SAN FRANCISCO—Time for platelet function to return to baseline reflected the extent of platelet inhibition at 24 hours post-loading dose, and those treated with prasugrel required a longer time for recovery compared with clopidogrel, according to a scientific poster displayed Nov. 8 at the 23rd annual Transcatheter Cardiovascular Therapeutics (TCT) conference.
Prasugrel (Effient, Eli Lilly/Daiichi Sankyo) was associated with a faster onset of platelet inhibition compared with clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis), which may result in longer times for platelet P2Y12 receptor function to recover following drug cessation after loading dose administration, hypothesized Isabell Bernlochner, MD, of the Herzzentrum Muenchen in Munich, Germany, and colleagues. Thus, the aim of the the study was to assess the time to recovery of platelet function in patients with coronary artery disease following administration of a prasugrel or clopidogrel loading dose.
The researchers defined the recovery of platelet function after the thienopyridine loading dose as occurring on the first day that VerifyNow (Accumetrics) P2Y12 reaction units (PRU) were <60 below pre-drug values and remained in this range.
Assessing 21 patients, Bernlochner and colleagues looked at the percentage of patients who recovered over time (three, five, seven, nine and 11 days) following 30 mg or 60 mg of prasugrel or 600 mg of clopidogrel with aspirin by a measurement of PRU. They also evaluated the relationship between the inhibition of platelet function at 24 hours post-loading dose to time of recovery.
In the study population, 10 patients received a loading dose of 60 mg of prasugrel, six patients received 30 mg of prasugrel and five patients received 600 mg of clopidogrel.
Bernlochner and colleagues reported that prior to the administration of any drug, mean PRUs were 337.6, 308.2 and 323 for prasugrel 60 mg, prasugrel 30 mg and clopidogrel 600 mg, respectively. At 24 hours, post-loading dose, mean PRUs were lowest for prasugrel 60 mg (32.5), followed by prasugrel 30 mg (70) and clopidogrel 600 mg (193).
Of note, no patient treated with either loading dose of prasugrel showed platelet aggregation values above the high on-treatment platelet reactivity (HPR) cut-off values for any platelet function assays, whereas two patients treated with clopidogrel exhibited a status of HPR with the VerifyNow and Light Transmission Aggregometry assays.
Also, the researchers found that the recovery of platelet function over time in patients with CAD occurred earlier in patients treated with clopidogreal compared with either loading dose of prasugrel.
- Clopidogrel 600 mg took three to seven days;
- Prasugrel 30 mg took seven days; and
- Prasugrel 60 mg took seven to nine days.
Bernlocher et al concluded that platelet inhibition 24 hours after loading dose predicted the time point of platelet function return to baseline, and less inhibition resulted in a quicker return to baseline and greater inhibition results in longer return to baseline.