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.
OBJECTIVE
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).
Storey
Robert F
RF
Department of Cardiovascular Science, University of Sheffield, and NIHR Cardiovascular Biomedical Research Unit, Sheffield, United Kingdom. r.f.storey@sheffield.ac.uk
Bliden
Kevin P
KP
Patil
Shankar B
SB
Karunakaran
Arun
A
Ecob
Rosemary
R
Butler
Kathleen
K
Teng
Renli
R
Wei
Cheryl
C
Tantry
Udaya S
US
Gurbel
Paul A
PA
D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004417:Dyspnea / Q000139:chemically induced*; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D011446:Prospective Studies; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin