Smoking and antiplatelet agents – smoke and mirrors or something more?

Many antiplatelet therapies are prodrugs that require metabolic activation.  It has been hypothesized that smoking may activate this metabolic conversion for some antiplatelets (i.e. clopidogrel) more than others (i.e. prasugrel and ticagrelor).  In this systematic review and meta-analysis, the authors identified 9 randomized controlled trials of clopidogrel, prasugrel, or ticagrelor which examined outcomes among subgroups of smokers and non-smokers.  In the studies of clopidogrel, smokers on clopidogrel saw a 25% reduction in the primary composite outcome of cardiovascular death, MI, and stroke compared with patients in the control group (RR 0.75, 95% CI 0.67 – 0.83).  However, in non-smokers there was only an 8% reduction in the primary end point (RR 0.92, 95% CI 0.87 – 0.98).  Similarly, greater risk reduction was observed for smokers on ticagrelor or prasugrel when compared to clopidogrel while risk reduction was similar for all three drugs in non-smokers.

Conclusion:

It is unclear if the relative effect of antiplatelet therapies in smokers simply reflects differences in baseline clinical risk or differences in the metabolic activation of antiplatelet drugs.  Study of antiplatelet therapies stratified by patient cardiovascular disease risk may provide further insight.

  • Gagne JJ, Bykov  K, Choudhry NK, et al.  Effect of smoking on comparative efficacy if anti platelet agents: systematic review, meta-analysis, and indirect comparison.  BMJ 2013;347:f5307 doi:10.1136/bmj.f5307 (Pulished 17th September 2013).