Cangrelor inferior to tirofiban for platelet aggregation inhibition during PCI
Click Here to Manage Email Alerts
Cangrelor resulted in inferior platelet aggregation inhibition compared with tirofiban in patients with STEMI who were undergoing PCI, the FABOLUS-FASTER study found.
The study, which was presented at the virtual PCR e-Course and simultaneously published in Circulation, also found that cangrelor (Kengreal, Chiesi) and tirofiban (Aggrastat, Medicure) generated greater platelet aggregation inhibition compared with chewed prasugrel (Effient, Daiichi Sankyo/Eli Lilly).
“The study shows for the first time that tirofiban is roughly threefold more potent in P2Y12 pathway inhibition than cangrelor, which was associated with surprisingly low levels of platelet inhibition,” Marco Valgimigli, MD, PhD, professor of cardiology and deputy chief at Cardiocentro Lugano in Switzerland, told Healio. “Chewed prasugrel has slightly better inhibition upfront, but there was mainly a marginal difference with integer prasugrel, which did not reach statistical significance. Hence, the bottom line is that even chewing oral P2Y12 inhibitors tablets does not really help to mitigate the platelet reactivity in the acute phase of a STEMI and that parenteral drugs are needed, but their comparative effectiveness differs substantially.”
Patients with STEMI
In this multicenter, open-label, randomized study, researchers analyzed data from 122 patients (mean age, 64 years; 76% men) with STEMI who underwent primary PCI between July 4, 2017, and Aug. 26, 2019, in three centers in Switzerland and Italy.
Patients were assigned standard regimen of tirofiban (n = 40; mean age, 63 years; 78% men), standard regimen of cangrelor (n = 40; mean age, 66 years; 73% men) or 60 mg prasugrel at PCI initiation. The prasugrel group were also assigned chewed (n = 21; mean age, 65 years; 90% men) or integral tablet administration (n = 21; mean age, 61 years; 67% men).
The primary endpoint was inhibition of platelet aggregation at 30 minutes at light transmittance aggregometry with 20 µmol/L of adenosine diphosphate.
Compared with tirofiban, cangrelor did not meet noninferiority. Patients assigned tirofiban had superior platelet aggregation inhibition compared with those assigned cangrelor (95 vs. 34.1; P < .001).
Tirofiban and cangrelor were superior to chewed prasugrel (10.5; P for both < .001). Compared with integral prasugrel, chewed prasugrel did not reach superior platelet aggregation inhibition (6.3; P = .47), although it resulted in higher active metabolite concentration (62.3 ng/mL vs. 17.1 ng/mL; P = .016).
“The data clearly speak for the fact that tirofiban is a much more potent antiplatelet agent in the acute phase of STEMI and should probably be preferred to cangrelor unless the bleeding risk remains a matter of concern, which, in the acute phase of STEMI, is clearly not frequently the case, whereas the ischemic risk is prevailing,” Valgimigli said in an interview.
Additional research
Valgimigli said more research is needed in this area. “A study powered for overcome data would be highly desirable. A modern use of glycoprotein IIb/IIIa inhibitors consisting in bolus followed by no or very short infusion has a high potential for optimizing the ischemic risk without an excess of bleeding complications,” he said.
Reference:
- Valgimigli M, et al. STEMI Interventions: First-in-Man and Novel Pharmacological Strategies. Presented at: PCR e-Course; June 25-27, 2020 (virtual meeting).
Perspective
Back to Top
Dominick J. Angiolillo, MD, PhD, FACC, FESC, FSCAI
Patients with STEMI undergoing primary PCI are characterized by a delay in the onset of the effects of oral antiplatelet therapies. This underscores the need to identify strategies associated with more prompt and potent antiplatelet effects in these high-risk patients. To this extent, there have been ways to look at oral formulations to accelerate absorption, such as crushing or chewing them. Nevertheless, it is a limiting factor that the oral drugs need to be absorbed in the gut and go into the circulation before their effects appear. There is an inevitable delay.
This leads us to look into IV therapies. Currently there are two, one with cangrelor and one with a glycoprotein IIb/IIIa inhibitor. These drugs are very different. Cangrelor blocks the P2Y12 receptor and the GPI blocks the IIb/IIIa receptor. Each has been previously studied in the setting of STEMI for how they immediately enhance platelet inhibition. This is the first study comparing the two IV therapies, which is very important. Moreover, this was a very difficult study to conduct as it required pharmacodynamic assessments to be performed in an acute setting.
In this study, noninferiority of cangrelor compared with the GPI tirofiban was not met and tirofiban had significantly lower levels of platelet reactivity, ie, a greater degree of platelet inhibition. This was a surprise. What was shown with the GPI was expected. But the level of platelet inhibition observed with cangrelor were modest and much lower than anticipated in the study assumptions, and lower than what was shown in other studies.
The question becomes whether the findings were an outlier compared with other ways of testing the effect of cangrelor. The primary endpoint was based on light transmittance aggregometry. But when the authors used another assay, multiple electrode aggregometry (Multiplate, Roche), there was indeed more profound platelet inhibition with cangrelor. Was the assay misleading to interpret the findings? Light transmittance aggregometry has been considered the gold standard for assessment of platelet aggregation. But because cangrelor has a very short half-life and is very unstable, and performing light transmittance aggregometry requires time and sample manipulation, we cannot exclude that there could have been an impact of the assay itself on the findings.
We need to have a better understanding of the impact of different assays on the pharmacodynamic effects of cangrelor. This is an area of unmet need. We now have evidence from some studies showing profound platelet inhibition with most assays, yet with the assay used for the primary endpoint in FABOLUS-FASTER, there was a different finding. There is room for studies defining which is the best to assess the effects of cangrelor. These findings highlight the need to have standardized protocols for pharmacodynamic assessments based on specific antithrombotic drugs being used.
Collapse
Click Here to Manage Email Alerts