NEW YORK (Reuters Health) – In patients with chronic coronary artery disease, prasugrel overcomes high on-clopidogrel platelet reactivity more effectively than doubling the dose of clopidogrel, results of a prospective, randomized, crossover study suggest.

A “substantial percentage” of patients on chronic clopidogrel therapy exhibit high platelet reactivity, with potentially harmful consequences, the study team notes in the October issue of the American Heart Journal.

“Strategies to optimize platelet inhibition in such patients are not clear,” but may include increasing the dose of clopidogrel or using a more potent P2Y12 inhibitor, such as prasugrel, explain Dr. Dimitrios Alexopoulos and colleagues from Patras University Hospital in Greece.

They investigated the relative antiplatelet effect of prasugrel 10 mg/day versus high-dose clopidogrel (150 mg/day) in patients with stable coronary artery disease who exhibited high platelet reactivity on chronic clopidogrel 75 mg/day.

Of 99 patients screened, 31 (31.3%) had high on-clopidogrel platelet reactivity and were enrolled in the study. For 14 days, they took either clopidogrel 150 mg/day or prasugrel 10 mg/day and then crossed over to the other treatment for 14 days. Platelet reactivity was assessed using the point-of-care assay VerifyNow from Accumetrics, Inc, of San Diego, California.

The study team found that the primary endpoint of platelet reactivity at the end of the two treatment periods was lower in patients receiving prasugrel than double-dose clopidogrel (least squares estimate, 148.1 and 219.8, respectively; P < 0.001).

The secondary endpoint of high on-treatment platelet reactivity was also lower with prasugrel than with clopidogrel (11.5% vs 46.3%; P = 0.003).

Dr. Alexopoulos and colleagues say three “important findings” emerge from this study.

First, up to one third of the population on chronic clopidogrel treatment may exhibit high platelet reactivity.

Second, doubling the clopidogrel dose in these patients is “ineffective in almost half of the cases.”

Third, prasugrel achieves a significantly higher platelet inhibition than double-dose clopidogrel in these patients.

By overcoming clopidogrel resistance, prasugrel “may confer a greater ischemic benefit, although with a potential for increased bleeding risk,” the authors note.

Prasugrel overcomes high on-clopidogrel platelet reactivity in chronic coronary artery disease patients more effectively than high dose (150 mg) clopidogrel

Reference:

Am Heart J 2011;162:733-739.