TY - JOUR
T1 - Prior smoking status, clinical outcomes, and the comparison of ticagrelor with clopidogrel in acute coronary syndromes - Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial
AU - Cornel, Jan H.
AU - Becker, Richard C.
AU - Goodman, Shaun G.
AU - Husted, Steen
AU - Katus, Hugo
AU - Santoso, Anwar
AU - Steg, Gabriel
AU - Storey, Robert F.
AU - Vintila, Marius
AU - Sun, Jie L.
AU - Horrow, Jay
AU - Wallentin, Lars
AU - Harrington, Robert
AU - James, Stefan
N1 - Funding Information:
Dr Cornel: advisory board fees from AstraZeneca, Eli Lilly/Daiichi Sankyo; consultancy fees from Merck. Dr James reports receiving institutional research grant and honoraria from AstraZeneca, Eli Lilly, Merck, and Bristol-Myers Squibb and being an advisory board member for AstraZeneca, Eli Lilly, and Merck. Dr Becker reports receiving research grant from Johnson & Johnson, Bayer, and Regado Biosciences; honoraria from Johnson&Johnson, Regado Biosciences, and Daiichi-Sankyo; being a consultant for AstraZeneca, Regado Biosciences, Johnson&Johnson, and Daiichi-Sankyo. Dr Goodman reports receiving Research grant support and speaker/consulting honoraria from: AstraZeneca, Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, Lilly, Merck, Sanofi-Aventis. Dr Husted reports being an advisory board member for AstraZeneca, Bristol-Myers Squibb, Pfizer, and Bayer; research support from GlaxoSmithKline, Pfizer, and Sanofi-Aventis. Dr Katus declares consulting and lecture fees from AstraZeneca. Dr Steg has received research grant support from Servier; and speaking/consulting honoraria from Astellas, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Eisai, Medtronic, MSD, Pfizer, Roche, Sanofi-Aventis, The Medicines Company, AstraZeneca, Servier, Merck, Otsuka, and he is a Stockholder Aterovax. KW Mahaffey has received research grant support from Eli Lilly, Johnson&Johnson, Portola, Sanofi-Aventis, The Medicines Company, Schering-Plough, Bayer, Bristol-Myers Squibb, Daiichi Sankyo; and speaking/consulting honoraria from Bristol Myers Squibb, Daiichi Sankyo, Johnson&Johnson, Sanofi-Aventis, Schering-Plough, AstraZeneca, Eli Lilly. Dr Storey reports receiving research grant from AstraZeneca, EliLilly/Daiichi-Sankyo and Merck; research support from Accumetrics; honoraria from AstraZeneca, Eli Lilly/Daiichi-Sankyo, Merck, Novartis, The Medicines Company, Iroko, Sanofi-Aventis/Bristol-Myers Squibb, GlaxoSmithKline, Accumetrics, Medscape, and Eisai; and being a consultant for AstraZeneca, Merck, Novartis, Accumeterics, and Eisai. Dr Vintila reports receiving research grants from Sanofi-Aventis and Servier; consultant fees from Pfizer and Sanofi-Aventis; speaker fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Menamni, Merck, Novartis, Pfizer, Sanofi-Aventis, and Servier; and has advisory board membership with AstraZeneca, Novartis, Pfizer, Sanofi-Aventis, and Servier. Dr Santoso and Mrs Sun report having no relationship with the industry. Dr Horrow: employee of AstraZeneca and having equity ownership in AstraZeneca. Dr Wallentin reports receiving research grants from AstraZeneca, Merck/Schering-Plough, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline, and Schering-Plough; being a consultant for Merck/Schering-Plough, Regado Biosciences, Protola, CSL Behring, Athera Biotechnologies, Boehringer-Ingelheim, AstraZeneca, GlaxoSmithKline, and Bristol-Myers Squibb/Pfizer; lecture fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb/Pfizer, GlaxoSmithKline, Schering-Plough. Dr Harrington reports advisory board fees from Novartis, Portola Pharmaceutical, and Merck; consulting fees from AstraZeneca, Bristol-Myers Squibb, Merck, Novartis, Portola, and Sanofi-Aventis; honoraria/lecture fees from Eli Lilly, Merck, and AstraZeneca; grant support from AstraZeneca, Bristol-Myers Squibb, Portola Pharmaceutical, Merck, Novartis and The Medicines Company; travel support from AstraZeneca, Novartis, and Merck.
