Cangrelor vs. Standard Therapy to Achieve Optimal Management of Platelet Inhibition - CHAMPION PHOENIX

Oct 10, 2018
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Presenter/Author:
Antonio Gutierrez, MD
Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Christopher P. Cannon, MD, FACC; Kim A. Eagle, MD, MACC
Trial Sponsor:
The Medicines Company
Date Presented:
08/30/2016
Date Published:
09/09/2018
Date Updated:
10/10/2018
Original Posted Date:
03/10/2013
References

Contribution To Literature:

The CHAMPION PHOENIX trial showed that the use of cangrelor reduced early ischemic events after PCI, including stent thrombosis, compared with clopidogrel.

Description:

The goal of the trial was to evaluate treatment with the intravenous adenosine diphosphate (ADP) receptor antagonist cangrelor compared with the oral ADP receptor antagonist clopidogrel among patients undergoing percutaneous coronary intervention (PCI).

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel
  • Stratified

Patient Populations:

  • Patients ≥18 years of age with stable or unstable coronary artery disease undergoing PCI
  • Number of enrollees: 11,145
  • Duration of follow-up: 30 days
  • Mean patient age: 64 years
  • Percentage female: 29%

Exclusion Criteria:

  • Use of an ADP receptor antagonist or abciximab 7 days prior to randomization
  • Use of eptifibatide, tirofiban, or fibrinolytic therapy 12 hours prior to randomization

Primary Endpoints:

  • Death, MI, ischemia-driven revascularization, or stent thrombosis at 48 hours
  • GUSTO severe bleeding at 48 hours

Secondary Endpoints:

  • Stent thrombosis at 48 hours
  • Death, MI, ischemia-driven revascularization, or stent thrombosis at 30 days

Drug/Procedures Used:

Patients with stable or unstable coronary artery disease undergoing PCI were randomized to intravenous cangrelor 30 µg/kg bolus, then 4 µg/kg/min for the duration of the PCI plus placebo pill (n = 5,472) versus clopidogrel plus placebo bolus/infusion (n = 5,470).

The loading dose and timing of clopidogrel was determined by the operator, at a dose of 300 or 600 mg.

All patients received aspirin and clopidogrel 75 mg within 48 hours of PCI. Choice of antithrombin agent was left to the discretion of the operator. Glycoprotein IIb/IIIa inhibitors were discouraged except for rescue therapy.

Principal Findings:

Overall 11,145 patients were randomized. The mean age was 64 years, 29% were women, 28% had diabetes, 5% had prior stroke/transient ischemic attack (TIA), 57% had stable angina, 25% had non-ST-segment elevation myocardial infarction (NSTEMI), and 18% had STEMI. Unfractionated heparin was used in 78% of participants. Drug-eluting stents were used in 56%. Radial artery access site was selected for PCI in 26%.

In the clopidogrel group, 63% received the loading dose before PCI (26% received a 300 mg loading dose, and 74% received a 600 mg loading dose).

The primary outcome of death, MI, ischemia-driven revascularization, or stent thrombosis at 48 hours occurred in 4.7% of the cangrelor group vs. 5.9% of the clopidogrel group (p = 0.005). This association remained the same among 2,059 subjects treated with bivalirudin (odds ratio 0.68, p = 0.047). There was no evidence for treatment interaction among multiple tested subgroups (including stable angina vs. acute coronary syndrome, gender, type of antithrombin agent, radial artery access site, 300 or 600 mg loading dose of clopidogrel, loading dose of clopidogrel pre- or post-PCI, or lesion complexity), except possibly a history of peripheral arterial disease (PAD). The primary composite outcome at 30 days occurred in 6.0% of the cangrelor group vs. 7.0% of the clopidogrel group (p = 0.03).

- Stent thrombosis at 48 hours: 0.8% vs. 1.4% (p = 0.01), respectively, for cangrelor vs. clopidogrel

- Intraprocedural stent thrombosis increased the hazard of 48-hour (HR = 11.85) and 30-day (HR = 9.65) adverse ischemic events compared with no intraprocedural stent thrombosis.

- MI at 48 hours: 3.8% vs. 4.7% (p = 0.02), respectively, for cangrelor vs. clopidogrel. This association remained the same regardless of the definition used to define MI.

