Chewed prasugrel proved no more effective at inhibiting platelets than whole-swallowed prasugrel; prasugrel in either form was inferior to both tirofiban and cangrelor.
Tirofiban showed the best inhibition of platelet aggregation (IPA), outperforming both cangrelor and prasugrel in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), according to results of the FABOLUS-FASTER randomized controlled trial presented Saturday at the PCR e-Course.
Marco Valgimigli, MD, PhD, of Bern University Hospital, Switzerland, presented the results at PCR. Giuseppe Gargiulo, MD, PhD, of Bern University Hospital and Federico II University of Naples, Italy, and colleagues reported their findings in a manuscript simultaneously published online in Circulation.
Standard administration of newer oral P2Y12 inhibitors provide suboptimal early IPA in STEMI patients undergoing primary PCI. The investigators sought to evaluate the effects of cangrelor, tirofiban and prasugrel (which was chewed or swallowed whole) of IPA in these patients.
FABOLUS-FASTER is an investigator-initiated, multicenter, open-label, randomized study. A total of 122 STEMI patients were randomized assigned (1:1:1) to receive cangrelor (n=40), tirofiban (n=40) or prasugrel (n=42). The prasugrel patients were further randomized to chew (n=21) or swallow the tablets whole (n=21). The trial was powered to test whether cangrelor was noninferior to tirofiban, whether tirofiban and cangrelor were superior to chewed prasugrel, and whether chewed prasugrel was superior to prasugrel that was swallowed whole.
At 30 minutes, cangrelor fell short of noninferiority to tirofiban. Instead, tirofiban showed superior IPA to cangrelor (95.0 ± 8.9 vs. 34.1 ± 22.5; p<0.001). Cangrelor and tirofiban did both show superiority over chewed prasugrel (IPA: 10.5 ± 11.0; p<0.001 for both comparisons). Chewed prasugrel did not show a difference from whole-swallowed prasugrel (IPA: 6.3±11.4; p=0.47), even though chewed prasugrel yielded a higher metabolite concentration than whole prasugrel tablets (62.3 ± 82.6 ng/mL vs. 17.1 ± 43.5 ng/mL; p=0.016).
The authors wrote that their study supports the use of parenteral drugs, such as tirofiban and cangrelor, to achieve immediate IPA and to bridge the initial gap in platelet inhibition seen with oral P2Y12 inhibitors.
“Tirofiban, by exerting more potent and consistent inhibition of platelet aggregation, may be more effective than cangrelor in reducing the risks of acute ischemic complications, which need to be further ascertained in the context of studies powered for clinical endpoints,” the authors write.
The FABOLUS-FASTER trial is supported by a grant from Medicure Inc., which produces tirofiban.
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