Abstract 11942: Influence of Smoking Status on the Frequency f High Platelet Reactivity During Prasugrel and Clopidogrel Therapy: Analysis From the Paradox Study
Background: Analyses from clinical outcome studies including CAPRIE, CURE, CREDO, CLARITY-TIMI 28, CHARISMA, and CURRENT demonstrate that nonsmokers experience less or no benefit from clopidogrel (Clop) treatment as compared with smokers, who have a robust treatment benefit. Evidence supports the concept of a threshold for high on-treatment platelet reactivity (HPR) that may be used to stratify risk for ischemic/thrombotic events in PCI-treated patients. The effect of smoking status on the frequency of HPR in Clop- and prasugrel (Pras)-treated patients has never been examined in a prospective study. We hypothesized that Pras is associated with a lower frequency of HPR than Clop regardless of smoking status and that the highest frequency of HPR occurs in Clop nonsmokers.
Methods: PARADOX was a prospective, double-blind, placebo-controlled study of 56 nonsmokers and 54 smokers with stable CAD on aspirin therapy randomized to Clop (75 mg qd for 10 d) or Pras (10 mg qd for 10 d) and crossed-over after a 14 day washout period. The frequency of HPR was assessed using VerifyNow (VN)-P2Y12 assay and VASP-PRI using the following cut-off values PRU >235 and VASP-PRI >50% (post-hoc: PRU>208 and VASP-PRI >60%).
Results: Based on logistic regression analyses using all 4 HPR definitions, the incidence of HPR was significantly lower for Pras compared to Clop regardless of smoking status (p<0.05 for all treatment comparisons). The highest frequency of HPR occurred in Clop nonsmokers (Table).
Conclusion: PARADOX demonstrates that Pras therapy is associated with a significantly lower incidence of HPR compared to Clop regardless of smoking status. Clop nonsmokers have a high frequency of HPR and this may provide a mechanism for the results of analyses from six randomized trials demonstrating less or no clinical benefit of Clop treatment in nonsmokers.
- © 2012 by American Heart Association, Inc.