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

• Published in: Journal of the American College of Cardiology 2010-07, Vol.56 (3), p.185-193
• Main Authors: Storey, Robert F., MD, DM, Bliden, Kevin P., BS, Patil, Shankar B., MD, Karunakaran, Arun, MD, Ecob, Rosemary, MA, Butler, Kathleen, MD, MS, Teng, Renli, PhD, Wei, Cheryl, PhD, MS, Tantry, Udaya S., MD, Gurbel, Paul A., MD
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Adenosine - adverse effects; Adenosine - analogs & derivatives; Aged; Angina pectoris; Aspirin - therapeutic use; Biological and medical sciences; Blood pressure; Carbon monoxide; Cardiology; Cardiology. Vascular system; Cardiovascular; Cardiovascular disease; coronary disease; Coronary Disease - drug therapy; Coronary Disease - physiopathology; Coronary heart disease; Coronary vessels; Double-Blind Method; Drug dosages; Drug therapy; Dyspnea - chemically induced; Female; Heart; Heart - drug effects; Heart attacks; Heart rate; Humans; Internal Medicine; Lung - drug effects; Male; Medical sciences; Middle Aged; pharmacology; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - therapeutic use; platelets; Pneumology; Prospective Studies; Respiratory system : syndromes and miscellaneous diseases; thrombosis; Ticlopidine - analogs & derivatives; Ticlopidine - therapeutic use; Ventilation
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2010.01.062

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