Selecting Antiplatelet Agents for Diabetics With Acute Coronary Syndrome

Patients with acute coronary syndrome (ACS) rely on platelet P2Y₁₂-receptor antagonists and aspirin to reduce the risk of serious adverse cardiovascular events. While the current American College of Cardiology Foundation/American Heart Association guidelines endorse clopidogrel, prasugrel, or ticagrelor in ACS patients who have undergone percutaneous coronary intervention (PCI), the blanket recommendation fails to differentiate among the drugs or patient types.

Many cardiologists and pharmacists are particularly concerned about clopidogrel, especially when it is prescribed for patients with diabetes. An editorial published in the September 2014 of the Journal of the American College of Cardiology provided a concise yet thorough overview of this issue.

Clopidogrel’s antiplatelet effect varies considerably among individuals. Patients with higher levels of on-treatment platelet reactivity (OTR) measured by multiple platelet assays—a test that is not yet used routinely in clinical settings—have an increased risk of thrombotic events after PCI. Many questions remain regarding elevated OTR, and the answers will probably elude pharmacists until clopidogrel’s unique characteristic that causes response variability is identified.

The editorial, authored by Matthew J. Price, MD, walked readers through an overview of clopidogrel’s biotransformation in its active metabolite, as well as CYP2C19’s role in partially reducing that metabolite’s activity.

Dr. Price continued on to discuss diabetes, another risk factor for impaired clopidogrel response that is independent of CYP2C19 genotype. He described a study published in the same issue that reported clopidogrel’s impaired antiplatelet effect in diabetics is due primarily to lower levels of active drug compared with normal controls, rather than inherent platelet problems. In other words, diabetes alters clopidogrel’s pharmacokinetic profile.

Since diabetic patients with unstable coronary artery disease have an elevated risk of recurrent cardiovascular events, clopidogrel may not be the best choice for these patients. Instead, Dr. Price said that diabetic patients with ACS might do better on ticagrelor. Similarly, evidence suggests that prasugrel may be preferred in diabetic patients with ACS undergoing PCI. The caveat is that patients must have acceptable bleeding risks and no contraindications.

Dr. Price also noted that each of the 3 drugs presents unique issues, including cost, adverse effects, and bleeding risk. He concludes by reminding health care professionals that “P2Y₁₂-receptor inhibition is not a panacea: diabetes is strongly associated with an increased risk of ischemic events in ACS, irrespective of the P2Y₁₂ antagonist used.”