Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction: Primary Results of the FABOLUS-FASTER Trial

• Published in: Circulation (New York, N.Y.) N.Y.), 2020-08, Vol.142 (5), p.441-454
• Main Authors: Gargiulo, Giuseppe, Esposito, Giovanni, Avvedimento, Marisa, Nagler, Michael, Minuz, Pietro, Campo, Gianluca, Gragnano, Felice, Manavifar, Negar, Piccolo, Raffaele, Tebaldi, Matteo, Cirillo, Plinio, Hunziker, Lukas, Vranckx, Pascal, Leonardi, Sergio, Heg, Dik, Windecker, Stephan, Valgimigli, Marco
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - pharmacology; Adenosine Monophosphate - administration & dosage; Adenosine Monophosphate - analogs & derivatives; Adenosine Monophosphate - blood; Adenosine Monophosphate - pharmacology; Adenosine Monophosphate - therapeutic use; Administration, Oral; Aged; Aged, 80 and over; Area Under Curve; Aspirin - therapeutic use; Cardiac Catheterization; Comorbidity; Female; Heart - physiopathology; Humans; Infusions, Intravenous; Male; Mastication; Middle Aged; Original s; Percutaneous Coronary Intervention; Platelet Aggregation - drug effects; Polypharmacy; Prasugrel Hydrochloride - administration & dosage; Prasugrel Hydrochloride - blood; Prasugrel Hydrochloride - pharmacology; Prasugrel Hydrochloride - therapeutic use; Proportional Hazards Models; Purinergic P2Y Receptor Antagonists - administration & dosage; Purinergic P2Y Receptor Antagonists - blood; Purinergic P2Y Receptor Antagonists - pharmacology; Purinergic P2Y Receptor Antagonists - therapeutic use; ST Elevation Myocardial Infarction - drug therapy; ST Elevation Myocardial Infarction - therapy; Tablets; Tirofiban - administration & dosage; Tirofiban - blood; Tirofiban - pharmacology; Tirofiban - therapeutic use; Treatment Outcome
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.120.046928

BACKGROUND:Standard administration of newer oral P2Y12 inhibitors, including prasugrel or ticagrelor, provides suboptimal early inhibition of platelet aggregation (IPA) in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention. We aimed to investigate the effects of cangrelor, tirofiban, and prasugrel, administered as chewed or integral loading dose, on IPA in patients undergoing primary percutaneous coronary intervention. METHODS:The FABOLUS-FASTER trial (Facilitation Through Aggrastat or Cangrelor Bolus and Infusion Over PrasugrelA Multicenter Randomized Open-Label Trial in Patients with ST-Elevation Myocardial Infarction Referred for Primary Percutaneous Intervention) is an investigator-initiated, multicenter, open-label, randomized study. A total of 122 P2Y12-naive patients with ST-segment–elevation myocardial infarction were randomly allocated (1:1:1) to cangrelor (n=40), tirofiban (n=40) (both administered as bolus and 2-hour infusion followed by 60 mg of prasugrel), or 60-mg loading dose of prasugrel (n=42). The latter group underwent an immediate 1:1 subrandomization to chewed (n=21) or integral (n=21) tablets administration. The trial was powered to test 3 hypotheses (noninferiority of cangrelor compared with tirofiban using a noninferiority margin of 9%, superiority of both tirofiban and cangrelor compared with chewed prasugrel, and superiority of chewed prasugrel as compared with integral prasugrel, each with α=0.016 for the primary end point, which was 30-minute IPA at light transmittance aggregometry in response to 20 μmol/L adenosine diphosphate. RESULTS:At 30 minutes, cangrelor did not satisfy noninferiority compared with tirofiban, which yielded superior IPA over cangrelor (95.0±8.9 versus 34.1±22.5; P