Variation in Patient Profiles and Outcomes in US and Non-US Subgroups of the Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) PHOENIX Trial.
The Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) PHOENIX trial demonstrated superiority of cangrelor in reducing ischemic events at 48 hours in patients undergoing percutaneous coronary intervention compared with clopidogrel.



We analyzed all patients included in the modified intention-to-treat analysis in US (n=4097; 37.4%) and non-US subgroups (n=6845; 62.6%). The US cohort was older, had a higher burden of cardiovascular risk factors, and had more frequently undergone prior cardiovascular procedures. US patients more frequently underwent percutaneous coronary intervention for stable angina (77.9% versus 46.2%). Almost all US patients (99.1%) received clopidogrel loading doses of 600 mg, whereas 40.5% of non-US patients received 300 mg. Bivalirudin was more frequently used in US patients (56.7% versus 2.9%). At 48 hours, rates of the primary composite end point were comparable in the US and non-US cohorts (5.5% versus 5.2%; P=0.53). Cangrelor reduced rates of the primary composite end point compared with clopidogrel in US (4.5% versus 6.4%; odds ratio 0.70 [95% confidence interval 0.53-0.92]) and in non-US patients (4.8% versus 5.6%; odds ratio 0.85 [95% confidence interval 0.69-1.05]; interaction P=0.26). Similarly, rates of the key secondary end point, stent thrombosis, were reduced by cangrelor in both regions. Rates of Global Use of Strategies to Open Occluded Arteries (GUSTO)-defined severe bleeding were low and not significantly increased by cangrelor in either region.



Despite broad differences in clinical profiles and indications for percutaneous coronary intervention by region in a large global cardiovascular clinical trial, cangrelor consistently reduced rates of ischemic end points compared with clopidogrel without an excess in severe bleeding in both the US and non-US subgroups.



URL: http://www.clinicaltrials.gov. Unique identifier: NCT01156571.
From the Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (M.V., D.L.B); Stanford University Medical School, CA (R.A.H., K.W.M.); Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.); FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France, and NHLI, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (C.M.G.); Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.); Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W).
Muthiah
M
Vaduganathan
From the Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (M.V., D.L.B); Stanford University Medical School, CA (R.A.H., K.W.M.); Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.); FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France, and NHLI, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (C.M.G.); Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.); Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W).
Robert A
RA
Harrington
From the Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (M.V., D.L.B); Stanford University Medical School, CA (R.A.H., K.W.M.); Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.); FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France, and NHLI, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (C.M.G.); Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.); Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W).
Gregg W
GW
Stone
From the Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (M.V., D.L.B); Stanford University Medical School, CA (R.A.H., K.W.M.); Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.); FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France, and NHLI, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (C.M.G.); Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.); Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W).
Ph Gabriel
PG
Steg
From the Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (M.V., D.L.B); Stanford University Medical School, CA (R.A.H., K.W.M.); Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.); FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France, and NHLI, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (C.M.G.); Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.); Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W).
C Michael
CM
Gibson
From the Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (M.V., D.L.B); Stanford University Medical School, CA (R.A.H., K.W.M.); Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.); FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France, and NHLI, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (C.M.G.); Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.); Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W).
Christian W
CW
Hamm
From the Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (M.V., D.L.B); Stanford University Medical School, CA (R.A.H., K.W.M.); Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.); FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France, and NHLI, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (C.M.G.); Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.); Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W).
Matthew J
MJ
Price
From the Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (M.V., D.L.B); Stanford University Medical School, CA (R.A.H., K.W.M.); Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.); FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France, and NHLI, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (C.M.G.); Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.); Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W).
Jayne
J
Prats
From the Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (M.V., D.L.B); Stanford University Medical School, CA (R.A.H., K.W.M.); Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.); FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France, and NHLI, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (C.M.G.); Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.); Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W).
Efthymios N
EN
Deliargyris
From the Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (M.V., D.L.B); Stanford University Medical School, CA (R.A.H., K.W.M.); Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.); FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France, and NHLI, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (C.M.G.); Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.); Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W).
Kenneth W
KW
Mahaffey
From the Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (M.V., D.L.B); Stanford University Medical School, CA (R.A.H., K.W.M.); Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.); FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France, and NHLI, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (C.M.G.); Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.); Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W).
Harvey D
HD
White
From the Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (M.V., D.L.B); Stanford University Medical School, CA (R.A.H., K.W.M.); Columbia University Medical Center and the Cardiovascular Research Foundation, New York City, NY (G.W.S.); FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, France, and NHLI, Imperial College, Royal Brompton Hospital, London, UK (P.G.S.); Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (C.M.G.); Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany (C.W.H.); Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA (M.J.P.); The Medicines Company, Parsippany, NJ (J.P., E.N.D.); and Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W). dlbhattmd@post.harvard.edu.
Deepak L
DL
Bhatt
D000249:Adenosine Monophosphate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D001938:Brazil; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D011446:Prospective Studies; D012307:Risk Factors; D013785:Thailand; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D010975:Platelet Aggregation Inhibitors; D000249:Adenosine Monophosphate; C117446:cangrelor; D000077144:Clopidogrel; D013988:Ticlopidine
antiplatelet therapy; clinical trial; international comparison; percutaneous coronary intervention; variation