Response by Gargiulo et al to Letter Regarding Article, “Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction: Primary Results of the FABOLUS FASTER Trial”
Authors: Giuseppe Gargiulo, Michael Nagler, Marco Valgimigli
Journal: Circulation (2021)

We thank Drs Angiolillo, Bhatt, and Stone for commenting on our trial. 1ur findings integrate, more than contradict, the results of the CHAMPION program (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition), where cangrelor was superior to clopidogrel for the inhibition of platelet aggregation (IPA) and prevention of ischemic events. 2 Clopidogrel does not provide IPA within the first hour or even longer among ST-segment-elevation myocardial infarction. 3Prasugrel and ticagrelor are also associated with delayed IPA in ST-segment-elevation myocardial infarction. 4Our study confirmed the superiority on IPA of cangrelor over prasugrel, either taken as integral or chewed tablets and supports the need for parenteral agents.The exploratory analysis comparing cangrelor with glycoprotein IIb/IIIa inhibitors provided intriguing findings, although, as the authors stated, they could be subject to residual bias and confounding because of unmeasured covariates, the propensity score matching was incomplete, and the program was not designed to compare cangrelor with glycoprotein IIb/IIIa inhibitors.The FABOLUS FASTER trial (Facilitation Through Aggrastat or Cangrelor Bolus and Infusion Over Prasugrel: A Multicenter Randomized Open-Label Trial in Patients With ST-Elevation Myocardial Infarction Referred for Primary Percutaneous Intervention) showed that tirofiban provided superior IPA compared with cangrelor.Whether the use of glycoprotein IIb/IIIa inhibitors translates into lower ischemic risks, including improved reperfusion and lower thrombotic complications, requires further investigation.We concur that LTA is labor intensive.However, LTA is the historical gold-standard tool for platelet function studies.The authors argue that LTA may not be the ideal assay for cangrelor because of the need for sample manipulation and time delay that could affect cangrelor binding to the P2Y12 receptor.This remains an interesting hypothesis.The authors themselves implemented LTA to measure IPA in the CHAMPION program, which showed, consistent with our results, a remarkable variability in residual platelet aggregation during cangrelor infusion. 2TA requires 2 rounds of 10-minute centrifugation to obtain platelet-rich and -poor plasma before the analysis can be performed, whereas Multiplate can be analyzed directly on whole blood but requires blood samples to stay at room temperature for 30 minutes before the analysis.Thus, LTA may provide faster results than Multiplate.Multiplate tests were carried out in a subsample of patients recruited in 2 of 3 participating centers and should therefore be interpreted with caution.We did observe some variability among patients and centers, but LTA showed no case of >90% inhibition with cangrelor, which explains the mean IPA of 34.1%.Even when considering late aggregation values of LTA, the mean IPA at 30 minutes was 41.5% with cangrelor, and Downloaded from http://ahajournals.org