Low-Dose Prasugrel Effective in Elderly Heart Patients

June 10, 2013

By Will Boggs, MD

NEW YORK (Reuters Health) Jun 10 - A 5-mg dose of prasugrel provides adequate platelet inhibition in very elderly patients with stable coronary artery disease, pharmacodynamic data show.

"From previous studies we know that elderly patients have a higher risk of bleeding complications, and may therefore not tolerate too effective platelet inhibition, and the 10-mg dose of prasugrel is not recommended for very elderly (>75 years)," Dr. David Erlinge from Lund University, Lund, Sweden told Reuters Health.

"In our study, we found that the 5-mg dose of prasugrel had a less pronounced effect in the very elderly compared to the 10-mg dose, but still better effect than clopidogrel."

The 155 patients in the phase 1b trial were all volunteers who had experienced an acute coronary syndrome in the past and had used clopidogrel before, Dr. Erlinge said. They were either between the ages of 45 and 65 (mean, 56), or they were older than 75 (mean, 79).

Patients were treated for 12 days during each of the three crossover treatment periods, with either clopidogrel 75 mg, prasugrel 5 mg, or prasugrel 10 mg.

The median maximal platelet aggregation (MPA) response to prasugrel 5 mg in the very elderly group (58%) was noninferior to the 75th percentile of MPA response to prasugrel 10 mg in the non-elderly group (52%), because the upper bound of the confidence interval (9%) was below the prespecified 15% margin, the researchers reported in a paper released to news organizations by the Journal of the American College of Cardiology on June 5. The paper is not online yet.

The antiplatelet effect was significantly lower and the high on-treatment platelet reactivity rates were significantly higher with prasugrel 5 mg in very elderly patients than with prasugrel 10 mg in non-elderly patients.

In contrast, prasugrel 5 mg showed significantly greater antiplatelet effect than clopidogrel 75 mg in very elderly patients, as did prasugrel 10 mg in non-elderly patients.

Bleeding-related adverse events were similarly frequent in older and younger patients. As for the drug regimens, bleeding rates were similar with prasugrel 5 mg and clopidogrel 75 mg and significantly higher with prasugrel 10 mg.

"The findings indicate that 5-mg dose could be a more appropriate dose of prasugrel for the very elderly, reducing bleeding complications but still maintaining a better platelet inhibition than clopidogrel with fewer poor responders," Dr. Erlinge concluded.

"Additional randomized, controlled clinical trials are necessary to verify the clinical relevance of these results, particularly in acute coronary syndrome patients undergoing percutaneous coronary intervention," the authors note.

In the meantime, Dr. Erlinge says he might favor prasugrel 5 mg particularly for patients at high risk of being poor responders to clopidogrel, i.e., diabetics, obese patients, and those with certain CYP2C19-variants - along with patients whose platelet function tests show a poor response to clopidogrel, or those with re-infarction despite clopidogrel treatment.

Daiichi Sankyo Company, Ltd. and Eli Lilly and Company funded the study. Four of the 16 authors (including Dr. Erlinge) reported various relationships with Daiichi Sankyo and/or Eli Lilly, and Eli Lilly employed seven of the authors.

SOURCE: http://bit.ly/fb2fgy

J Am Coll Cardiol 2013.


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