New Data Suggest Patient Smoking Habits Had No Impact on PLATO Study Findings of a Greater Reduction in Thrombotic CV Events with Ticagrelor vs. Clopidogrel
WILMINGTON, Del. (September 6, 2012) — AstraZeneca
James Ferguson, MD, Executive Director, Medical Affairs and Strategic Development, and Vice President for Global Medical Affairs, said, “This sub-analysis suggests that the clinical benefits of ticagrelor vs clopidogrel on thrombotic CV events shown in PLATO were not significantly affected by smoking status, and were similar in both smokers and non-smokers.”
Ticagrelor is indicated to reduce the rate of thrombotic CV events in patients with acute coronary syndrome (ACS: unstable angina [UA], non–ST-elevation myocardial infarction [NSTEMI], or ST-elevation myocardial infarction [STEMI]). In PLATO, ticagrelor has been shown to reduce the rate of a combined end point of CV death, myocardial infarction (MI), or stroke compared to clopidogrel. In PLATO, the difference between treatments was driven by CV death and MI with no difference in stroke. In patients treated with percutaneous coronary intervention (PCI), ticagrelor reduces the rate of stent thrombosis.
Ticagrelor has been studied in ACS in combination with aspirin. Maintenance doses of aspirin above 100 mg decreased the effectiveness of ticagrelor. Avoid maintenance doses of aspirin above 100 mg daily.
The sub-analysis was conducted because habitual smoking has been associated with increased platelet reactivity, increased risk of thrombotic complications and greater efficacy of clopidogrel therapy over placebo.
Specific data from this sub-analysis showed:
• Among the 18,610 patients with known smoking status at randomization in the PLATO study, 6,678 (36%) were reported as being habitual smokers and 11,932 (64%) were ex/non-smokers
• Habitual smokers had an overall lower risk profile and presented more often with ST-elevation MI
• After adjustment for baseline differences, 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 thrombotic CV events, regardless of smoking status.(1) 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/non-smokers (adjusted HR, 0.89 [95% CI, 0.79-1.00]) (interaction P=0.50), and in definite stent thrombosis for habitual smokers (adjusted HR, 0.59 [0.39-0.91]) and ex/non-smokers (adjusted HR, 0.69 [95% CI, 0.45-1.07]) (interaction P=0.61)
• There was no significant interaction between smoking habits and the effects of treatment on major bleeding or non-CABG related major bleeding. The adjusted hazard ratios for the rate of all PLATO-defined major bleeding for ticagrelor versus clopidogrel were 1.18 [95% CI, 0.98-1.43] in habitual smokers and 1.04 [95% CI, 0.92-1.18] in ex/non-smokers (interaction P=0.27). For non-CABG related major bleeding events the adjusted hazard ratios for ticagrelor versus clopidogrel were 1.22 [95% CI, 0.88-1.69] in habitual smokers and 1.35 [95% CI, 1.10 – 1.67] in ex/non-smokers (interaction P=0.59)
The conclusion of the sub-analysis of PLATO suggests results of ticagrelor versus clopidogrel were consistent for thrombotic cardiovascular (CV) events in patients with acute coronary syndrome (ACS) regardless of smoking status and that habitual smoking was associated with a greater risk of subsequent stent thrombosis.