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Slow initial response to clopidogrel linked to low final response

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – In treating acute coronary syndromes, a slow response to clopidogrel in the first hour of administration predicts a low response at 24 hours and high post-treatment platelet reactivity, according to a new report.

The clinical implications of this finding, however, are unclear, the researchers write in the February 23rd Journal of the American College of Cardiology.

“Fast inhibition of platelet aggregation is important in the setting of acute coronary syndromes and percutaneous coronary intervention, but its association with the final degree of inhibition is not well established,” Dr. Gilles Montalescot, from Pitie-Salpetriere Hospital, Paris, and coauthors explain.

To investigate, the researchers conducted a post-hoc analysis of data from the randomized, dose-ranging ALBION study. In 96 patients given clopidogrel loading doses of either 300, 600 or 900 mg, the researchers analyzed maximal platelet aggregation (MPA) as induced by adenosine diphosphate, and the changes in MPA over the 24 hours after the loading dose.

A slow clopidogrel response was defined as a change in MPA of <10% in the first hour. A fast response was an MPA change of 10% or more by the end of the hour. A low response was defined as <10% change at 24 hours after loading. Finally, post-treatment platelet reactivity was defined as the lowest MPA value as measured at 8 points during the 24-hour period.

Overall, 55% of patients were slow responders. These patients were significantly more likely than fast responders to have a low response at 24 hours (p < 0.0001).

Slow responders were also more likely to have high post-treatment platelet reactivity (p < 0.0001) and to have slower and lower decreases in the PAC-1 and P-selective inflammatory markers, as well as slower and lower decreases in vasodilator-stimulated phosphoprotein.

A body mass index of 25 or higher and non-smoking status were predictive of slower and lower clopidogrel responses, the report indicates. As the clopidogrel loading dose increased, there was a trend toward faster onset of platelet inhibition.

“Slow clopidogrel response is a reliable indicator of low clopidogrel response in acute coronary syndrome patients, but whether early detection and correction of slow clopidogrel response are clinically relevant remains to be shown,” the authors conclude.

Reference:

J Am Coll Cardiol 2010;55:815-822.