Halting Clopidogrel in First Year Following Acute MI Hazardous

PARIS, France—In patients with acute myocardial infarction (MI) who are prescribed clopidogrel, stopping the antiplatelet within the first year of treatment more than doubles the risk of death or nonfatal MI, according to results of a large registry study presented August 29, at the European Society of Cardiology Congress 2011.

But discontinuation was less likely in patients who received PCI, reported Adam D. Timmis, MD, of Barts and the London School of Medicine and Dentistry (London, United Kingdom). The study was published simultaneously online ahead of print in the European Heart Journal.

Investigators used the British Myocardial Ischemia National Audit Project (MINAP) registry and the General Practice Research Database (GPRD) to track clopidogrel adherence and outcomes in 7,543 UK patients discharged home from 2003 through 2009 after an NSTEMI or STEMI. Overall, 4,650 of the patients received a clopidogrel prescription within 3 months, comprising 69% of the NSTEMI patients and 63% of the STEMI patients. The odds of receiving clopidogrel were substantially higher in patients managed with PCI during hospital admission than those who did not receive coronary intervention (OR 6.19; 95% CI 4.80-7.99).

By 1 year, the percentages of patients still on clopidogrel were roughly equal for NSTEMI (53%) and STEMI (54%). However, these rates were much lower than what was seen for the same patient groups in terms of statin use (84% and 89%, respectively).

Discontinuation of clopidogrel was more common in patients aged greater than 80 years, those who had a bleeding event after leaving the hospital, and those who underwent CABG. Discontinuation was less likely in patients who underwent PCI (table 1).

Table 1. Factors Associated with Clopidogrel Discontinuation Within 12 Months

Patients

Adjusted HR

95% CI

Age > 80 Years

1.50

1.16-1.94

Bleeding Events

1.34

1.03-1.73

CABG

1.82

0.99-3.35

PCI

0.72

0.63-0.83


In the first year after discharge, 18.15 patients per 100 person-years died or suffered nonfatal MI. Discontinuation of clopidogrel was associated with an increased risk of death and MI compared with never being prescribed the drug (adjusted HR 1.45; 95% CI 1.22-1.73) and remaining on clopidogrel (adjusted HR 2.62; 95% CI 2.17-3.17).

“Is there a higher rate of death or MI among patients who stop taking clopidogrel because they are more prone to thrombotic events, or due to a healthy user bias?” Dr. Timmis asked. “We did not investigate, but we assume that’s because the patient’s platelet reactivity abruptly re-increases and predisposes them to thrombotic events. One theory is that sicker patients tend to stop taking treatment,” but that theory does not account for the mismatch in discontinuation rates between statins and clopidogrel, he noted.

In the EHJ paper, the researchers write, “Our data show that discontinuation of clopidogrel during the first 12 months is common, particularly in older patients, and associated with an increased risk of death or recurrent MI.”

They stress that the study does not establish a causal association between halting clopidogrel and death or MI. “Nonetheless, discontinued prescribing of clopidogrel ahead of guideline recommendations must be treated with caution, and strategies to promote the appropriate use of secondary prevention treatment in this high-risk group of patients are required,” Dr. Timmis and colleagues conclude.

 


Source:
Boggon R, van Staa TP, Timmis A, et al. Clopidogrel discontinuation after acute coronary syndromes: frequency, predictors and associations with death and myocardial infarction—a hospital registry-primary care linked cohort (MINAP–GPRD). Eur Heart J. 2011; Epub ahead of print.

 

 

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Disclosures
  • The study was funded by AstraZeneca.
  • Dr. Timmis reports serving as a committee member of the National Institute of Cardiac Outcomes Research.
  • GPRD has received funding from various universities, contract research organizations, and pharmaceutical companies.

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