Abstract 3732: The Influence of Aspirin Dose With or Without Clopidogrel on Efficacy and Safety in the CHARISMA Trial
The optimal dose of ASA, especially in the setting of long-term preventative therapy, remains controversial as evidenced by the 4-fold range of doses routinely utilized, and may be particularly important in patients receiving long-term dual antiplatelet therapy.
Methods:The CHARISMA trial included 15,603 patients with documented, or at high risk of developing atherothrombotic disease, randomized to clopidogrel 75mg daily or placebo. All patients received protocol-mandated daily, low-dose ASA (75mg to 162mg), with the actual dose at the discretion of the local investigator. Median follow-up was 28 months. The primary efficacy endpoint was the composite of CV death, MI or stroke, and the primary safety endpoint GUSTO severe/moderate bleeding.
Results:At randomization, 7,188 individuals received daily ASA doses <100mg (75– 81mg), 4,961 received 100mg, and 3,454 received >100mg (150–162mg). Overall, ASA dose had no significant influence on efficacy, with the trend favoring lower doses (<100mg −6.7%, 100mg −7.3%, >100mg −7.6%). Similarly, no dose-effect was found for bleeding (<100mg −3.3%, 100mg −2.6%, >100mg −3.5%). In patients randomized to clopidogrel, concomitant treatment with >100mg ASA daily was associated with significantly worse efficacy (8.4% vs 6.4% p=0.01) and a trend towards greater bleeding (4.4% vs 3.5%, p=0.08) than those receiving lower ASA doses.(Figure⇓)
Conclusion: Preventative ASA monotherapy between 75mg and 162mg daily appears to be equally efficacious and safe with lower doses tending to provide the greatest efficacy and safety. Daily ASA doses >100mg, when used with clopidogrel resulted in worse outcomes and greater bleeding risk.