Long-Term Aspirin Therapy

Abstract & Commentary

Synopsis: Long-term treatment with aspirin is associated with a progressive diminution in platelet sensitivity to the drug.

Source: Pulcinelli FM, et al. J Am Coll Cardiol. 2004;43:979-984.

The long-term benefits of aspirin therapy in patients after acute coronary syndromes (ACS) are poorly understood, especially in light of newer oral antiplatelet agents. Thus, Pulcinelli and associates from Rome studied 150 ACS patients taking aspirin (100 or 330 mg/d) and compared these to 80 matched patients taking ticlopidine. In vitro platelet aggregation tests were done serially before and during antiplatelet therapy for 24 months. In vitro tests of platelet aggregation were significantly prolonged at 2 months compared to baseline after aspirin but progressively declined at 6, 12, and 24 months. At 24 months, about 40% of patients had returned to their baseline values. The effect of aspirin was not related to whether they were on 100 or 330 mg/d. The effect of ticlopidine was constant over the 24 months. Pulcinelli et al concluded that long-term treatment with aspirin is associated with a progressive diminution in platelet sensitivity to the drug.

Comment by Michael H. Crawford, MD

Although this is an in vitro study with no clinical outcome data, the results are interesting and support newer practices in treating ACS patients. The progressive decline in aspirin’s effect on platelets to a point where almost half are unresponsive at 24 months may partly explain the recurrence of major adverse cardiac events in patients on aspirin long term. Also, these observations support the results of CREDO, which suggested that clopidrogrel should be added for long-term platelet inhibition in post-ACS patients since there was no decrease in the effect of ticlopidine in this study. Should aspirin be stopped after 6 months or a year to reduce the risk of bleeding, other GI toxicity, and possibly stroke? Probably not, as not all patients respond to adenosine diphosphate inhibitors. In this study, 9% showed no effect of ticlopidine, and other studies have shown up to 15% resistance to clopidrogrel. Thus, at this point, long-term antiplatelet therapy after ACS should include aspirin at 75 mg/d and clopirdrogrel 75 mg/d. The duration of such treatment is unclear but may be indefinite.

Dr. Crawford is Professor of Medicine, Associate Chief of Cardiology for Clinical Programs, University of California, San Francisco.