CANgrelor and Crushed TICagrelor in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention - CANTIC

Jan 29, 2019
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Chiesi
Date Published:
01/11/2019
Date Updated:
01/29/2019
Original Posted Date:
01/29/2019
References

Contribution To Literature:

Among patients undergoing primary PCI for STEMI and receiving crushed ticagrelor, cangrelor lowers platelet reactivity as early as 5 minutes after infusion compared with placebo; this difference was maintained for the duration of infusion (2 hours).

Description:

The goal of the trial was to assess the safety and efficacy of cangrelor compared with a crushed oral P2Y12 inhibitor among patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Study Design

Following angiography and confirmation of need to proceed with primary PCI, patients were randomized in a 1:1 fashion to either cangrelor 30 mcg/kg bolus followed by 4 mcg/kg/min infusion (n = 25) or matching placebo (n = 25). This infusion was maintained for 2 hours. Simultaneous with the intravenous infusion, patients received crushed ticagrelor 180 mg in both arms.

  • Total number screened: 99
  • Total number of enrollees: 50
  • Duration of follow-up: 30 minutes
  • Mean patient age: 60 years
  • Percentage female: 34%
  • Percentage with diabetes: 36%

Inclusion criteria:

  • P2Y12 inhibitor naïve
  • Presentation with STEMI with intent to undergo primary PCI

Exclusion criteria:

  • Use of glycoprotein IIb/IIIa inhibitors (GPIs)

Other salient features/characteristics:

  • Prior PCI: 20%
  • Location of MI: anterior 40%, inferior 53%

Principal Findings:

The primary outcome, P2Y12 reaction unit (PRU) levels at 30 minutes using VerifyNow, between cangrelor + ticagrelor vs. ticagrelor alone, was 63 vs. 214 (p < 0.01). PRU levels dropped by 5 minutes and remained lower until the end of the 2-hour infusion.

Secondary outcomes for cangrelor + ticagrelor vs. ticagrelor:

  • High on-treatment platelet reactivity at end of PCI: 0% vs. 33% (p < 0.01)

Interpretation:

The results of this trial indicate that, among patients undergoing primary PCI for STEMI and receiving crushed ticagrelor, cangrelor lowers platelet reactivity as early as 5 minutes after infusion compared with placebo. This difference was maintained for the duration of infusion (2 hours). In parallel, the incidence of high on-treatment platelet reactivity was higher in the arm that received crushed ticagrelor alone. No clinical endpoints were studied in this trial.

Although this is a small trial, results are interesting and provide pharmacodynamic insight into the efficacy of cangrelor compared with crushed ticagrelor, which is considered the fastest acting formulation of ticagrelor. Unfortunately, the use of GPI was not permitted, and it is unclear whether ticagrelor + GPI would have similar pharmacodynamic effects as ticagrelor + cangrelor. In the CHAMPION PHOENIX trial, cangrelor was noted to have superior ischemic outcomes compared with clopidogrel, which is less potent than ticagrelor.

References:

Franchi F, Rollini F, Rivas A, et al. Platelet Inhibition With Cangrelor and Crushed Ticagrelor in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results of the CANTIC Study. Circulation 2019;Jan 11:[Epub ahead of print].

Clinical Topics: Acute Coronary Syndromes, Cardiovascular Care Team, Invasive Cardiovascular Angiography and Intervention, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Acute Coronary Syndrome, Adenosine, Adenosine Monophosphate, Angiography, Blood Platelets, Infusions, Intravenous, Myocardial Infarction, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Receptors, Purinergic P2Y12, Ticlopidine


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