Additional Evidence of Clustering of Cardiovascular Events Following Cessation of Clopidogrel in Patients with ACS
- In multivariable analysis, including adjustment for total duration of clopidogrel treatment, the 0-90 day interval after stopping clopidogrel was associated with significantly increased risk of death/MI compared to the 91-360 day interval among a non-VA population. There was a similar trend of increased adverse events after stopping clopidogrel for various subgroups (women vs. men, medical therapy vs. percutaneous coronary intervention, stent type, and = or < 6 months of clopidogrel treatment).
- This clustering of adverse events was not present among patients stopping ACE-inhibitors, suggesting that the events are not a general effect of stopping medications.
- There was no association between the 91-360 day interval after stopping clopidogrel and adverse outcomes compared to patients remaining on clopidogrel.
A previous study of Veterans with acute coronary syndrome (ACS) demonstrated a nearly two-fold increase in the risk of death or acute myocardial infarction (MI) in the initial 90-day period following the cessation of clopidogrel. However, it is unknown whether or not the observations of a clustering of adverse events following clopidogrel cessation from this study, as well as indications from several other studies, can be generalized to broader ACS patient populations. Thus, this retrospective cohort study assessed the risk of adverse outcomes after stopping clopidogrel among 2,017 patients with ACS (acute MI or unstable angina) enrolled in a large, non-VA integrated healthcare system (Kaiser Permanente of Colorado) between 1/02 and 12/06. Rates of all-cause mortality or acute MI within one year after stopping clopidogrel were assessed among patients who did not have an event prior to stopping clopidogrel. To assess the association between time interval after stopping clopidogrel and risk of adverse events, investigators examined adverse events in the first 0-90 day interval after stopping clopidogrel compared with the 91-360 day interval.
- Specific reasons for stopping clopidogrel were unknown.
- As with any retrospective cohort study design, investigators could not confirm causality or completely exclude residual confounding.
- These findings are consistent with a possible rebound platelet hyper-reactivity after stopping clopidogrel; authors recommend additional platelet studies to confirm this effect. These results also confirm and extend previous findings and suggest an urgent need to develop strategies to attenuate this effect following the end of a prescribed clopidogrel treatment course.
Dr. Ho was supported by an HSR&D Career Development Award and is part of VA/HSR&D’s Ischemic Heart Disease Quality Enhancement Research Initiative (IHD-QUERI).
Ho P, Tsai T, Wang T, et al. Adverse Events after Stopping Clopidogrel in Post-Acute Coronary Syndrome Patients: Insights from a Large Integrated Healthcare Delivery System. Circulation: Cardiovascular Quality and Outcomes May 1, 2010,3(3):303-308.