JACC: Simple assay test identifies clopidogrel low responders

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While some patients may have genetic mutations that don't allow clopidogrel (Plavix, Bristol-Myers Squibb) to work effectively, genetic testing is not always an easy option. Researchers have determined that a simple assay specific test that identifies low platelet reactivity accurately predicts those at high risk of cardiovascular death following PCI, according to a study in the June issue of the Journal of the American College of Cardiology: Cardiovascular Interventions.

Soraya El Ghannudi, MD, and colleagues from the University of Strasbourg in France assessed 461 unselected patients with a vasodilator-stimulated phosphoprotein flow cytometry test (VASP- FCT). The VASP-FCT is a new assay specific to the P2Y12 adenosine diphosphate receptor-pathway, upon which clopidogrel acts.

In this test, platelet activation is expressed as a platelet reactivity index (PRI). Lower PRI values are associated with higher antiplatelet efficacy. Researchers set a cutoff PRI threshold of 61 percent, based on receiver-operator characteristic curve analysis.

At follow-up of a mean of nine months of 98 percent of the urgent and nonurgent patients from the prospective registry, investigators found that those with a low-response to clopidogrel, as determined by the test, had higher cardiac mortality rates and possible and total stent thrombosis.

The hazard ratio (HR) of a low response to clopidogrel as an independent predictor of cardiac death was 4.00. Other HRs included: drug-eluting stent: 5.73; C-reactive protein: 1.01; and creatinine clearance 0.95.

"The deleterious impact of low response to clopidogrel on cardiovascular death was significantly higher in patients implanted with drug-eluting stents," the authors wrote.

Ghannudi and colleagues detailed some advantages of the VASP assay compared with platelet aggregometry:

  • Specificity of the P2Y12 signaling;
  • No need for a pretreatment measurement;
  • Lack of interference with aspirin or glycoprotein IIb/IIIa antagonists;
  • Standardization of the procedure;
  • Measurement on whole blood; and
  • Stability of the measurement up to 48 hours.

They also emphasized that the cutoff threshold for VASP tests have not be uniform and that their threshold of 61 percent clearly identifies those at high risk of cardiovascular death and other events following PCI.

In an accompanying editorial, Sotirios Tsimikas, MD, and Gregor Leibundgut, MD, from the University of California, San Diego, speculated whether there is even a need for genetic testing with the approval of prasugrel and, in the future, ticagrelor and other P2Y12 antagonists.

"Although prasugrel is associated with better efficacy and also more bleeding, ticagrelor demonstrated reduced cardiovascular mortality with similar bleeding rates. With clopidogrel becoming available as a generic drug soon, cost issues might ultimately drive the debate about when and if to genotype or measure platelet function," they said.

They also listed ongoing studies that look at various agents, dosages and assay tests, which perhaps will resolve some of these issues.