LOS ANGELES, CA—In patients with acute coronary syndromes (ACS) treated with prasugrel, the incidence of high on-treatment platelet reactivity depends on the type of platelet function test used, according to a study presented November 5, 2012, at the American Heart Association Scientific Sessions. The results indicate that high platelet reactivity with the new thienopyridine can be overcome by reloading, but may be associated with an increased short-term ischemic risk.  

Stephen A. O’Connor, MD, of the Institute de Cardiologie Hôpital Pitié-Salpêtrière (Paris, France), and colleagues analyzed 388 patients treated with prasugrel (60 mg loading dose plus 10 mg daily for at least 2 days) after PCI for an ACS. Patients had at least 2 different platelet function techniques performed simultaneously. Those who had 1 or more assay type demonstrating high on-treatment platelet reactivity according to the prespecified definitions were identified (n = 33; 8.5%):

• VASP ≥ 50% by flow cytometry
• P2Y12 reaction units (PRU) ≥ 235 using VerifyNowP2Y12 (Accumetrics, San Diego, CA)
• Residual platelet aggregation (RPA) ≥ 46.2% using light transmission aggregometry (LTA)  

Platelet Function Dependent on Several Factors  

The majority of patients had only 1 of the 3 assays demonstrating high on-treatment platelet reactivity (69.7%) and one-third of patients (30.3%) had at least 2 different platelet function techniques concordantly demonstrating high platelet reactivity. Only 3 (9.1%) patients had 3 concordant tests.

Factors associated with high on-treatment platelet reactivity were increased BMI (P = 0.03), acute stent thrombosis presentation (P < 0.0001) and testing in the acute phase (< 15 days; P < 0.0001).  

No therapeutic action was taken in 87.9% of cases. A repeat loading dose was administered in 4 cases with high on-treatment platelet reactivity defined by at least 2 tests; 3 became responders; and 1 patient required 3 loading doses over 3 days to respond. There was a stepwise increase in ischemic cardiovascular events at 1-month follow-up ranging from normal responders (n = 355; 0.8%) to patients with only 1 test (8.7%) to patients with at least 2 concordant tests demonstrating high platelet reactivity (30%; P < 0.0001 across all groups).  

At 6 months, patients with high on-treatment platelet reactivity had a higher incidence of death, MI, or stent thrombosis compared with normal responders (18.2% vs. 3.1%; P < 0.002). In addition, patients with 2 or more concordant platelet function tests had a higher rate of cardiovascular events than those with discordant tests, and both of these groups had a higher rate than normal responders (30.0% vs. 13% vs. 3.1%; P < 0.001).  

“The predictive value of testing is increased by using multiple platelet function testing techniques,” Dr. O’Connor said, adding that, if possible, he would use all 3 tests to confirm high on-treatment platelet reactivity although not all hospitals have access to each of the testing modalities. He suggested that the defined cut-off for VASP might need to be raised to correlate better with the current consensus LTA and PRU thresholds.   

Study Details

Patients were mostly male (87.8%) with a mean age of 60.5 years. About one-third (29.4%) of the patients had diabetes and about two-thirds presented with STEMI (60.1%).  

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