ACS Vocabulary: Are Patients Nonresponsive or Resistant to Therapy?

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a cornerstone acute coronary syndrome (ACS) treatment to prevent thrombotic events after coronary stent placement.

Up to 40% of ACS and percutaneous coronary intervention patients respond inadequately to clopidogrel therapy, but most respond to other P2Y12 inhibitors, such as prasugrel and ticagrelor.

Clopidogrel activation’s cytochrome P450 enzyme reactions can delay onset of action and cause drug interactions that reduce its efficacy.

An article published ahead-of-print in the Journal of Pharmacy Practice details antiplatelet inhibition variability in patients taking clopidogrel.

One problem with discussions about platelet therapy in cardiac patients is vocabulary. Some clinicians talk about resistance: an antiplatelet regimen’s failure to prevent a thrombotic cardiovascular event.

However, a recurrent ischemic event may not be due to actual biological resistance. Some clinicians now advocate measuring actual patient response and calling patients with unexpectedly low antiplatelet responses “nonresponders.”

The most common platelet inhibition test is the VerifyNow P2Y12 assay, which identifies high on-treatment platelet response in platelet reactivity units, with a value >230 being indicative of insufficient response.

Patients who take prasugrel or ticagrelor may achieve a greater response after stenting for ACS.

· Prasugrel is contraindicated in patients with a previous history of stroke or transient ischemic attack and should be used cautiously in patients older than 75, except those with a history of coronary artery disease or diabetes.

· Ticagrelor is dosed twice daily; metabolized by the CYP3A4 enzyme, which is often a precipitant of interactions; and increases the risk of dyspnea, ventricular pauses, elevated serum creatinine, and elevated uric acid levels.

Clopidogrel is overwhelmingly preferred for platelet inhibition, but prasugrel and ticagrelor have a place in therapy in targeted populations.

High on-treatment platelet response testing may be warranted prior to discharge in patients with proximal left anterior descending stents or left main stents, as these patients are at higher risk of thrombus-induced mortality.

The study authors reminded clinicians that patient nonresponsiveness may also be due to poor adherence.