Clopidogrel Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition–PLATFORM - CHAMPION PLATFORM

Sep 03, 2013
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Christopher P. Cannon, MD, FACC
Trial Sponsor:
The Medicines Company
Date Updated:
09/03/2013
Original Posted Date:
09/03/2013
References

Description:

The goal of this trial was to evaluate treatment with intravenous cangrelor compared with placebo among acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).

Hypothesis:

Intravenous cangrelor would be superior at reducing adverse events early after PCI.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel

Patients Enrolled: 5,301
Mean Follow Up: 1 year
Mean Patient Age: Median 63 years
Female: 28%

Patient Populations:

  • Patients at least 18 years of age with unstable angina or NSTEMI undergoing PCI

    Exclusions:

    • Use of a thienopyridine in the previous 7 days
    • Use of fibrinolytic therapy or glycoprotein IIb/IIIa inhibitor in the previous 12 hours
    • Planned staged PCI
    • Planned admission within 12 hours after PCI
    • STEMI
    • Pregnancy or lactation
    • Increased risk of bleeding or known bleeding disorder
    • Ischemic stroke in the previous year or any previous hemorrhagic stroke
    • Intracranial tumor or aneurysm
    • Trauma or major surgery in the previous month
    • Coagulopathy or thrombocytopenia
    • Severe hypertension

      Primary Endpoints:

      • Composite of death, MI, or urgent revascularization at 48 hours

        Secondary Endpoints:

        • Stent thrombosis
        • Death
        • MI, including Q-wave MI
        • Urgent revascularization
        • Abrupt vessel closure
        • Stroke

          Drug/Procedures Used:

          Patients naive to clopidogrel undergoing PCI were randomized to intravenous cangrelor (n = 2,656) versus placebo (n = 2,645). Patients in the cangrelor arm received a 30 µg/kg bolus and 4 µg/kg/min infusion for the duration of PCI. Both groups received clopidogrel 600 mg after PCI.

          Concomitant Medications:

          Procedurally, unfractionated heparin was used in 64%, bivalirudin in 21%, low molecular weight heparin in 18%, and a glycoprotein IIb/IIIa inhibitor in 9%.

Principal Findings:

Overall, 5,362 patients were randomized with intention-to-treat. In the cangrelor group, the median age was 63 years, 28% were women, 31% had diabetes, 35% had unstable angina, 59% had non-ST-elevation myocardial infarction (NSTEMI), and the time from admission to PCI was 7.9 hours. Drug-eluting stents were used in 39% and bare-metal stents in 57%.

The primary outcome (death, MI, or urgent revascularization) was analyzed by modified intention-to-treat, and it occurred in 7.0% of the cangrelor group versus 8.0% of the placebo group (p = 0.17). The primary outcome was reduced among those who did not have troponin elevation (4.6% vs. 7.2%, p = 0.03).

All-cause mortality was 0.2% versus 0.7% (p = 0.02), MI was 6.7% versus 7.2% (p = 0.42), urgent revascularization was 0.7% versus 0.9% (p = 0.44), stroke was 0.3% versus 0.2% (p = 0.57), and stent thrombosis was 0.2% versus 0.6% (p = 0.02).

Blood transfusion was 0.9% versus 0.6%, hematoma greater than 5 cm was 4.3% versus 2.7% (p = 0.001), ACUITY major bleeding was 5.5% versus 3.5% (p < 0.001), GUSTO severe/life-threatening bleeding was 0.3% versus 0.2% (p = 0.45), and TIMI major bleeding was 0.2% versus 0.3% (p = 0.17), respectively.

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 versus 4.7% in the control group (p = 0.0007). Stent thrombosis: 0.5% versus 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 versus 0.2% in the control group (p = 0.49). ACUITY major bleeding: 4.2% versus 2.8% (p < 0.001), GUSTO minor bleeding: 16.8% vs. 13.0% (p < 0.001), respectively.

Interpretation:

Among patients undergoing PCI for NSTE ACS the use of cangrelor during PCI was not superior to placebo. Cangrelor did not reduce death, MI, or urgent revascularization at 48 hours, although there was evidence for efficacy in a pooled analysis. Prespecified secondary endpoints of all-cause mortality and stent thrombosis were reduced with the use of cangrelor. Severe/life-threatening bleeding and transfusions were similar between the groups; however, there were more groin hematomas in the cangrelor group.

Study enrollment was terminated early when it was determined that the trial would be unlikely to show superiority for cangrelor. This trial complements the CHAMPION PCI trial, which compared cangrelor to clopidogrel prior to PCI. Further study is needed to determine subgroups of patients that may benefit from this agent. The possible reduction in early death and stent thrombosis with cangrelor also supports the importance of pre-procedural dual-anti-platelet therapy.

References:

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, Lincoff M, Gibson CM, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009;Nov 15:[Epub ahead of print].

Presented by Dr. Deepak Bhatt at the American Heart Association Scientific Sessions, Orlando, FL, November 15, 2009.

Keywords: Myocardial Infarction, Stroke, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Drug-Eluting Stents, Ticlopidine, Blood Platelets, Hematoma, Groin, Percutaneous Coronary Intervention, Blood Transfusion, Thrombosis, Diabetes Mellitus, Hemorrhage, Troponin


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