Adverse events after stopping clopidogrel in post-acute coronary syndrome patients: Insights from a large integrated healthcare delivery system.
BACKGROUND
A prior study from the Veterans Health Administration found a clustering of cardiovascular events after clopidogrel cessation. We sought to confirm and expand these findings.


RESULTS
This was a retrospective cohort study of 2017 patients with acute coronary syndrome discharged on clopidogrel from an integrated health care delivery system. Rates of all-cause mortality or acute myocardial infarction (MI) within 1 year after stopping clopidogrel were assessed among patients who did not have an event before stopping clopidogrel. Death/MI occurred in 4.3% (n=71) of patients. The rates of death/MI were 3.07, 1.62, 0.70, and 0.95 per 10 000 patient-days for the time intervals of 0 to 90, 91 to 180, 181 to 270, and 271 to 360 days after stopping clopidogrel. In multivariable analysis, the 0- to 90-day interval after stopping clopidogrel was associated with higher risk of death/MI (incidence rate ratio, 2.74; 95% confidence interval, 1.69 to 4.44) compared with 91- to 360-day interval. There was a similar trend of increased events after stopping clopidogrel for various subgroups (women versus men, medical therapy versus percutaneous coronary intervention, stent type, and > or =6 months or <6 months of clopidogrel treatment). Among patients taking clopidogrel but stopping ACE inhibitor medications, the event rates were similar in the 0- to 90-day versus the 91- to 360-day interval (2.67 versus 2.91 per 10 000 patient-days; P=0.91).


CONCLUSIONS
We observed a clustering of adverse events in the 0 to 90 days after stopping clopidogrel. This clustering of events was not present among patients stopping ACE inhibitors. These findings are consistent with a possible rebound platelet hyper-reactivity after stopping clopidogrel and additional platelet studies are needed to confirm this effect.
Ho
P Michael
PM
Denver VA Medical Center, CO, USA. michael.ho@coloradooutcomes.org <michael.ho@coloradooutcomes.org>
Tsai
Thomas T
TT
Wang
Tracy Y
TY
Shetterly
Susan M
SM
Clarke
Christina L
CL
Go
Alan S
AS
Sedrakyan
Art
A
Rumsfeld
John S
JS
Peterson
Eric D
ED
Magid
David J
DJ
D054058:Acute Coronary Syndrome / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology* / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000077144:Clopidogrel; D019033:Delivery of Health Care, Integrated; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D010351:Patient Discharge; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014481:United States; D028761:Withholding Treatment
D000806:Angiotensin-Converting Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine