There is a dose- and time-dependent variability in response to clopidogrel as measured by optical platelet aggregometry in response to ADP (Figs. 11 and 12) (58-61). Of interest is that although not designed to evaluate clinical outcomes, an intriguing finding in a study by Muller et al. (59) was that 2 patients (of 105 tested) developed subacute stent thrombosis, and both met the definition of clopidogrel nonresponse. An additional report correlated anginal class to platelet inhibition and found that patients with higher anginal class on presentation had less inhibition of platelet aggregation after loading with 450 mg of clopidogrel (62).
More recently, the laboratory measure of nonresponse to clopidogrel was correlated to clinical outcomes in patients who underwent primary PCI for STEMI (63). In those who received stents (n = 60), a loading dose of 300 mg of clopidogrel was given immediately after PCI and 75 mg daily for 3 mo. Platelet function tests were performed with turbidi-metric analysis after stimulation with ADP (5 pmol/L) and epinephrine (10 pmol/L), as
24 hours 5 days
Fig. 11. Monitoring of platelet aggregation in 96 patients undergoing elective coronary stenting before and after loading dose of300 mg of Clopidogrel followed by 75 mg daily. Clopidogrel resistance was defined as baseline aggregation (%) minus posttreatment aggregation (%) < or = 10% in response to 5 pmol/L of ADP (58).
well as with separate assays of platelet function using a CPA. Patients were divided into quartiles of inhibition of platelet aggregation (platelet aggregation compared with baseline platelet aggregation), with the first quartile considered nonresponders (d 6 aggregation of103 ± 8% compared with baseline). Although the study population was small, the data strongly suggest that there is individual variability in response to clopidogrel in the setting of PCI after STEMI and more broadly that clopidogrel resistance may be a marker for increased risk of recurrent cardiovascular events (Fig. 13).
Finally, the ALBION study will provide evidence for the correct loading dose of clopidogrel. This open-label study compares three regimens of loading dose (300, 600, and
Recurrent ACS, Ml, Stent Thrombosis, or Peripheral Arterial Occlusion (%)
Was this article helpful?