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Effect of REG1 Anticoagulation System vs. Bivalirudin on Cardiovascular Outcomes Following PCI | Clinical Trial - REGULATE-PCI
Description:
The goal of the trial was to evaluate treatment with the novel anticoagulant (pegnivacogin) and reversal agent (anivamersen) compared with bivalirudin among patients undergoing percutaneous coronary intervention (PCI).
Pegnivacogin has affinity to factor IXa and has a half-life >24 hours. Anivamersen only has affinity to pegnivacogin. The combination of these two agents is termed the REG1 system.
Contribution to the Literature: The REGULATE-PCI trial showed that the REG1 anticoagulant system during PCI was associated with an unacceptably high rate of anaphylactic reactions.
Study Design
- Randomized
- Parallel
- Stratified
Patients undergoing PCI were randomized to the REG1 system (n = 1,616) (pegnivacogin [1 mg/kg] just prior to PCI, with reversal at the end of procedure by anivamersen [0.5 mg/kg]) versus bivalirudin (n = 1,616) (0.75 mg/kg bolus, then 1.75 mg/kg/hr for duration of procedure).
Prior to randomization, investigators had to specify access site (femoral/radial), vascular closure device (yes/no), planned target vessel, and ADP antagonist (clopidogrel/prasugrel/ticagrelor).
Patient population:
- Total number of enrollees: 3,232
- Duration of follow-up: 30 days
- Mean patient age: 65 years
- Percentage female: 25%
- Percentage diabetics: 35%
- Radial access: 50% of the REG1 group vs. 52% of the bivalirudin group
- Drug-eluting stents: 81% of the REG1 group vs. 52% of the bivalirudin group
- Vascular closure device: 32% of the REG1 group vs. 31% of the bivalirudin group
Inclusion criteria:
- Patients undergoing PCI stratified into three subgroups:
- Prior myocardial infarction (MI) within 7 days
- Prior MI >7 days, unstable angina, age >70 years, diabetes mellitus, chronic kidney disease, planned multivessel PCI, prior coronary artery bypass grafting (CABG), or peripheral vascular disease
- All other patients
Exclusion criteria:
- ST-elevation MI or use of lytics within previous 48 hours
- Glycoprotein IIb/IIIa inhibitors within 24 hours or planned during PCI
- Bivalirudin within 24 hours
- Planned staged PCI, CABG, or valve surgery within next 30 days
- Known allergy to study medication
Principal Findings:
The trial was terminated early (August 2014) due to an excess rate of serious allergic reactions with pegnivacogin. At the time of termination, 3,232 of planned 13,200 patients were enrolled.
The primary outcome of death, MI, stroke, or urgent target lesion revascularization at 3 days occurred in 6.7% of the REG1 group versus 6.4% of the bivalirudin group (p = 0.72).
Secondary outcomes:
- Bleeding at 3 days (BARC 3 or 5): 0.4% vs. 0.1% (p = 0.10), respectively, for REG1 vs. bivalirudin
- Stent thrombosis at 30 days: 0.1% vs. 0.8% (p < 0.01), respectively, for REG1 vs. bivalirudin
- Anaphylactic reaction at 3 days: 9 (1 fatal event) vs. 1 (no fatal events), respectively, for REG1 vs. bivalirudin
Interpretation:
Among patients undergoing PCI, the REG1 system was associated with an unacceptably high rate of anaphylactic reactions compared with bivalirudin. Since the trial was terminated early, any conclusions regarding efficacy and bleeding with the REG1 system are exploratory in nature.
References:
Lincoff AM, Mehran R, Povsic TJ, et al., on behalf of the REGULATE-PCI Investigators. Effect of REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial. Lancet 2015;Nov 4:[Epub ahead of print].
Presented by Dr. Roxana Mehran at ACC.15, San Diego, CA, March 15, 2015.
Keywords: ACC Annual Scientific Session, Adenosine Diphosphate, Anaphylaxis, Angiography, Anticoagulants, Aptamers, Nucleotide, Aspirin, Factor IXa, Fibrinolytic Agents, Hirudins, Longitudinal Studies, Oligonucleotides, Myocardial Infarction, Peptide Fragments, Percutaneous Coronary Intervention, Stroke, Recombinant Proteins
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