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Ticagrelor results consistent regardless of smoking status
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Among patients with ACS, reduction of vascular death, MI, stroke and stent thrombosis by ticagrelor compared with clopidogrel was consistent regardless of smoking status, according to a subgroup analysis of the PLATO trial.
Researchers reviewed results from the trial for the effects of ticagrelor (Brilinta, AstraZeneca) or clopidogrel (Plavix, Sanofi-Aventis) among 6,678 smokers and 11,932 former or nonsmokers to assess the effects on ischemic and bleeding outcomes.
Smoking was associated with definite stent thrombosis (adjusted HR=1.44; 95% CI, 1.07-1.94). There were no significant associations with other ischemic or bleeding endpoints.
Ticagrelor compared with clopidogrel offered consistent effects for outcomes of vascular death, MI and stroke regardless of whether the patient smoked (adjusted HR=0.83; 95% CI, 0.68-1.00) or was a former or nonsmoker (adjusted HR=0.89; 95% CI, 0.79-1.00), as well as for definite stent thrombosis for habitual smokers (adjusted HR=0.59; 95% CI 0.39-0.91) compared with former or nonsmokers (adjusted HR=0.69; 95% CI, 0.45-1.07).
Investigators said the “smoker’s paradox” accounts for habitual smokers presenting with ACS who are younger, with less CV risk than former or nonsmokers. After correcting for baseline characteristics, the risk for recurrence of CV events did not differ significantly between smokers and former or nonsmokers except for definite stent thrombosis, which was more common in smokers.
“Since ticagrelor is not dependent on metabolism for its activity, smoking should not influence its inhibitory effects,” the researchers wrote. “Thus, it might be expected that habitual smoking might reduce the treatment effect of ticagrelor compared to clopidogrel. However, we did not observe any significant interaction between smoking status and the relative efficacy of ticagrelor compared to clopidogrel.”
Perspective
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J.P. Reilly, MD, FSCAI
Smoking increases the risk and unfavorable consequences of heart disease, including stent thrombosis and MI. Some studies have suggested that clopidogrel may be more effective at inhibiting platelets in smokers than in nonsmokers. This analysis of the relative effectiveness of clopidogrel and ticagrelor in the PLATO trial revealed that smoking status did not matter. Ticagrelor maintained its superiority over clopidogrel among smokers, similar to the overall trial. It is unclear from this and other trials whether clopidogrel is more effective on platelet aggregation among smokers. But this analysis from PLATO suggests that smoking status should not be a determinant of which drug to recommend.
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