York; Clinical Trials Center, Cardiovascular Research Foundation, New York, New York. Electronic address: Roxana.Mehran@mountsinai.org.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Interventional Cardiovascular Research and Clinical Trials, The Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Sameer
authors.initials: S
authors.lastname: Bansilal
authors.affiliation: Department of Cardiology, New York University Medical Center, New York, New York.
authors.forename: Frederick
authors.initials: F
authors.lastname: Feit
authors.affiliation: Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio.
authors.forename: Michael
authors.initials: M
authors.lastname: Lincoff
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Efthymios N
authors.initials: EN
authors.lastname: Deliargyris
authors.affiliation: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York; Division of Cardiology, NewYork-Presbyterian Hospital, Columbia University Medical Center, New York, New York.
authors.forename: Ajay J
authors.initials: AJ
authors.lastname: Kirtane
authors.affiliation: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York; Division of Cardiology, NewYork-Presbyterian Hospital, Columbia University Medical Center, New York, New York; Department of Cardiology, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Généreux
authors.affiliation: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Redfors
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Jayne
authors.initials: J
authors.lastname: Prats
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Debra
authors.initials: D
authors.lastname: Bernstein
authors.affiliation: Department of Medicine, New York Methodist Hospital, Brooklyn, New York.
authors.forename: Sorin J
authors.initials: SJ
authors.lastname: Brener
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Simona
authors.initials: S
authors.lastname: Skerjanec
authors.affiliation: Division of Cardiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Lansky
authors.affiliation: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York.
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Francese
authors.affiliation: Interventional Cardiovascular Research and Clinical Trials, The Icahn School of Medicine at Mount Sinai, New York, New York; Clinical Trials Center, Cardiovascular Research Foundation, New York, New York.
authors.forename: George D
authors.initials: GD
authors.lastname: Dangas
authors.affiliation: Clinical Trials Center, Cardiovascular Research Foundation, New York, New York; Division of Cardiology, NewYork-Presbyterian Hospital, Columbia University Medical Center, New York, New York.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D000368:Aged; D000991:Antithrombins / Q000627:therapeutic use*; D016022:Case-Control Studies; D048909:Diabetes Complications / Q000150:complications* / Q000401:mortality; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D006629:Hirudins; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D010446:Peptide Fragments / Q000627:therapeutic use*; D062645:Percutaneous Coronary Intervention; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; C074619:bivalirudin