Tirofiban Bests Cangrelor for Inhibiting Platelet Aggregation in FABOLUS-FASTER Study

This article was originally published on HCPLive.com.

Results of the FABOLUS-FASTER trial indicate tirofiban may be more effective than cangrelor in reducing risk of acute ischemic complications when used for bridging platelet inhibition in heart attack patients undergoing percutaneous coronary intervention (PCI).

Presented as part of PCR e-course due to the cancellation of EuroPCR 2020, results of the FABOLUS-FASTER trial, which examined the pharmacodynamic effects of cangrelor and tirofiban as well as chewed and integral prasugrel, support the use of parenteral drugs for achieving immediate inhibition of platelet aggregation (IPA) and bridging the inhibition gap often seen with oral P2Y12 inhibitors.

“Our study is the first, to the best of our knowledge, to compare the pharmacodynamic effects of cangrelor, a direct parenteral P2Y12 inhibitor, with tirofiban, a glycoprotein IIb/IIIa inhibitor, as well as the pharmacodynamic and pharmacokinetic effects of a 60 mg chewed or integral pill intake of prasugrel,” investigators wrote.

While new oral P2Y12 inhibitors have revolutionized care, clinicians often find the oral agents are unable to provide optimal early IPA in ST-segment elevation myocardial infarction (STEMI) patients undergoing PCI. To investigate the potential of the aforementioned agents for addressing this issue, the investigator-initiated FABOLUS-FASTER trial was designed as a multicenter, open-label, randomized trial.

A total of 122 P2Y12-naive STEMI patients were included in the study and these patients underwent randomization in a 1:1:1 ratio to receive cangrelor (n=40), tirofiban (n=40), or 60 mg loading dose of prasugrel (n=42). Those randomized to prasugrel were subrandomized to chewed (n=21) or integral (n=21) tablets administration. Of note, patients randomized to cangrelor or tirofiban had the agents administered as bolus and a 2 hour infusion followed by 60 mg of prasugrel.

The study was powered to test the noninferiority of cangrelor compared with tirofiban using a noninferiority margin of 9%, the superiority of both tirofiban and cangrelor compare with chewed prasugrel, and the superiority of chewed prasugrel compared with integral prasugrel for the primary endpoint of 30-minute IPA. Investigators measured 30-minute IPA at light transmittance aggregometry in response to 20 umol/L adenosine diphosphate.

Of the 122 patients included in the study, the mean age was 64 years, 20% had diabetes, and 52% presented within 3 hours of symptom onset. Most patients included in the study presented in sinus rhythm, 4% had a prior cardiac arrest, and 4% required infusion of vasopressors.

At 30 minutes, cangrelor did not achieve noninferiority with tirofiban, which investigators noted achieved superior IPA over cangrelor (95.0±9.0 vs 34.1±22.5; P <.001). Results of the analysis also indicated cangrelor and tirofiban were both superior to chewed prasugrel (10.5±11.0, P <.001 for both comparisons) and chewed prasugrel did not achieve superior IPA over integral prasugrel (6.3±11.4; P=.47).

Investigators noted while chewed prasugrel did not provide greater IPA than integral prasugrel it provided greater active metabolite bioavailability up to an hour after drug administration (62.3±82.6 ng/ml vs 17.1±43.5 ng/ml; P=.016).

This study, “Cangrelor, tirofiban and chewed or standard prasugrel regimens in patients with ST-segment elevation myocardial infarction: primary results of the FABOLUS FASTER trial,” was presented as part of PCR e-course and published in Circulation.