title: Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome.
abstract: BACKGROUND
  It is unknown whether patients are at increased short-term risk for adverse events following clopidogrel cessation.
  
  
  OBJECTIVE
  To assess the rates of adverse events after stopping treatment with clopidogrel in a national sample of patients with acute coronary syndrome (ACS).
  
  
  METHODS
  Retrospective cohort study of 3137 patients with ACS discharged from 127 Veterans Affairs hospitals between October 1, 2003, and March 31, 2005, with posthospital treatment with clopidogrel.
  
  
  METHODS
  Rate of all-cause mortality or acute myocardial infarction (AMI) after stopping treatment with clopidogrel.
  
  
  RESULTS
  Mean (SD) follow-up after stopping treatment with clopidogrel was 196 (152) days for medically treated patients with ACS without stents (n = 1568) and 203 (148) days for patients with ACS treated with percutaneous coronary intervention (PCI) (n = 1569). Among medically treated patients, mean (SD) duration of clopidogrel treatment was 278 [corrected] (169) [corrected] days and death or AMI occurred in 17.1% (n = 268) of patients, with 60.8% (n = 163) of events occurring during 0 to 90 days, 21.3% (n = 57) during 91 to 180 days, and 9.7% (n = 26) during 181 to 270 days after stopping treatment with clopidogrel. In multivariable analysis including adjustment for duration of clopidogrel treatment, the first 90-day interval after stopping treatment with clopidogrel was associated with a significantly higher risk of adverse events (incidence rate ratio [IRR], 1.98; 95% confidence interval [CI], 1.46-2.69 vs the interval of 91-180 days). Similarly, among PCI-treated patients with ACS, mean (SD) duration of clopidogrel treatment was 302 [corrected] (151) [corrected] days and death or AMI occurred in 7.9% (n = 124) of patients, with 58.9% (n = 73) of events occurring during 0 to 90 days, 23.4% (n = 29) during 91 to 180 days, and 6.5% (n = 8) during 181 to 270 days after stopping clopidogrel treatment. In multivariable analysis including adjustment for duration of clopidogrel treatment, the first 90-day interval after stopping clopidogrel treatment was associated with a significantly higher risk of adverse events (IRR, 1.82; 95% CI, 1.17-2.83).
  
  
  CONCLUSIONS
  We observed a clustering of adverse events in the initial 90 days after stopping clopidogrel among both medically treated and PCI-treated patients with ACS, supporting the possibility of a clopidogrel rebound effect. Additional studies are needed to confirm the clustering of events after stopping clopidogrel, including associations with cardiovascular mortality and reasons for stopping clopidogrel, as well as to determine the mechanism of this phenomenon, and to identify strategies to reduce early events after clopidogrel cessation.
authors.affiliation: Denver VA Medical Center, Denver, Colorado 80220, USA.
authors.forename: P Michael
authors.initials: PM
authors.lastname: Ho
authors.forename: Eric D
authors.initials: ED
authors.lastname: Peterson
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: David J
authors.initials: DJ
authors.lastname: Magid
authors.forename: Stephan D
authors.initials: SD
authors.lastname: Fihn
authors.forename: Greg C
authors.initials: GC
authors.lastname: Larsen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Jesse
authors.forename: John S
authors.initials: JS
authors.lastname: Rumsfeld
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D002423:Cause of Death; D000077144:Clopidogrel; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016012:Poisson Distribution; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D028761:Withholding Treatment
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine