title: Safety and efficacy of indigenously developed and manufactured bivalirudin in moderate/high-risk Indian patients undergoing percutaneous coronary intervention: the Bivaflo Registry.
abstract: BACKGROUND
  Current treatment strategies for percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS) include concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and antithrombotic therapy such as aspirin, clopidogrel, and unfractionated or low-molecular-weight heparin. The "direct thrombin inhibitor" bivalirudin has been associated with better efficacy and safety than heparin.
  
  
  OBJECTIVE
  The present study is performed to evaluate the safety and efficacy of an indigenously developed and manufactured bivalirudin (Bivaflo; Sun Pharmaceutical Industries Ltd., Mumbai) as the primary anticoagulation strategy during PCI in moderate-high risk patients with only provisional use of GPI.
  
  
  METHODS
  This prospective multicentered registry enrolled 439 patients in 11 tertiary care centers across India. Patients who had ACS or other clinical/angiographic characteristics, which increase risk during PCI, were enrolled in the registry. Bivaflo was administered as a bolus dose of 0.75 mg/kg, followed by infusion at a rate of 1.75 mg/kg/h during the procedure and optionally 0.25 mg/kg/h for 4 hours after the procedure at investigator's discretion. GPI use was discouraged except as bailout. The primary endpoints were composite and individual incidences of death, myocardial infarction (MI), urgent revascularization, subacute stent thrombosis (SAT), or bleeding at day 7/hospital discharge, whichever was earlier. The secondary endpoints were 30-day composite and individual incidences of death, MI, urgent revascularization, and SAT.
  
  
  RESULTS
  The mean age of the group was 58 +/- 10 years and 83% were males. Bivaflo was administered for a mean duration of 102 +/- 79 minutes, and 65% patients received Bivaflo infusion post-PCI. ACT values measured at 10 minutes after bolus and at the end of the PCI were found to be 339 +/- 110 and 336 +/- 104 seconds, respectively. GPI was provisionally used in only 4% (16) patients mostly due to new or suspected thrombus and obstructive dissection with decreased flow. At day 7/hospital discharge, there were no incidences of major adverse cardiac events or major bleeding. Minor bleeding occurred in only 4 patients (0.9%). The 30-day composite major adverse cardiac event rate was 0.68%. One death and two subacute thrombosis occurred during the 30-day follow-up.
  
  
  CONCLUSIONS
  Bivaflo is safe and effective sole anticoagulation strategy during PCI of moderate-high risk patients. Bivaflo administration was associated with no major bleeding events and extremely low in hospital and 30-day MACE rate. These rates were lower than expected MACE rates for such a subgroup of patients based on historical controls.
authors.affiliation: Escorts Heart Institute & Research Centre, New Delhi, India. ashok.seth@ehirc.com
authors.forename: Ashok
authors.initials: A
authors.lastname: Seth
authors.forename: Nakul
authors.initials: N
authors.lastname: Sinha
authors.forename: Keyur
authors.initials: K
authors.lastname: Parikh
authors.forename: Tejas
authors.initials: T
authors.lastname: Patel
authors.forename: M S
authors.initials: MS
authors.lastname: Hiremath
authors.forename: A B
authors.initials: AB
authors.lastname: Mehta
authors.forename: Praveen
authors.initials: P
authors.lastname: Chandra
authors.forename: Brian
authors.initials: B
authors.lastname: Pinto
authors.forename: K K
authors.initials: KK
authors.lastname: Sethi
authors.forename: Sengottuvelu
authors.initials: S
authors.lastname: Sengottuvelu
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000628:therapy; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012042:Registries; D018570:Risk Assessment
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; C074619:bivalirudin