FABOLUS FASTER Trial Review: Cangrelor, Tirofiban and Chewed or Standard Prasugrel Regimens in Patients with ST-Segment Elevation Myocardial Infarction
Which one is Fabulous?
The investigator sought to determine the acute pharmacodynamic effects of cangrelor, tirofiban or prasugrel, as integral or chewed tablets, in STEMI patients undergoing primary PCI.
Background: Standard administration of newer oral P2Y12 inhibitors provides suboptimal early inhibition of platelet aggregation (IPA) in ST-Segment Elevation Myocardial Infarction (STEMI) patients undergoing primary PCI. In this regard, parenteral anti-platelet therapies such as cangrelor or tirofiban may provide an advantage in STEMI clinical scenario.
Objective: The investigator sought to determine the acute pharmacodynamic effects of cangrelor, tirofiban or prasugrel, as integral or chewed tablets, in STEMI patients undergoing primary PCI.
Methodology1
- Investigator-initiated, multicenter, open-label, randomized study (NCT02978040)
- P2Y12-naïve STEMI patients were randomly allocated (1:1:1) to cangrelor (n=40), tirofiban (n=40), both administered as bolus and 2h infusion followed by 60 mg of prasugrel, or 60 mg loading dose of prasugrel (n=42). The latter group underwent an immediate 1:1 sub-randomization to chewed (n=21), or integral (n=21) tablets administration. (Figure 1).
- Primary outcome: is platelet inhibition assessed with light transmission aggregometry (LTA) in platelet-rich plasma with the addition of adenosine diphosphate (ADP) 20 µmol/l at 30 minutes from drug administration (n=21) tablets administration.
- Non-inferiority of cangrelor compared with tirofiban,
- Superiority of both tirofiban and cangrelor compared with chewed prasugrel,
- Superiority of chewed prasugrel as compared with integral prasugrel.
Figure 1. FABOLUS FASTER Trial patients flow chart
- Essential results2 (Figure 2)
- At 30 min, cangrelor did not satisfy non-inferiority compared with tirofiban, which yielded superior IPA over cangrelor (IPA: 95.0±8.9 vs. 34.1±22.5; P<0.001) (Non-inferiority was not achieved);
- Cangrelor or tirofiban were both superior to chewed prasugrel (IPA: 10.5±11.0, P<0.001 for both comparisons) (Superiority was achieved),
- Chewed prasugrel did not provide higher IPA over integral prasugrel (6.3±11.4; P=0.47), despite yielding higher prasugrel's active metabolite concentration (ng/ml; 62.3±82.6 vs. 17.1±43.5; P=0.016) (Superiority was not achieved).
Figure 2. The primary endpoint of the FABOLUS FASTER Trial
Comments:
- We need to provide a strong IPA in the STEMI patient. However oral P2Y12 inhibitors (even chewed) are not efficient in this task in the early stage.
- Among parental drugs, tirofiban demonstrated superior efficacy than cangrelor, suggesting that GPI might be preferable over cangrelor to minimize the risk of acute ischemic complications, mainly stent thrombosis.
- Large-scale trials re-assessing the comparative risk-benefit of short infusion of parenteral platelet inhibitors such as cangrelor or GPI compared to newer oral P2Y12 receptor blockers alone in contemporary primary PCI practice remain desirable.
Other sources of information:
- View the presentation of the FABOLUS FASTER Trial by Marco Valgimigli at #PCReCourse 2020
- Christoph K. Naber provides some insight of the FABOLUS FASTER trial in the session “STEMI interventions - First-in-Man and novel pharmacological strategies”
#CardioPoll on @Twitter
The senior author of the trial, Prof. Marco Valgimigli (@vlgmrc), published this interesting poll on Twitter. Please provide us feedback on how this trial, presented in the #PCReCourse, may impact your daily clinical practice.
The fabulous faster study showed cangrelor provides 3-fold lower inhibition of the P2Y12 pathway compared to tirofiban. Chewed prasugrel was any better than integer prasugrel. What are the implications for practice ?
— Marco Valgimigli (@vlgmrc) June 28, 2020
References:
1. Gargiulo G, Esposito G, Cirillo P, Nagler M, Minuz P, Campo G, Gragnano F, Manavifar N, Piccolo R, Avvedimento M, Tebaldi M, Wahl A, Hunziker L, Billinger M, Heg D, Windecker S and Valgimigli M. 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 (FABOLUS FASTER) Trial: Design and Rationale : The FABOLUS FASTER Trial. J Cardiovasc Transl Res. 2020.
2. Gargiulo G, Esposito G, Cirillo P, Nagler M, Minuz P, Campo G, Gragnano F, Manavifar N, Piccolo R, Avvedimento M, Tebaldi M, Wahl A, Hunziker L, Billinger M, Heg D, Windecker S and Valgimigli M. Cangrelor, Tirofiban and Chewed or Standard Prasugrel Regimens in Patients with ST-Segment Elevation Myocardial Infarction: Primary Results of the FABOLUS FASTER Trial. Circulation 27 Jun 2020https://doi.org/10.1161/CIRCULATIONAHA.120.046928.
No comments yet!