Atlanta, GA - Smokers derive more benefit from combination antiplatelet therapy than nonsmokers, a retrospective analysis of the Clopidogrel for the Reduction of Events during Observation (CREDO) trial suggests. Reporting substudy findings during a poster session at the American College of Cardiology 2006 Scientific Sessions, Dr Kiran Saraff (Gill Heart Institute, Lexington, KY) told heartwire that while poorer outcomes following PCI in smokers is well established—believed due to increased platelet reactivity—the interaction of smoking status with dual antiplatelet therapy has not been studied.

Dr Kiran Saraff

"Despite being retrospective, this study clearly shows that smoking and antiplatelet drugs do have an interaction over and above all the other risk factors such as hypertension, history of MI, and so forth," Saraff commented. "We were not overly surprised by this. The adverse outcomes are known in smokers compared with nonsmokers, but aspirin plus clopidogrel, and whether they offer an incremental benefit, have not been studied in smokers before."

Smokers benefit, for a change

Saraff and colleagues compared rates of death, MI, and urgent target vessel revascularization (TVR) at 28 days and rates of death, MI, or stroke at one year in relation to smoking status in 2116 participants in the CREDO study. At 28 days, the rate of death, MI, and urgent TVR was higher in smokers than in nonsmokers taking aspirin alone, but lower in smokers than in nonsmokers taking combination therapy. At one year, a similar pattern was seen, with significantly lower event rates in smokers taking dual antiplatelet therapy than in smokers taking aspirin only, whereas among nonsmokers, event rates were similar regardless of whether they were taking clopidogrel plus aspirin or aspirin alone.

"Smokers appear to derive greater benefit from dual antiplatelet therapy in the long-term following PCI," the authors conclude.

"There's probably a mechanistic involvement here," Saraff elaborated to heartwire. "Smokers tend to have decreased clopidogrel metabolism and therefore they may have higher bioavailability of the drug, compared with nonsmokers."

Saraff emphasized, "We shouldn't draw too much in the way of conclusions from a retrospective analysis of a substudy, but this is interesting and hypothesis-generating and should be tested prospectively. If confirmed, then yes, we would have to define which population subgroups are more likely to benefit from combination antiplatelet therapy as opposed to just prescribing it to everybody."