title: A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: results of the RADAR trial.
abstract: OBJECTIVE
  We sought to determine the degree of anticoagulation reversal required to mitigate bleeding, and assess the feasibility of using pegnivacogin to prevent ischaemic events in acute coronary syndrome (ACS) patients managed with an early invasive approach. REG1 consists of pegnivacogin, an RNA aptamer selective factor IXa inhibitor, and its complementary controlling agent, anivamersen. REG1 has not been studied in invasively managed patients with ACS nor has an optimal level of reversal allowing safe sheath removal been defined.
  
  
  RESULTS
  Non-ST-elevation ACS patients (n = 640) with planned early cardiac catheterization via femoral access were randomized 2:1:1:2:2 to pegnivacogin with 25, 50, 75, or 100% anivamersen reversal or heparin. The primary endpoint was total ACUITY bleeding through 30 days. Secondary endpoints included major bleeding and the composite of death, myocardial infarction, urgent target vessel revascularization, or recurrent ischaemia. Enrolment in the 25% reversal arm was suspended after 41 patients. Enrolment was stopped after three patients experienced allergic-like reactions. Bleeding occurred in 65, 34, 35, 30, and 31% of REG1 patients with 25, 50, 75, and 100% reversal and heparin. Major bleeding occurred in 20, 11, 8, 7, and 10% of patients. Ischaemic events occurred in 3.0 and 5.7% of REG1 and heparin patients, respectively.
  
  
  CONCLUSIONS
  At least 50% reversal is required to allow safe sheath removal after cardiac catheterization. REG1 appears a safe strategy to anticoagulate ACS patients managed invasively and warrants further investigation in adequately powered clinical trials of patients who require short-term high-intensity anticoagulation.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Povsic
authors.forename: John P
authors.initials: JP
authors.lastname: Vavalle
authors.forename: Laura H
authors.initials: LH
authors.lastname: Aberle
authors.forename: Jaroslaw D
authors.initials: JD
authors.lastname: Kasprzak
authors.forename: Mauricio G
authors.initials: MG
authors.lastname: Cohen
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Buller
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Jan H
authors.initials: JH
authors.lastname: Cornel
authors.forename: Andrzej
authors.initials: A
authors.lastname: Rynkiewicz
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ring
authors.forename: Uwe
authors.initials: U
authors.lastname: Zeymer
authors.forename: Madhu
authors.initials: M
authors.lastname: Natarajan
authors.forename: Nicolas
authors.initials: N
authors.lastname: Delarche
authors.forename: Steven L
authors.initials: SL
authors.lastname: Zelenkofske
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
mesh_terms: D054058:Acute Coronary Syndrome / Q000517:prevention & control*; D000925:Anticoagulants / Q000627:therapeutic use; D052157:Aptamers, Nucleotide / Q000627:therapeutic use*; D006328:Cardiac Catheterization / Q000379:methods; D003029:Coagulants / Q000627:therapeutic use*; D015949:Factor IXa / Q000037:antagonists & inhibitors; D005240:Feasibility Studies; D005260:Female; D006470:Hemorrhage / Q000517:prevention & control; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D009204:Myocardial Revascularization / Q000379:methods; D009841:Oligonucleotides / Q000627:therapeutic use; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D052157:Aptamers, Nucleotide; D003029:Coagulants; D009841:Oligonucleotides; C515724:RB 006; C515725:RB 007; D006493:Heparin; D015949:Factor IXa