Tirofiban is way superior to cangrelor at reaching immediate and potent inhibition of platelet aggregation in patients present process major percutaneous coronary intervention for ST-elevation MI.
And cangrelor, in flip, is superior to oral prasugrel, per the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual assembly of the European Association of Percutaneous Cardiovascular Interventions.
Moreover, contrary to archaic wisdom, chewed prasugrel (Effient) proved no higher than swallowing the tablets total for platelet inhibition, mentioned Dr. Valgimigli, an interventional coronary heart specialist at the University of Bern (Switzerland).
He explained that peculiar administration of the more contemporary oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients present process percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) would no longer present optimum early inhibition of platelet aggregation. The parenteral antiplatelet remedy tirofiban and cangrelor were shown to compose sooner and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.
But there became no head-to-head comparative recordsdata for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the surroundings of major PCI for STEMI. This became the impetus for FABOLUS FASTER, the first search for to examine the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral remedy, in comparison with chewed prasugrel, one more beforehand unexamined but highly shiny inconvenience.
The three-center, multinational, open-price FABOLUS FASTER trial randomized 122 patients present process major PCI for STEMI to 1 of three arms: a archaic intravenous bolus and a pair of-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm by which patients didn’t receive either drug nonetheless were as an alternative randomized to a 60-mg loading dose of chewed or total prasugrel tablets.
The important thing search for endpoint became inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry per 20 mcmol/L of adenosine diphosphate (ADP).
Tirofiban became the unequivocal winner with 95% inhibition, as in comparison with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed total, although the focus of prasugrel’s stuffed with life metabolite became a ways better at 62.3 ng/mL after prasugrel became chewed, in comparison with 17.1 ng/mL when swallowed in integral tablet invent.
The rate of nonresponsiveness to tirofiban as outlined by better than 59% platelet aggregation became zero for tirofiban for the length of its 2-hour infusion, then a scant 8% thereafter for the length of repeated checking out at 3 and 4-6 hours. In distinction, the cangrelor nonresponsiveness rate became 50%-58% for the length of the 2-hour infusion, rising to 82% at 3 hours.
FABOLUS FASTER, whereas no longer powered for scientific endpoints, may perhaps well furthermore on the opposite hand bear crucial scientific implications, per Dr. Valgimigli. First, the prevalence of the intravenous remedy tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet remedy over oral therapy for the length of the acute section of STEMI therapy.
Moreover, tirofiban’s prominent efficiency — and the excessive residual platelet reactivity linked to cangrelor — makes a mighty case for immense comparative, randomized trials of the two remedy, with laborious scientific endpoints.
Discussant Christoph K. Naber, MD, PhD, opined that he personally would no longer bear in tips the FABOLUS FASTER results be aware changing, for a pair of causes.
“Platelet inhibition measured by ADP in vitro is no longer essentially linked to ideal effects in vivo. We all know that platelets are activated by multiple mechanisms, and the ADP pathway is true one of them,” mentioned Dr. Naber, an interventional coronary heart specialist at the Wilhemshaven (Germany) Sanatorium.
Moreover, there’s a decent reason no glycoprotein IIb/IIIA inhibitors are popular for remedy of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout conditions, equivalent to complicated lesions with immense thrombus burden. It be because tirofiban’s potent antiplatelet activity is accompanied by a excessive chance of bleeding, he added.
Nonetheless, Dr. Valgimigli smartly-known that this conviction about impolite bleeding chance is largely per older experiences by which glycoprotein IIb/IIIA inhibitors were administered for prolonged length by femoral score admission to sites. He argued that it is time for immense scientific trials inspecting the chance/profit ratio of short infusion of these agents in the contemporary be aware of major PCI for STEMI.
Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were printed online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).
Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, equipped an institutional be taught grant to habits the quest for. He also disclosed receiving be taught grants and private expenses outdoors the scope of this search for from a dozen pharmaceutical and medical tool firms. Dr. Naber reported having no financial conflicts.
This article first and major regarded on MDedge.com.