- Ischemia-driven revascularization at 48 hours: 0.5% vs. 0.7% (p = 0.22), respectively, for cangrelor vs. clopidogrel

- Severe bleeding at 48 hours: 0.16% vs. 0.11% (p = 0.44), respectively, for cangrelor vs. clopidogrel

- Transient dyspnea: 1.2% vs. 0.3% (p < 0.001), respectively, for cangrelor vs. clopidogrel

In a pooled analysis of the three CHAMPION trials (n = 24,910), the composite efficacy endpoint of death, MI, ischemia-driven revascularization, or stent thrombosis at 48 hours occurred in 3.8% of the cangrelor group vs. 4.7% in the control group (p = 0.0007). Stent thrombosis: 0.5% vs. 0.8% (p = 0.0008), respectively. The composite safety endpoint of GUSTO severe or life-threatening bleeding at 48 hours occurred in 0.2% of the cangrelor group vs. 0.2% in the control group (p = 0.49). ACUITY major bleeding: 4.2% vs. 2.8% (p < 0.001), GUSTO minor bleeding: 16.8% vs. 13.0% (p < 0.001), respectively.

Among STEMI patients, the risk of the primary outcome was the same for on-hours presentation versus after-hours presentation (RR 1.00, p = 0.99)

Interpretation:

Among a broad range of patients with stable or unstable coronary artery disease undergoing PCI, the use of cangrelor reduced early ischemic events, including stent thrombosis and MI, compared with clopidogrel. This finding remained the same among multiple subgroups including access site, and lesion complexity. Ischemic benefit was accomplished without an excess in severe bleeding. Among the clopidogrel group, the majority of patients received this medication pre-PCI, and at a dose of 600 mg. It is uncertain if the results would have been the same had prasugrel or ticagrelor been used as the oral agent. Intravenous cangrelor represents an alternative strategy for antiplatelet therapy during PCI.

References:

Stone GW, Généreux P, Harrington RA, et al. Impact of lesion complexity on peri-procedural adverse events and the benefit of potent intravenous platelet adenosine diphosphate receptor inhibition after percutaneous coronary intervention: core laboratory analysis from 10,854 patients from the CHAMPION PHOENIX trial. Eur Heart J 2018;Sep 9:[Epub ahead of print].

Abtan J, Steg PG, Stone GW, et al. Efficacy and Safety of Cangrelor in Preventing Periprocedural Complications in Patients With Stable Angina and Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: The CHAMPION PHOENIX Trial. JACC Cardiovasc Interv 2016;9:1905-13.

Selvaraj S, Bhatt DL, Stone GW, et al. “Off-Hours” Versus “On-Hours” Presentation in ST-Segment Elevation Myocardial Infarction: Findings From CHAMPION PHOENIX. J Am Coll Cardiol 2016;68:2385-7.

Presented by Dr. Senthil Selvaraj at the European Society of Cardiology Congress, Rome, Italy, August 30, 2016.

Cavender MA, Bhatt DL, Stone GW, et al. Consistent Reduction in Peri-Procedural Myocardial Infarction With Cangrelor as Assessed by Multiple Definitions: Findings From CHAMPION PHOENIX (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition). Circulation 2016;134:723-33.

O’Donoghue ML, Bhatt DL, Stone GW, et al. Efficacy and Safety of Cangrelor in Women Versus Men During Percutaneous Coronary Intervention: Insights From the Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION PHOENIX) Trial. Circulation 2016;133:248-55.

White HD, Bhatt DL, Gibson CM, et al. Outcomes With Cangrelor Versus Clopidogrel on a Background of Bivalirudin: Insights From the CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI]). JACC Cardiovasc Interv 2015;8:424-33.

Presented by Dr. J. Antonio Gutierrez at the European Society of Cardiology Congress, London, August 31, 2015.

Généreux P, Stone GW, Harrington RA, et al. Impact of Intra-Procedural Stent Thrombosis During Percutaneous Coronary Intervention: Insights From the CHAMPION PHOENIX Trial. J Am Coll Cardiol 2014;63:619-29.

Presented by Dr. Philippe Généreux at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2013), San Francisco, CA, October 28, 2013.

Steg PG, Bhatt DL, Hamm CW, et al., on behalf of the CHAMPION Investigators. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data. Lancet 2013;382:1981-92.

Presented by Dr. Christian Hamm at the European Society of Cardiology Congress, Amsterdam, Holland, September 3, 2013.

Bhatt DL, Stone GW, Mahaffey KW, et al., on behalf of the CHAMPION PHOENIX Investigators. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med 2013;368:1303-13.

Presented by Dr. Deepak Bhatt at ACC.13, San Francisco, March 10, 2013.

Keywords: Coronary Artery Disease, Myocardial Infarction, Stroke, Ischemic Attack, Transient, Angina, Stable, Drug-Eluting Stents, Heparin, Peripheral Arterial Disease, Ticlopidine, Piperazines, Dyspnea, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Thrombosis, Diabetes Mellitus, Platelet Glycoprotein GPIIb-IIIa Complex, ESC Congress


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