Specialist groups issue clinical alert to guide clopidogrel prescribers

Mylotarg withdrawn from market

Two cardiology groups released a clinical alert to guide doctors prescribing clopidogrel after the FDA added a boxed warning to the label about genetic variations that affect the drug's efficacy.

The FDA estimates that 2% to 14% of patients poorly metabolize clopidogrel (Plavix). Although there is increasing information about specific genetic variations that might affect metabolism, the agency says there is not sufficient evidence to develop specific recommendations related to genetic testing in patients.

In light of the FDA warning, the American College of Cardiology (ACC) Foundation and the American Heart Association (AHA) issued a statement outlining key issues to consider and recommendations for practice. The statement says that:

  • Evidence-based guidelines from the ACC, AHA or other professional societies for using antiplatelet therapies should remain the foundation of care. If clopidogrel is prescribed, health care providers should ensure that patients take it as prescribed.Clinicians must be aware that in certain patients with either acute or chronic coronary artery disease, genetic variability in response to clopidogrel can affect its inhibition of platelet function.Careful clinical judgment, including weighing the risks and benefits, is needed in considering all therapies. The new boxed warning points out that for clopidogrel, if there is a lack of efficacy, the outcome could be fatal.Results from ongoing clinical trials in large groups of patients will provide more information about the predictive value of genetic testing and better inform the role genotyping might play in personalizing medicine and optimizing outcomes.Genetic testing to determine if a patient is a “poor metabolizer” may be considered before starting clopidogrel therapy in patients believed to be at moderate or high risk for poor outcomes, such as patients undergoing elective high-risk percutaneous coronary intervention procedures.Using alternative antiplatelet therapies or altering the dosing of clopidogrel may be reasonable options in patients who experience an adverse event while taking clopidogrel and have been taking the drug as prescribed.

The statement authors cautioned that patients currently taking clopidogrel should not stop the drug unless advised by their clinician.

The American Academy of Family Physicians, the Society for Cardiovascular Angiography and Interventions and the Society for Thoracic Surgeons have also endorsed the recommendations, which will appear July 20 in the Journal of the American College of Cardiology and Circulation: Journal of the American Heart Association. The document will also be available on the ACC and AHA websites.