TY - JOUR
T1 - Incidence of dyspnea and assessment of cardiac and pulmonary function in patients with stable coronary artery disease receiving ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET study
AU - Storey, Robert F.
AU - Bliden, Kevin P.
AU - Patil, Shankar B.
AU - Karunakaran, Arun
AU - Ecob, Rosemary
AU - Butler, Kathleen
AU - Teng, Renli
AU - Wei, Cheryl
AU - Tantry, Udaya S.
AU - Gurbel, Paul A.
N1 - Funding Information:
This work was funded by AstraZeneca LP , Wilmington, Delaware. Dr. Storey has received honoraria, consultancy fees, and/or institutional research grants from AstraZeneca , Eli Lilly , Daiichi Sankyo , Schering-Plough , The Medicines Company , Novartis , and Teva . Drs. Butler, Teng, and Wei are employees of AstraZeneca. Dr. Gurbel has received research grants, honoraria, and/or consultancy fees from Haemoscope , AstraZeneca , Schering-Plough , Medtronic , Lilly/Sankyo , Sanofi , Boston Scientific , and Bayer .
PY - 2010/7/13
Y1 - 2010/7/13
N2 - Objectives: We prospectively assessed cardiac and pulmonary function in patients with stable coronary artery disease (CAD) treated with ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET (A Multi-Centre Randomised, Double-Blind, Double-Dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of AZD6140 Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease) study. Background: Ticagrelor reduces cardiovascular events more effectively than clopidogrel in patients with acute coronary syndromes. Dyspnea develops in some patients treated with ticagrelor, and it is not known whether this is associated with changes in cardiac or pulmonary function. Methods: In all, 123 stable aspirin-treated CAD patients randomly received either ticagrelor (180 mg load, then 90 mg twice daily; n = 57), clopidogrel (600 mg load, then 75 mg daily; n = 54), or placebo (n = 12) for 6 weeks in a double-blind, double-dummy design. Electrocardiography, echocardiography, serum N-terminal pro-brain natriuretic peptide, and pulmonary function tests were performed before (baseline) and 6 weeks after drug administration and/or after development of dyspnea. Results: After drug administration, dyspnea was reported by 38.6%, 9.3%, and 8.3% of patients in the ticagrelor, clopidogrel, and placebo groups, respectively (p < 0.001). Most instances were mild and/or lasted <24 h, although 3 patients discontinued ticagrelor because of dyspnea. Eight of 22 and 17 of 22 ticagrelor-treated patients experiencing dyspnea did so within 24 h and 1 week, respectively, after drug administration. In all treatment groups, and in ticagrelor-treated patients with dyspnea, there were no significant changes between baseline and 6 weeks in any of the cardiac or pulmonary function parameters. Conclusions: Dyspnea is commonly associated with ticagrelor therapy, but was not associated in this study with any adverse change in cardiac or pulmonary function. (A Multi-Centre Randomised, Double-Blind, Double-Dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of AZD6140 Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease [ONSET/OFFSET]; NCT00528411)
AB - Objectives: We prospectively assessed cardiac and pulmonary function in patients with stable coronary artery disease (CAD) treated with ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET (A Multi-Centre Randomised, Double-Blind, Double-Dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of AZD6140 Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease) study. Background: Ticagrelor reduces cardiovascular events more effectively than clopidogrel in patients with acute coronary syndromes. Dyspnea develops in some patients treated with ticagrelor, and it is not known whether this is associated with changes in cardiac or pulmonary function. Methods: In all, 123 stable aspirin-treated CAD patients randomly received either ticagrelor (180 mg load, then 90 mg twice daily; n = 57), clopidogrel (600 mg load, then 75 mg daily; n = 54), or placebo (n = 12) for 6 weeks in a double-blind, double-dummy design. Electrocardiography, echocardiography, serum N-terminal pro-brain natriuretic peptide, and pulmonary function tests were performed before (baseline) and 6 weeks after drug administration and/or after development of dyspnea. Results: After drug administration, dyspnea was reported by 38.6%, 9.3%, and 8.3% of patients in the ticagrelor, clopidogrel, and placebo groups, respectively (p < 0.001). Most instances were mild and/or lasted <24 h, although 3 patients discontinued ticagrelor because of dyspnea. Eight of 22 and 17 of 22 ticagrelor-treated patients experiencing dyspnea did so within 24 h and 1 week, respectively, after drug administration. In all treatment groups, and in ticagrelor-treated patients with dyspnea, there were no significant changes between baseline and 6 weeks in any of the cardiac or pulmonary function parameters. Conclusions: Dyspnea is commonly associated with ticagrelor therapy, but was not associated in this study with any adverse change in cardiac or pulmonary function. (A Multi-Centre Randomised, Double-Blind, Double-Dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of AZD6140 Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease [ONSET/OFFSET]; NCT00528411)
KW - ADP
KW - AUC
KW - C
KW - CAD
KW - CYP
KW - FEV
KW - FVC
KW - adenosine diphosphate
KW - area-under-the-plasma concentration time curve over 8 hours
KW - coronary artery disease
KW - cytochrome P450
KW - forced expiratory volume at 1 s
KW - forced vital capacity
KW - maximum plasma drug concentration
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U2 - 10.1016/j.jacc.2010.01.062
DO - 10.1016/j.jacc.2010.01.062
M3 - Article
C2 - 20620737
AN - SCOPUS:77955110385
SN - 0735-1097
VL - 56
SP - 185
EP - 193
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 3
ER -