PY - 2012/9
Y1 - 2012/9
N2 - Background: Habitual smoking has been associated with increased platelet reactivity, increased risk of thrombotic complications and greater efficacy of clopidogrel therapy over placebo. In the PLATO trial, ticagrelor compared to clopidogrel in patients with acute coronary syndromes (ACS) reduced the primary composite end point of vascular death, myocardial infarction and stroke, without increasing overall rates of major bleeding. We evaluated the results in relation to smoking habits. Methods: Interactions between habitual smokers (n = 6678) and in ex/nonsmokers (n = 11,932) and the effects of randomized treatments on ischemic and bleeding outcomes were evaluated by Cox regression analyses. Results: Habitual smokers had an overall lower risk profile and more often ST-elevation ACS. After adjustment for baseline imbalances, habitual smoking was associated with a higher incidence of definite stent thrombosis (adjusted HR, 1.44 [95% CI, 1.07-1.94]); there were no significant associations with other ischemic or bleeding end points. The effects of ticagrelor compared to clopidogrel were consistent for all outcomes regardless of smoking status. Thus, there was a similar reduction in the primary composite end point for habitual smokers (adjusted HR, 0.83 [95% CI, 0.68-1.00]) and ex/nonsmokers (adjusted HR, 0.89 [95% CI, 0.79-1.00]) (interaction P =.50), and in definite stent thrombosis for habitual smokers (adjusted HR, 0.59 [0.39-0.91]) and ex/nonsmokers (adjusted HR, 0.69 [95% CI, 0.45-1.07]) (interaction P =.61). Conclusions: In patients hospitalized with ACS, habitual smoking is associated with a greater risk of subsequent stent thrombosis. The reduction of vascular death, myocardial infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is consistent regardless of smoking habits.
AB - Background: Habitual smoking has been associated with increased platelet reactivity, increased risk of thrombotic complications and greater efficacy of clopidogrel therapy over placebo. In the PLATO trial, ticagrelor compared to clopidogrel in patients with acute coronary syndromes (ACS) reduced the primary composite end point of vascular death, myocardial infarction and stroke, without increasing overall rates of major bleeding. We evaluated the results in relation to smoking habits. Methods: Interactions between habitual smokers (n = 6678) and in ex/nonsmokers (n = 11,932) and the effects of randomized treatments on ischemic and bleeding outcomes were evaluated by Cox regression analyses. Results: Habitual smokers had an overall lower risk profile and more often ST-elevation ACS. After adjustment for baseline imbalances, habitual smoking was associated with a higher incidence of definite stent thrombosis (adjusted HR, 1.44 [95% CI, 1.07-1.94]); there were no significant associations with other ischemic or bleeding end points. The effects of ticagrelor compared to clopidogrel were consistent for all outcomes regardless of smoking status. Thus, there was a similar reduction in the primary composite end point for habitual smokers (adjusted HR, 0.83 [95% CI, 0.68-1.00]) and ex/nonsmokers (adjusted HR, 0.89 [95% CI, 0.79-1.00]) (interaction P =.50), and in definite stent thrombosis for habitual smokers (adjusted HR, 0.59 [0.39-0.91]) and ex/nonsmokers (adjusted HR, 0.69 [95% CI, 0.45-1.07]) (interaction P =.61). Conclusions: In patients hospitalized with ACS, habitual smoking is associated with a greater risk of subsequent stent thrombosis. The reduction of vascular death, myocardial infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is consistent regardless of smoking habits.
UR - http://www.scopus.com/inward/record.url?scp=84866325657&partnerID=8YFLogxK
U2 - 10.1016/j.ahj.2012.06.005
DO - 10.1016/j.ahj.2012.06.005
M3 - Article
C2 - 22980299
AN - SCOPUS:84866325657
VL - 164
SP - 334-342.e1
JO - American Heart Journal
JF - American Heart Journal
SN - 0002-8703
IS - 3
ER -